Efficacy and Safety of Simtuzumab (SIM) With FOLFIRI as Second Line Treatment in Colorectal Adenocarcinoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy and Safety of Simtuzumab (SIM) With FOLFIRI as Second Line Treatment in Colorectal Adenocarcinoma (NCT01479465), a randomized phase 2 study. The primary outcome is Progression Free Survival (PFS).

2. Clinical Question

The clinical question is whether adding SIM to the same chemotherapy backbone is associated with a different time to progression or death in this population. The registry identifies a randomized, double-blind, placebo-controlled, parallel-group Phase 2 study. The Part B comparisons are the dose-specific comparisons of interest: placebo versus SIM 200 mg and placebo versus SIM 700 mg. The Part A SIM 700 mg group is recorded separately and is much smaller than the Part B groups; it is not one of the sponsor-reported Part B hazard-ratio comparisons.

The study also listed overall survival (OS) and objective response rate (ORR) as secondary outcomes. Numerical ORR results are posted, while numerical OS results are not reported in the registry record. The record does not establish why the study was terminated, how the original sample size was chosen, or what analysis procedures beyond those explicitly named were planned. The results therefore address the posted comparisons and outcomes, not every possible question about the study or its conduct.

3. Trial Design

This was a Phase 2, randomized, double-blind, placebo-controlled, parallel-group study sponsored by Gilead Sciences. The registry lists enrollment of 266 and a terminated status. The study began in 2011-12, and primary completion is recorded as 2014-10. The reason for termination is not reported in the registry record.

Participants in the treatment groups received SIM or placebo followed by FOLFIRI through intravenous infusion on Days 1 and 15 of each 28-day treatment cycle. Treatment was described as continuing until disease progression or unacceptable toxicity. The Part B groups were FOLFIRI plus placebo, FOLFIRI plus SIM 200 mg, and FOLFIRI plus SIM 700 mg. A separate Part A group received FOLFIRI plus SIM 700 mg. The registry describes the Part A group separately from the Part B comparisons.

The primary outcome was PFS, with a timeframe from randomization up to 27 months. The primary analysis population included participants who were randomized and received at least 1 dose of study drug. The registry says PFS was analyzed using Kaplan-Meier estimates. Sponsor-reported comparisons for the two Part B SIM groups used a Log Rank method and reported hazard ratios with 95% confidence intervals and p-values.

Randomization and masking are important design features because they are intended to limit systematic differences and expectations that could influence comparisons. The registry does not report further details about the randomization procedure, allocation concealment, masking procedures, stratification factors, or the original statistical design assumptions. Nor does it report the reason the study was terminated. These omissions limit how fully the conduct and planned analysis can be reconstructed from the record alone.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: 358 participants were screened.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full Analysis Set included participants who were randomized and received at least 1 dose of study drug.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: All randomized participants were analyzed.

6. Primary Endpoint

The registry lists the primary outcome as Progression Free Survival (PFS), measured over Randomization up to 27 months.

Progression-free survival measures the time from randomization until the first recorded event of disease progression or death from any cause. It is a time-to-event outcome: participants may experience the event at different times, while others may not have a recorded event during the period in which they are followed. The registry specifies that the PFS timeframe was randomization up to 27 months and that Kaplan-Meier estimates were used.

PFS is used in trials where the timing of progression or death is a central outcome. Unlike a simple count of participants who have progressed by one selected date, a time-to-event analysis can use information about when events occurred and can account for participants whose event time is not observed within follow-up through censoring. In general, censoring means the event time is not known beyond the last relevant observation; the registry record does not describe the censoring rules or how missing follow-up was handled in this study.

The reported median PFS is the estimated time by which the Kaplan-Meier curve reaches the point where half of the analyzed population is estimated to have experienced the event. It is not an average and does not describe each participant’s experience. A median and its confidence interval also do not, by themselves, establish that groups differ. The sponsor’s hazard-ratio comparisons summarize relative event rates over follow-up under the analysis model and are accompanied by confidence intervals and p-values. Interpretation depends on the comparison’s group ordering and event coding, which are not further detailed in the registry record.

7. Results Posted in the Registry

• FOLFIRI + Placebo (Part B) vs FOLFIRI + SIM 200 mg (Part B): hazard ratio 1.45 (95% CI 1.01–2.06), reported p = 0.040 (as reported in the registry).
• FOLFIRI + Placebo (Part B) vs FOLFIRI + SIM 700 mg (Part B): hazard ratio 1.32 (95% CI 0.92–1.89), reported p = 0.104 (as reported in the registry).

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Objective Response Rate (ORR)

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • FOLFIRI + SIM 700 mg (Part A): 9.1% (1/11) versus 10.0% (8/80) on control; risk difference -0.9 percentage points (95% CI -19.1 to 17.3), risk ratio 0.91 (0.13–6.59); unadjusted two-proportion z-test p = 0.925.
  • FOLFIRI + SIM 200 mg (Part B): 5.9% (5/85) versus 10.0% (8/80) on control; risk difference -4.1 percentage points (95% CI -12.4 to 4.1), risk ratio 0.59 (0.20–1.72); unadjusted two-proportion z-test p = 0.327.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between FOLFIRI + SIM 700 mg (Part A) and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between FOLFIRI + SIM 200 mg (Part B) and the control. The interval gives the range of effects that remain compatible with the data.

The registry lists overall survival and objective response rate as secondary outcomes, but the numerical results posted for secondary outcomes include ORR and do not include numerical OS results. ORR estimates vary across the listed groups, and their confidence intervals are wide, particularly for the small Part A group. The posted ORR comparisons are unadjusted recalculations from summary counts; they are not sponsor-reported analyses. They should be treated as descriptive and exploratory rather than as confirmatory evidence.

Secondary outcomes can provide context about other aspects of the study, but they do not replace the prespecified primary endpoint. A response proportion and a time-to-event outcome measure different features of the clinical course. Agreement or apparent disagreement between them is not necessarily a contradiction. The primary PFS result remains the central outcome identified by the registry, while secondary measures may help describe the broader pattern without resolving uncertainty in the primary comparison.

Unadjusted secondary findings carry less weight because multiple outcomes or comparisons can create more opportunities for apparently notable results by chance. The registry does not report a multiplicity strategy, so the family of tests and any control of false-positive risk cannot be assessed from the record. Numerical OS results are not reported in the registry record, which prevents assessment of whether that outcome’s pattern aligns with PFS. These limitations counsel against treating a secondary comparison as independent confirmation of the primary finding.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Overall Survival (OS)
• Objective Response Rate (ORR)

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is a time-to-event measure. Each participant contributes information about the time from randomization to disease progression or death, or, if neither event is recorded during observed follow-up, information up to the last point at which the participant’s status is known. General time-to-event analyses are useful when follow-up duration varies and when not every participant has an observed event by the end of observation. The registry describes Kaplan-Meier estimates for PFS, but does not report detailed censoring rules, follow-up completeness, or the handling of missing outcome information.

What does a Kaplan-Meier median represent?

In general, a Kaplan-Meier curve estimates the proportion of participants who remain free of the event over time while incorporating censored observations. The median is the time at which the estimated event-free proportion reaches one half. It is a summary of the curve, not a measure of the typical individual participant’s full experience and not an average of all observed event times. The registry reports median PFS in months with 95% confidence intervals for each group.

A median alone may not capture the whole pattern of event times. Two groups can have similar medians but differ elsewhere along their curves, or have different medians while uncertainty remains substantial. The curve and the confidence interval help readers see the uncertainty and the timing pattern, but the underlying individual event and censoring data are not available in the registry record.

How should the hazard ratios be read?

The sponsor reports hazard ratios from Log Rank comparisons for placebo versus each Part B SIM dose. A hazard ratio compares event rates over follow-up under the analysis approach; it is not a ratio of median PFS times. A value of 1 represents equal hazards under the ratio definition. Values on either side of 1 indicate different relative hazards, but direction depends on which group’s hazard is in the numerator and how events are coded. Although the comparison labels list placebo first and SIM second, the registry does not give further detail on the coding or reference-group convention. The reported estimates should therefore be quoted with their stated comparison rather than assigned an unqualified directional interpretation.

The Log Rank method is a general procedure for comparing time-to-event distributions between groups. It uses event timing across follow-up rather than comparing only the median values. The registry identifies Log Rank as the method for the reported analyses, but does not report details such as stratification, model covariates, proportional-hazards checks, or the precise procedure used to calculate confidence intervals.

What do confidence intervals and p-values add?

A confidence interval expresses statistical uncertainty around an estimate. For a hazard ratio, a 95% confidence interval indicates a range of values compatible with the data and the analysis under the method’s assumptions; it is not a guarantee that the true value lies inside that particular interval. An interval including 1 is compatible with no difference in hazard under the ratio definition, while an interval excluding 1 indicates that the interval does not include that reference value. This does not by itself determine the importance of the estimate.

A p-value measures how unusual the observed data, or data more extreme, would be under a specified null hypothesis and analysis. It is not the probability that the null hypothesis is true, nor does it quantify the chance that a result is due to chance. The reported p-values are 0.040 for placebo versus SIM 200 mg and 0.104 for placebo versus SIM 700 mg. The registry does not report whether or how the analyses accounted for multiple comparisons. If several hypotheses are tested, general statistical practice recognizes that the chance of at least one small p-value can increase unless the analysis plan addresses multiplicity.

Why is the analysis population relevant?

The registry defines the primary Full Analysis Set as participants who were randomized and received at least 1 dose of study drug. This makes the reported population narrower than all enrolled participants may be, depending on who received treatment. General intention-to-treat principles commonly aim to preserve randomized group assignment, but the registry does not say that the posted analysis was a full intention-to-treat analysis or describe exclusions after randomization. The precise participant flow and reasons for any exclusions are not reported in the registry record.

These method details matter because time-to-event estimates depend on the group definition, event ascertainment, and censoring. Randomization supports comparisons by reducing systematic baseline differences on average, while double blinding is intended to limit differences in care or outcome assessment related to treatment knowledge. Neither feature removes uncertainty, missing data, or the need for transparent analysis decisions. The record provides the endpoint definition, analysis population, Kaplan-Meier approach, and sponsor-reported Log Rank comparisons, but does not report many additional design and analysis details.

11. Confidence Intervals and Precision

Precision concerns how much uncertainty surrounds an estimate. The 95% confidence intervals for median PFS are relatively broad in some groups, particularly the Part A SIM 700 mg group, which included 11 participants and had a median of 5.7 months with an interval from 1.8 to 10.0 months. The Part B placebo group had a median of 5.8 months with an interval from 4.9 to 9.0 months; the SIM 200 mg group had a median of 5.4 months with an interval from 3.4 to 5.6 months; and the SIM 700 mg group had a median of 5.5 months with an interval from 4.0 to 7.1 months.

The hazard-ratio interval for placebo versus SIM 200 mg runs from 1.01 to 2.06 around the estimate of 1.45. For placebo versus SIM 700 mg, the interval runs from 0.92 to 1.89 around the estimate of 1.32. The latter interval includes 1, and both intervals span a range of possible effect sizes. Thus, neither point estimate should be read as exact. The registry’s confidence intervals describe uncertainty under the analyses used; they do not account for unreported design features or potential biases.

Confidence intervals for the medians and hazard ratios answer different questions and are not interchangeable. Overlap or non-overlap of separate group median intervals is not a substitute for the sponsor’s direct comparison test. Similarly, a confidence interval that excludes the null value does not establish clinical importance. Precision should be considered together with the study population, analysis choices, and the status of the trial. The registry does not report enough detail to evaluate all sources of uncertainty, including missing follow-up and the full analysis plan.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size illustrations are planning calculations based on the observed effect, not the trial’s original design calculations. For PFS, the figures are total events required, not participants per arm. For ORR, the figures are participants per arm. The planning assumptions are a two-sided significance level 0.05, equal allocation between the two arms, and a normal approximation; the effect to detect is the stated fraction of the observed effect. The trial’s own original sample-size assumptions are not reported in the registry record.

The 80% power column describes the number of events or participants needed, under those assumptions, for an 80% chance of detecting the specified effect if that effect were the true one. The 90% power column gives the corresponding requirement for a 90% chance. These are planning concepts, not guarantees for any particular study. For example, the PFS comparison of placebo with SIM 200 mg lists 228 total events for 80% power and 305 for 90% power when planning for 100% of the observed effect. The corresponding figures for placebo versus SIM 700 mg are 408 total events and 546 total events. For the ORR comparison of placebo with SIM 200 mg, the illustration lists 676 participants per arm for 80% power and 905 participants per arm for 90% power when planning for 100% of the observed effect.

Planning for 75% or 50% of the observed effect requires more events or participants than planning for the full observed effect. Smaller effects are harder to distinguish from random variation, so more information is needed to detect them with the same target power. These calculations are not observed power: they do not describe the probability that the completed trial detected an effect, and they do not replace the sponsor’s reported analyses.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

d is the total number of events needed (Schoenfeld's formula) with 1:1 allocation and proportional hazards.

Worked calculation for this trial

1. Hazard ratio HR = 1.450, so ln(HR) = 0.3716.
2. d = 4 × (1.96 + 0.842)² / [ln(1.450)]² = 227.4, rounded up to 228 events in total for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
hr <- 1.45                              # observed hazard ratio
events_needed <- function(power, frac = 1) ceiling(round(4 * (z_a + qnorm(power))^2 / log(hr^frac)^2, 6))   # Schoenfeld, 1:1 allocation
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: events = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(events_needed(0.80, f), big.mark = ","), format(events_needed(0.90, f), big.mark = ",")))

# Simulation: given d total events under proportional hazards, events in the treatment arm are Binomial(d, hr / (1 + hr)).
# The score (log-rank type) statistic is (D1 - d / 2) / sqrt(d / 4).
set.seed(1479465)
d    <- events_needed(0.80)
reps <- 20000
D1 <- rbinom(reps, d, hr / (1 + hr))
z  <- (D1 - d / 2) / sqrt(d / 4)
cat(sprintf("Simulated power with %s events: %.3f (%d replicates)\n", format(d, big.mark = ","), mean(abs(z) > z_a), reps))

Output from running the code

100% of observed effect: events = 228 (80% power), 305 (90% power)
 75% of observed effect: events = 405 (80% power), 542 (90% power)
 50% of observed effect: events = 910 (80% power), 1,218 (90% power)
Simulated power with 228 events: 0.805 (20000 replicates)

The simulation uses the fact that, with d events in total and proportional hazards, the number of events in the treatment arm is binomial. It is an approximation that conditions on the total number of events, and it should land close to the target power.

14. Analyses Reported by the Sponsor

The registry reports sponsor analyses for the two Part B comparisons using a Log Rank method. For placebo versus SIM 200 mg, the reported hazard ratio is 1.45, with a 95% confidence interval from 1.01 to 2.06 and p = 0.040. For placebo versus SIM 700 mg, the reported hazard ratio is 1.32, with a 95% confidence interval from 0.92 to 1.89 and p = 0.104. Both are labelled as superiority analyses in the registry.

Those sponsor-reported results take precedence over any simple recalculation from posted summary statistics. For time-to-event data, a hazard ratio and its test generally depend on event times, censoring, and analysis details that cannot be reconstructed from group medians alone. The registry record does not provide individual participant data or all model details, so the reported analyses cannot be independently reproduced from the posted medians and confidence intervals alone.

The sponsor’s results should be read as the reported inferential comparisons, with attention to their confidence intervals and the lack of registry detail about multiplicity and analysis specifications. The absence of a reported adjustment does not establish whether one was or was not used outside the information in the record; the adjustment procedure is not reported in the registry record.

15. Multiplicity, Missing Data and Analysis Populations

The registry reports two sponsor analyses of the primary endpoint, one comparing placebo with SIM 200 mg and the other comparing placebo with SIM 700 mg. It does not report how multiplicity was addressed across these comparisons, across the primary and secondary outcomes, or across any other analyses. When several hypotheses are examined, general statistical practice recognizes that interpreting each p-value as if it were the only test can overstate the evidence. Without a stated plan, the intended error-rate control cannot be evaluated.

Other parts of the statistical plan are also not reported in the registry record. These include the original sample-size justification, any planned interim analyses, whether the primary analysis was stratified or adjusted, details of the hazard-ratio model and its assumptions, and the approach to missing outcome data. The reason for termination is not reported, so the record does not establish whether termination was related to efficacy, safety, recruitment, operational considerations, or another cause. No such reason should be inferred from the status alone.

The primary population is defined as randomized participants who received at least 1 dose of study drug. The registry does not provide participant flow details sufficient to assess exclusions, treatment discontinuation, or completeness of follow-up. It also does not report how censoring was handled or whether sensitivity analyses were conducted. These details can affect Kaplan-Meier and hazard-ratio results, especially if follow-up or outcome observation differs across groups.

Randomization and double blinding are features that support fair comparisons, but they do not answer these reporting questions. The record identifies the main endpoint, analysis population, and named statistical methods; it does not supply a complete protocol or statistical analysis plan. Conclusions should therefore remain bounded by the analyses and detail actually recorded.

16. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: anaemia (9.1%), atrial fibrillation (9.1%), abdominal pain (9.1%), sepsis (9.1%), diabetic ketoacidosis (9.1%).

The registry reports serious adverse events for the Part B groups in 27 of 80 participants receiving FOLFIRI plus placebo, 24 of 85 receiving FOLFIRI plus SIM 200 mg, and 17 of 84 receiving FOLFIRI plus SIM 700 mg. In Part A, serious adverse events were reported for 4 of 11 participants receiving FOLFIRI plus SIM 700 mg. These are counts of affected participants as recorded, not counts of every serious event.

The listed serious adverse event terms each appear with a reported frequency of 9.1%: anaemia, atrial fibrillation, abdominal pain, sepsis, diabetic ketoacidosis, and electrolyte imbalance. The registry does not provide further detail in the record on the number of events per participant, severity grading, attribution to study treatment, or timing. The recorded counts should not be interpreted as establishing that treatment caused an event or as a complete comparison of safety across groups.

Other adverse events affected 76 of 80 participants in the placebo group, 80 of 85 in the SIM 200 mg group, 79 of 84 in the SIM 700 mg group, and 11 of 11 in Part A. Death counts are not reported in the registry record. Safety comparisons require context on exposure duration, ascertainment, and event definitions, which is not fully available in the posted information.

17. What the Result Does, and Does Not, Mean

The posted record describes a Phase 2 randomized comparison of SIM plus FOLFIRI with placebo plus FOLFIRI in participants with metastatic KRAS-mutant colorectal adenocarcinoma following a first-line oxaliplatin- and fluoropyrimidine-containing regimen. It reports PFS medians and sponsor hazard-ratio analyses for the Part B dose groups. Those results are estimates with uncertainty, not definitive descriptions of what would occur for every participant or in other populations.

The results do not establish a causal mechanism or explain why the study was terminated. The status alone does not reveal the reason for termination. Nor do the results support claims about populations outside the eligibility description, other treatment settings, or outcomes that are not numerically reported. In particular, numerical OS results are not reported in the registry record, and the available record does not describe all analysis choices needed for a full independent assessment.

A p-value below a conventional threshold does not by itself establish the size, clinical importance, or reliability of a difference. A p-value above that threshold does not prove equivalence or absence of an effect. Confidence intervals show the range of values compatible with the data and assumptions, and the sponsor-reported hazard ratios should be considered with their intervals, comparison definitions, and the record’s missing methodological detail.

The figures therefore support a careful statistical reading of the recorded comparisons, not a treatment recommendation. They do not determine an individual’s care or establish what treatment should be used. The registry record is one source of trial information and should be understood within its population, outcomes, analysis scope, and reporting limitations.

18. Why This Trial Matters Statistically

This trial raises several important statistical issues in a compact setting. First, the primary outcome is time-to-event, so interpretation depends on event timing and censoring rather than only on the median values. Kaplan-Meier estimates and Log Rank comparisons address different aspects of that information, while the hazard-ratio coding and analysis details are not fully described in the registry record.

Second, the study has multiple dose comparisons and secondary outcomes. The record reports two sponsor comparisons for PFS but does not report a multiplicity procedure. This makes it important to distinguish a reported p-value from a complete account of confirmatory evidence. Secondary outcome estimates can be informative, but unadjusted comparisons have less evidential weight when several outcomes are considered.

Third, the registry’s Part A and Part B groups differ in size and in their place in the reported comparisons. The Part A SIM 700 mg group includes 11 participants, whereas the Part B arms include 80, 85, and 84 participants. Keeping these groups distinct helps prevent an unbalanced, separately recorded group from being mistaken for one of the main placebo-controlled comparisons.

Finally, termination status and unreported analysis details matter for interpretation. The reason for termination, original sample-size assumptions, missing-data procedures, and multiplicity strategy are not reported in the registry record. Recognizing these gaps is part of sound statistical reading: precise numerical estimates can be quoted, while the boundaries of what the record can establish remain explicit.

19. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The record leaves several trial-specific questions unanswered. The reason for the terminated status is not reported, so the circumstances and timing of the decision cannot be evaluated. The original sample-size justification and planned assumptions are also not reported in the registry record; the planning illustrations based on observed effects are not a substitute for that design information.

The primary analysis population is defined, but participant flow and the handling of participants who did not receive study drug or lacked outcome information are not detailed. The registry does not describe censoring rules, missing-data methods, follow-up completeness, or sensitivity analyses. These details are especially relevant for PFS because Kaplan-Meier estimates depend on the event and censoring information available over time.

The record identifies Log Rank analyses and gives sponsor-reported hazard ratios, confidence intervals, and p-values, but does not describe hazard-ratio coding, stratification, covariate adjustment, proportional-hazards assessment, or multiplicity handling. It also does not report numerical OS results. The reported safety information lacks further detail on event timing, exposure duration, attribution, and the number of repeated events per participant.

These are limitations of the information available in the registry record; they do not establish that the underlying trial lacked procedures or analyses. They do mean that conclusions should be restricted to the reported endpoints, populations, comparisons, and estimates.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Efficacy and Safety of Simtuzumab (SIM) With FOLFIRI as Second Line Treatment in Colorectal Adenocarcinoma — NCT01479465.
• Registry record last updated 2019-04-17; status last verified 2019-03.
• Results first posted 2019-04-17.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

23. Record Summary

NCT01479465 is a randomized, double-blind, placebo-controlled Phase 2 study of simtuzumab with FOLFIRI for metastatic KRAS-mutant colorectal adenocarcinoma after progression on a first-line oxaliplatin- and fluoropyrimidine-containing regimen. The registry lists enrollment of 266, study start in 2011-12, primary completion in 2014-10, and status as terminated.

The primary endpoint was PFS from randomization to disease progression or death, analyzed with Kaplan-Meier estimates in participants randomized and treated with at least 1 dose. Sponsor-reported Log Rank comparisons are recorded for placebo versus SIM 200 mg and placebo versus SIM 700 mg. ORR is also reported as a secondary outcome; numerical OS results and the reason for termination are not reported in the registry record.