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Ovarian Cancer Phase 3 Randomized NCT01204749

TRINOVA-1: Complete Statistical Analysis of AMG 386 in Ovarian Cancer

An independent statistical review of the randomized phase 3 TRINOVA-1 trial evaluating AMG 386 or placebo in combination with weekly paclitaxel chemotherapy for ovarian cancer, primary peritoneal cancer, and fallopian tube cancer.

ClinicalTrials.gov identifier: NCT01204749
Scope of this record

This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record.

1. Trial at a Glance

919
Enrollment
3
Phase
2
Treatment Arms
8 Months
Primary Endpoint Time Frame
FeatureTRINOVA-1
ConditionFallopian Tube Cancer; Ovarian Cancer; Primary Peritoneal Cancer
DesignRandomized, parallel assignment, quadruple masking
Primary purposeTreatment
SponsorAmgen
Study start2010-11
Primary completion date2013-03

2. Clinical Question

Population

Patients with ovarian cancer, primary peritoneal cancer, or fallopian tube cancer.

Intervention

AMG 386 combined with weekly paclitaxel chemotherapy.

Comparator

AMG 386 placebo combined with weekly paclitaxel chemotherapy.

Primary question

Does AMG 386 plus weekly paclitaxel affect progression-free survival compared with placebo plus weekly paclitaxel?

3. Trial Design

Allocation

Randomized

Masking

Quadruple masked

Model

Parallel assignment

Arms

Two treatment arms

ArmInterventions
AMG 386 armAMG 386 (drug) with weekly paclitaxel chemotherapy
Placebo armAMG 386 placebo with weekly paclitaxel chemotherapy

4. Endpoints

EndpointDefinitionTime Frame
Progression-Free SurvivalPrimary endpoint8 Months on average

5. Planned Analysis

The registry identifies Progression-Free Survival as the primary endpoint with an average time frame of 8 months. Results have not been posted on ClinicalTrials.gov.

For a randomized oncology trial with a progression-free survival endpoint, the statistical analysis would typically evaluate the time from randomization until disease progression or death. Common approaches include Kaplan-Meier estimation of the progression-free survival distribution, comparison of randomized groups using a time-to-event test, and estimation of relative treatment effects using a survival regression model.

Statistical interpretation: Because no primary endpoint analysis estimates are reported in the registry, the effect of AMG 386 on progression-free survival cannot be interpreted from the available registry information.

6. Statistical Methodology

Time-to-event analysis

Progression-free survival is a time-to-event endpoint. These analyses account for patients who have not experienced progression or death by their last assessment through censoring methods.

Randomized comparison

Randomization creates treatment groups intended to be comparable at baseline. The primary statistical comparison focuses on differences between randomized treatment assignments.

Survival model interpretation

When survival regression models are used, effect estimates summarize relative differences between groups while accounting for follow-up time and censoring.

7. Statistical Methods Explained

Why is progression-free survival analyzed differently from a simple response rate?

Progression-free survival includes both whether and when an event occurs. A time-to-event analysis uses information from follow-up duration and censoring.

Why does randomization matter?

Randomization reduces systematic differences between groups, allowing statistical comparisons to focus on the assigned intervention.

What does a Kaplan-Meier curve show?

A Kaplan-Meier estimate describes the proportion of patients remaining event-free over time while accounting for censored observations.

Why is censoring important?

Some participants may not have experienced progression or death at the time of analysis. Censoring allows their available follow-up information to contribute to the analysis.

8. Limitations

9. Why This Trial Matters Statistically

ConceptApplication
RandomizationComparison of AMG 386 and placebo treatment strategies
Time-to-event analysisProgression-Free Survival endpoint
CensoringRequired for patients without observed events at analysis
Clinical trial designPhase 3 parallel randomized masked study

10. Sources