Phase 2 AMG 386 in Comb. Paclitaxel for Subjects With Advanced Recurrent Epithelial Ovarian or Primary Peritoneal Cancer

Phase 2

Completed

• Conditions: Fallopian Tube Cancer; Ovarian Cancer; Primary Peritoneal Cancer
• Interventions: Drug: AMG 386; Drug: AMG 386 Placebo; Drug: Paclitaxel

• Registration Number: NCT00479817
• Lead Sponsor: Amgen

Brief Summary

This study is a phase 2, randomized, double-blind, placebo controlled, multi-center study to estimate the improvement in PFS (compared to control subjects) and evaluate the safety and tolerability of AMG 386 in combination with paclitaxel in the treatment of subjects with advanced recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer.

Primary Outcome Measure:

• Progression free survival (PFS)

Secondary Outcome Measures:

* Object Response Rate (ORR), duration of response (DOR). CA-125 response rate

* Safety and Tolerability

* Change and duration of change on blood levels of CA-125

Detailed Description

Primary Objective:

To estimate the treatment effect as measured by progression free survival (PFS) of subjects with recurrent ovarian cancer receiving AMG 386 (either 3 mg/kg or 10 mg/kg IV QW) in combination with paclitaxel (80 mg/m2 IV QW; 3 on/1 off)compared to subjects receiving paclitaxel (80 mg/m2 IV QW; 3 on/1 off) plus placebo

Secondary Objective(s):

* To evaluate the safety and tolerability of the combination regimen of AMG 386/paclitaxel

* To estimate other measures of treatment effect (by parameters other than PFS) of subjects receiving AMG 386 in combination with paclitaxel compared to subjects receiving paclitaxel plus placebo

* To evaluate the AMG 386 pharmacokinetics parameters (Cmax and Cmin ) when administered with paclitaxel in subjects with recurrent ovarian cancer

* To estimate the incidence of occurrence of anti-AMG 386 antibody formation

* To estimate the change and duration of change on blood levels of CA-125

* To evaluate the clinical benefit among subjects receiving AMG 386 10 mg/kg monotherapy after disease progression on paclitaxel

* To estimate the impact of AMG 386 on patient reported ovarian cancer specific symptoms and HRQoL using the FACT-O, the FACT-O ovarian cancer subscale (OCS), and the FACT-O 3-item (O1, O2, O3) cancer symptom specific subscale (OCS 3-item subscale)

Exploratory Objective(s):

* To explore the associations between progression free survival, objective response, CA-125, and continuous measures of tumor burden (the percentage change from baseline in the sum of the longest diameters of target lesions)

* To explore the pharmacodynamic (PD) response as assessed by changes in blood levels of angiogenic cytokines, tumor apoptosis, CA-125 and other markers

* To investigate the effects of genetic variation in drug metabolism, cancer genes and drug target genes on ovarian cancer and subject response to investigational product (separate informed consent)

* To explore the impact of AMG 386 on patient reported overall health status as measured by the EuroQoL (EQ-5D)

Hypothesis:

This study will provide an estimate and corresponding 2-sided 80% confidence interval with an approximate maximum half-width of 0.22 of the efficacy, as measured by the PFS hazard ratio of AMG 386 in combination with paclitaxel versus paclitaxel alone for 2 pooled dose groups of AMG 386 (10 mg/kg QW and 3 mg/kg QW) in combination with paclitaxel versus the paclitaxel plus placebo group.

Study Timeline

• Study First Submitted: 2007-05-24
• Study First Submitted QC: 2007-05-24
• Study First Posted: 2007-05-28
• Study Start: 2007-07-05
• Primary Completion: 2009-08-11
• Disposition First Submitted: 2015-10-29
• Disposition First Submitted QC: 2015-10-29
• Disposition First Posted: 2015-11-25
• Status Verified: 2019-12
• Study Completion: 2019-12-09
• Last Update Submitted: 2019-12-16
• Last Update Posted: 2019-12-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 161

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm B	AMG 386	Paclitaxel 80 mg/m2 IV QW (3 on/1 off) + AMG 386 3 mg/kg IV QW
Arm A	AMG 386	Paclitaxel 80 mg/m2 IV QW (3 on/1 off) + AMG 386 10 mg/kg IV QW
Arm C	AMG 386 Placebo	Paclitaxel 80 mg/m2 IV QW (3 on/1 off) + AMG 386 placebo
Arm B	Paclitaxel	Paclitaxel 80 mg/m2 IV QW (3 on/1 off) + AMG 386 3 mg/kg IV QW
Arm A	Paclitaxel	Paclitaxel 80 mg/m2 IV QW (3 on/1 off) + AMG 386 10 mg/kg IV QW
Arm C	Paclitaxel	Paclitaxel 80 mg/m2 IV QW (3 on/1 off) + AMG 386 placebo

Primary Outcome Measures

Name	Time	Method
Progression Free Survival	2 years

Secondary Outcome Measures

Name	Time	Method
Objective Response Rate	2 years
Change from baseline in blood levels of CA-125	2 years
AMG 386 Pharmacokinetic parameters	2 years
Modified RECIST/CA-125 Progression Free Survival	2 years
Time to Progression	2 years
Safety and Tolerability	2 years
Estimate of reduction in tumor burden	2 years
Incidence of AEs and significant laboratory changes	2 years
Duration of Response	2 years
Incidence of the occurence of AMG 386 Antibody formation	2 years
CA-125 Response Rate	2 years
Overall Survival	2 years
Time to Response	2 years
Time-adjusted area under the curve for PROs	2 years