Clinical Trials/NCT02718417

NCT02718417

Terminated

Phase 3

A RANDOMIZED, OPEN-LABEL, MULTICENTER, PHASE 3 STUDY TO EVALUATE THE EFFICACY AND SAFETY OF AVELUMAB (MSB0010718C) IN COMBINATION WITH AND/OR FOLLOWING CHEMOTHERAPY IN PATIENTS WITH PREVIOUSLY UNTREATED EPITHELIAL OVARIAN CANCER JAVELIN OVARIAN 100

Pfizer276 sites in 1 country998 target enrollmentMay 19, 2016

ConditionsOvarian Cancer

Interventionscarboplatin paclitaxel Avelumab

Drugscarboplatin paclitaxel Avelumab

Overview

Phase: Phase 3
Intervention: carboplatin
Conditions: Ovarian Cancer
Sponsor: Pfizer
Enrollment: 998
Locations: 276
Primary Endpoint: Progression-Free Survival (PFS) as Assessed by Blinded Independent Central Review (BICR)
Status: Terminated
Last Updated: 5 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is a Phase 3, open-label, international, multi-center, efficacy, and safety study of avelumab in combination with and/or following platinum-based chemotherapy. Eligible patients must have previously untreated, histologically confirmed Stage III-IV epithelial ovarian (EOC), fallopian tube cancer (FTC), or primary peritoneal cancer (PPC) and be candidates for platinum-based chemotherapy.

The primary purpose of the study is to demonstrate if avelumab given as single agent in the maintenance setting following frontline chemotherapy or in combination with carboplatin/paclitaxel is superior to platinum-based chemotherapy alone followed by observation in this population of newly diagnosed ovarian cancer patients.

Registry

clinicaltrials.gov

Start Date

May 19, 2016

End Date

May 16, 2019

Last Updated

5 years ago

Study Type

Interventional

Study Design

Parallel

Sex

Female

Investigators

Sponsor

Pfizer

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Histologically confirmed Stage III-IV epithelial ovarian, fallopian tube, or primary peritoneal cancer, including malignant mixed Müllerian tumors with high grade serous component
•Patients must be candidates for platinum based chemotherapy and previously untreated
•Patients must have completed a surgical debulking procedure, or be candidates for neoadjuvant chemotherapy
•Availability of an archival formalin fixed, paraffin embedded (FFPE) tumor tissue block or a minimum of 15 slides
•ECOG PS 0-1
•Adequate hematological, renal, and liver function

Exclusion Criteria

•Non epithelial tumors or ovarian tumors with low malignant potential (ie, borderline tumors) or mucinous tumors
•Prior systemic anti-cancer treatment for EOC, FTC, or PPC including prior immunotherapy with IL 2, IFN α, or anti PD 1, anti PD L1, anti PD L2, anti CD137, or anti cytotoxic T lymphocyte associated antigen 4 (anti CTLA 4) antibody (including ipilimumab), or any other antibody or drug specifically targeting T cell co stimulation or immune checkpoint pathways
•Patients for whom, in the opinion of the Investigator, there is clinical benefit to administer bevacizumab as a first-line treatment and for whom bevacizumab is approved and available in this setting.
•Cancer for which intraperitoneal cytotoxic chemotherapy is planned
•Active autoimmune disease (some exceptions include diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroidism not requiring immunosuppressive treatment)

Arms & Interventions

Arm A

Chemotherapy followed by observation

Intervention: carboplatin

Arm A

Chemotherapy followed by observation

Intervention: paclitaxel

Arm B

Chemotherapy followed by avelumab in maintenance

Intervention: carboplatin

Arm B

Chemotherapy followed by avelumab in maintenance

Intervention: paclitaxel

Arm B

Chemotherapy followed by avelumab in maintenance

Intervention: Avelumab

Arm C

Chemotherapy in combination with avelumab followed by avelumab in maintenance

Intervention: carboplatin

Arm C

Chemotherapy in combination with avelumab followed by avelumab in maintenance

Intervention: paclitaxel

Arm C

Chemotherapy in combination with avelumab followed by avelumab in maintenance

Intervention: Avelumab

Outcomes

Primary Outcomes

Progression-Free Survival (PFS) as Assessed by Blinded Independent Central Review (BICR)

Time Frame: Baseline to progression of disease or discontinuation from the study or death, whichever occurred first (maximum duration of 27 months)

BICR assessed PFS: Duration from randomization until disease progression or death. PFS data was censored on the date of the last adequate tumor assessment for participants who did not have an event (progression of disease or death), who started a new anti-cancer therapy prior to an event or for participants with an event after 2 or more missing tumor assessments. Progression as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1: as at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must have also demonstrated an absolute increase of at least 5 millimeters (mm). The appearance of one or more new lesions was also considered progression. Analysis was performed using Kaplan-Meier method.

Secondary Outcomes

Overall Survival(Baseline to discontinuation from the study or death, whichever occurred first (maximum duration of 27 months))
Progression-Free Survival (PFS) as Assessed by Investigator(Baseline to progression of disease or discontinuation from the study or death, whichever occurred first (maximum duration of 27 months))
Percentage of Participants With Objective Response as Assessed by Investigator(Baseline to progression of disease, start of new anti-cancer therapy or discontinuation from study or death, whichever occurred first (maximum duration of 27 months))
Percentage of Participants With Objective Response as Assessed by Blinded Independent Central Review (BICR)(Baseline to progression of disease, start of new anti-cancer therapy or discontinuation from study or death, whichever occurred first (maximum duration of 27 months))
Progression-Free Survival 2 (PFS2)(Baseline up to start of second subsequent treatment after first PD or discontinuation from study or death, which ever occured first (maximum duration of 27 months))
Change From Baseline in Vital Signs - Blood Pressure at Day 1 of Cycles 2, 3, 4 in Chemotherapy Phase; Days 1, 15 and 29 of Cycles 1 and 2 in Maintenance/ Observation Phase and at End of Treatment(Baseline, first 3 months of Chemotherapy Phase (CP): Day 1 of Cycles 2, 3 and 4 (each cycle 21 days); Maintenance/Observation Phase (MP/OP): Days 1, 15 and 29 of Cycles 1 and 2 (each cycle 42 days) and at end of treatment (up to 27 months))
Change From Baseline in Vital Signs - Pulse Rate at Day 1 of Cycles 2, 3, 4 in Chemotherapy Phase; Days 1, 15 and 29 of Cycles 1 and 2 in Maintenance/ Observation Phase and at End of Treatment(Baseline, first 3 months of Chemotherapy Phase (CP): Day 1 of Cycles 2, 3 and 4 (each cycle 21 days); Maintenance/Observation Phase (MP/OP): Days 1, 15 and 29 of Cycles 1 and 2 (each cycle 42 days) and at end of treatment (up to 27 months))
Number of Participants With Electrocardiogram (ECG) Abnormalities(Baseline to discontinuation from the study or death, whichever occurred first (maximum duration of 27 months))
Chemotherapy Phase: Area Under the Plasma Concentration Time Curve From Time Zero to Infinite Time (AUCinf) of Paclitaxel (QW Regimen)(Pre-dose and at 1, 3, 4, 5, 6, 10, and 24 hours post paclitaxel infusion on Day 1 of Cycle 2)
Duration of Response (DOR) as Assessed by Investigator(First response subsequently confirmed to progression of disease or start of new anti-cancer therapy or discontinuation from the study or death, whichever occurred first (maximum duration of 27 months))
Maintenance Progression-Free Survival (PFS) as Assessed by Investigator(From Day 1 of Cycle 1 (42 days) of maintenance phase to progression of disease or death, whichever occurred first (maximum duration of 27 months))
Percentage of Participants With Pathological Complete Response (pCR)(Baseline to progression of disease or discontinuation from the study or death, whichever occurred first (maximum duration of 27 months))
Duration of Response (DOR) as Assessed by Blinded Independent Central Review (BICR)(First response subsequently confirmed to progression of disease or start of new anti-cancer therapy or discontinuation from the study or death, whichever occurred first (maximum duration of 27 months))
Maintenance Progression-Free Survival as Assessed by Blinded Independent Central Review (BICR)(From Day 1 of Cycle 1 (42 days) of maintenance phase to progression of disease or death, whichever occurred first (maximum duration of 27 months))
Progression-Free Survival (PFS) as Assessed by Gynecological Cancer Intergroup (GCIG) Criteria(Baseline until disease progression by GCIG criteria or start of new anti-cancer therapy or discontinuation from the study or death, whichever occurred first (maximum duration of 27 months))
Number of Participants With Treatment-Emergent Adverse Events (AEs) Graded Based on, National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03(Baseline to discontinuation from the study or death, whichever occurred first (maximum duration of 36 months))
Number of Participants With Laboratory Abnormalities Greater Than or Equal to (>=) Grade 3, Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03(Baseline to discontinuation from the study or death, whichever occurred first (maximum duration of 27 months))
Chemotherapy Phase: Maximum Plasma Concentration (Cmax) of Paclitaxel (Once Every Three Weeks [Q3W] Regimen)(Pre-dose and at 1, 3, 4, 5, 6, 10, and 24 hours post paclitaxel infusion on Day 1 of Cycle 2)
Chemotherapy Phase: Maximum Plasma Concentration (Cmax) of Carboplatin (Total and Free)(Pre-dose and at 0.5, 1, 5, 6, 10, and 24 hours post carboplatin infusion on Day 1 of Cycle 2)
Chemotherapy Phase: Area Under the Concentration Time Curve From Time Zero to 24 Hours (AUC24) of Carboplatin (Total and Free)(Pre-dose (0 hour), 0.5, 1, 5, 6, 10, and 24 hours post carboplatin infusion on Day 1 of Cycle 2)
Functional Assessment of Ovarian Symptom Index- 18 (FOSI-18) Score(CP: Pre-dose on Day 1 of Cycles 2 to 6 (1 cycle= 21 days); MP/OP: Day 1 of Cycles 1 to 12 (1 cycle= 42 days), End of treatment (any time up to Month 27))
European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) Score(Baseline to discontinuation from the study or death, whichever occurred first (maximum duration of 36 months))
Chemotherapy Phase: Maximum Plasma Concentration (Cmax) of Paclitaxel (Once a Week [QW] Regimen)(Pre-dose and at 1, 3, 4, 5, 6, 10, and 24 hours post paclitaxel infusion on Day 1 of Cycle 2)
Chemotherapy Phase: Area Under the Plasma Concentration Time Curve From Time Zero to Infinite Time (AUCinf) of Paclitaxel (Q3W Regimen)(Pre-dose and at 1, 3, 4, 5, 6, 10, and 24 hours post paclitaxel infusion on Day 1 of Cycle 2)
Chemotherapy Phase: Area Under the Plasma Concentration Time Curve From Time Zero to Infinite Time (AUCinf) of Carboplatin (Total and Free)(Pre-dose and at 0.5, 1, 5, 6, 10, and 24 hours post carboplatin infusion on Day 1 of Cycle 2)
Chemotherapy Phase: Area Under the Concentration Time Curve From Time Zero to 24 Hours (AUC24) of Paclitaxel (QW Regimen)(Pre-dose (0 hour), 1, 3, 4, 5, 6, 10, and 24 hours post paclitaxel infusion on Day 1 of Cycle 2)
Chemotherapy Phase: Area Under the Concentration Time Curve From Time Zero to 24 Hours (AUC24) of Paclitaxel (Q3W Regimen)(Pre-dose (0 hour), 1, 3, 4, 5, 6, 10, and 24 hours post paclitaxel infusion on Day 1 of Cycle 2)
Maintenance Phase: Predose Plasma Concentration (Ctrough) of Avelumab(Pre-dose (0 hour) on Day 1 of Cycle 2)
Maintenance Phase: Maximum Plasma Concentration (Cmax) of Avelumab(End of avelumab infusion on Day 1 of Cycle 2)
Chemotherapy Phase: Maximum Plasma Concentration (Cmax) of Avelumab When Given With Paclitaxel and Carboplatin(End of infusion on Day 1 of Cycle 2)
Number of Participants With Positive Programmed Death Receptor-1 Ligand-1 (PD-L1) Biomarker Expression in Tumor Tissue as Assessed by Immunohistochemistry (IHC)(Up to 36 months)
Chemotherapy Phase: Predose Plasma Concentration (Ctrough) of Avelumab When Given With Paclitaxel and Carboplatin(Pre-dose (0 hour) on Day 1 of Cycle 2)
Number of Participants With Anti-Drug Antibodies (ADA) Against Avelumab by Never and Ever Positive Status(Up to 36 months)
Number of Participants With Neutralizing Antibodies (nAb) Against Avelumab by Never and Ever Positive Status(Up to 36 months)
Number of Participants With Positive Tumor-Infiltrating Cluster of Differentiation 8 (CD8+) T Lymphocytes Expression in Tumor Tissue as Assessed by Immunohistochemistry (IHC)(Up to 36 months)