Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    NCT03642132
Previous Study | Return to List | Next Study

Avelumab and Talazoparib in Untreated Advanced Ovarian Cancer (JAVELIN OVARIAN PARP 100)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03642132
Recruitment Status : Active, not recruiting
First Posted : August 22, 2018
Last Update Posted : February 21, 2021
Sponsor:
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE July 13, 2018
First Posted Date  ICMJE August 22, 2018
Last Update Posted Date February 21, 2021
Actual Study Start Date  ICMJE July 19, 2018
Estimated Primary Completion Date November 28, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 7, 2019)
Progression-Free Survival (PFS) - (Obsolete after effectiveness of protocol amendment 2) [ Time Frame: Baseline to measured progressive disease (up to approximately 41 months) ]
The original study objectives/endpoints are no longer applicable and/or feasible after effectiveness of protocol amendment 2. (Obsolete) The time from the date of randomization to the date of the first documentation of Progression of Disease or death due to any cause, whichever occurs first. Assessments to be completed by third-party blinded independent committee review.
Original Primary Outcome Measures  ICMJE
 (submitted: August 20, 2018)
Progression-Free Survival (PFS) [ Time Frame: Baseline to measured progressive disease (up to approximately 41 months) ]
The time from the date of randomization to the date of the first documentation of Progression of Disease or death due to any cause, whichever occurs first. Assessments to be completed by third-party blinded independent committee review.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 7, 2019)
  • Overall Survival (OS) - (Obsolete after effectiveness of protocol amendment 2) [ Time Frame: Baseline to date of death from any cause (up to approximately 93 months) ]
    The original study objectives/endpoints are no longer applicable and/or feasible after effectiveness of protocol amendment 2. (Obsolete) Overall survival (OS) is time from the date of randomization to the date of death due to any cause.
  • Euro Quality of Life (EQ-5D-5L) - (Obsolete after effectiveness of protocol amendment 2) [ Time Frame: Every 3 weeks during chemotherapy period (up to 18 weeks), and every 6 weeks (up to 24 months) during maintenance and follow-up period (up to 3 years). ]
    The original study objectives/endpoints are no longer applicable and/or feasible after effectiveness of protocol amendment 2. (Obsolete) Participant rated questionnaire to assess health related quality of life in terms of a single utility score. Health State Profile which has individualsrate their level of problems (none, slight, moderate, severe, or extreme/unable) in 5 areas (mobility, self care, usual activities, pain/discomfort, and anxiety/depression).
  • NFOSI-18 - (Obsolete after effectiveness of protocol amendment 2) [ Time Frame: Day 1, 8, 15 of cycles 1,2,3 and D1 of cycles 4, 5, 6 in chemotherpy period (cycle is 21 days) and every 6 weeks (up to 24 months) during maintenance and follow-up period (up to 3 years). ]
    The original study objectives/endpoints are no longer applicable and/or feasible after effectiveness of protocol amendment 2. (Obsolete) NFOSI-18 is an ovarian cancer-specific symptom index comprised of symptoms rated as highest priority by both oncology clinical experts and women with advanced ovarian cancer. DRS-P subscale include 9 physical symptoms/concerns (energy, pain, ill, stomach cramps, fatigue, constipation, stomach swelling, bowel control and sleep) and the disease related symptoms-emotional subscale include 1 emotional symptom/concern (worry condition will get worse). The treatment side effect subscale includes 5 items (nausea, hair loss, bothered by side effects, vomiting and skin problems). The functional well-being subscale includes 3 items (able to get around, enjoy life, and content with QoL).
  • ADA (Anti-Drug Antibodies) against Avelumab - (Obsolete) [ Time Frame: Every 3 weeks during 1st 4 cycles of chemotherapy ( cycle 21 days), day 1 and 29 during 1st cycle of maintenance (cycle 42 days) and every 12 weeks (up to 60 weeks). ]
    The original study objectives/endpoints are no longer applicable and/or feasible. (Obsolete) The percentage of participants with positive ADA and neutralizing antibodies will be summarized in treatment Arm A. All samples that are positive for ADA will also undergo characterization for Neutralizing Antibodies (NAb).
  • Progression Free Survival after the second line of therapy (PFS2) - (Obsolete after effectiveness of protocol amendment 2) [ Time Frame: Baseline up to second progression up to approximately 41 months. ]
    The original study objectives/endpoints are no longer applicable and/or feasible after effectiveness of protocol amendment 2. (Obsolete) Time from the date of randomization to the start of second subsequent treatment after first PD by Investigator assessment, or death from any cause, whichever occurs first.
  • Cmax - Talazoparib - (Obsolete after effectiveness of protocol amendment 2) [ Time Frame: Pre-dose on Days 1, 15, and 29 of Cycle 1 (Cycle is 42 days) of maintenance treatment. ]
    The original study objectives/endpoints are no longer applicable and/or feasible after effectiveness of protocol amendment 2. (Obsolete) Maximum Observed Plasma Concentration (Cmax)
  • Cmax - Avelumab - (Obsolete after effectiveness of protocol amendment 2) [ Time Frame: Every 3 weeks during 1st 4 cycles of chemotherapy ( cycle 21 days), day 1 and 29 during 1st cycle of maintenance (cycle 42 days) and every 12 weeks (up to 60 weeks). ]
    The original study objectives/endpoints are no longer applicable and/or feasible after effectiveness of protocol amendment 2. (Obsolete) Maximum Observed Plasma Concentration (Cmax).
Original Secondary Outcome Measures  ICMJE
 (submitted: August 20, 2018)
  • Overall Survival (OS) [ Time Frame: Baseline to date of death from any cause (up to approximately 93 months) ]
    Overall survival (OS) is time from the date of randomization to the date of death due to any cause.
  • Euro Quality of Life (EQ-5D-5L) [ Time Frame: Every 3 weeks during chemotherapy period (up to 18 weeks), and every 6 weeks (up to 24 months) during maintenance and follow-up period (up to 3 years). ]
    Participant rated questionnaire to assess health related quality of life in terms of a single utility score. Health State Profile which has individualsrate their level of problems (none, slight, moderate, severe, or extreme/unable) in 5 areas (mobility, self care, usual activities, pain/discomfort, and anxiety/depression).
  • NFOSI-18 [ Time Frame: Day 1, 8, 15 of cycles 1,2,3 and D1 of cycles 4, 5, 6 in chemotherpy period (cycle is 21 days) and every 6 weeks (up to 24 months) during maintenance and follow-up period (up to 3 years). ]
    NFOSI-18 is an ovarian cancer-specific symptom index comprised of symptoms rated as highest priority by both oncology clinical experts and women with advanced ovarian cancer. DRS-P subscale include 9 physical symptoms/concerns (energy, pain, ill, stomach cramps, fatigue, constipation, stomach swelling, bowel control and sleep) and the disease related symptoms-emotional subscale include 1 emotional symptom/concern (worry condition will get worse). The treatment side effect subscale includes 5 items (nausea, hair loss, bothered by side effects, vomiting and skin problems). The functional well-being subscale includes 3 items (able to get around, enjoy life, and content with QoL).
  • ADA (Anti-Drug Antibodies) against Avelumab [ Time Frame: Every 3 weeks during 1st 4 cycles of chemotherapy ( cycle 21 days), day 1 and 29 during 1st cycle of maintenance (cycle 42 days) and every 12 weeks (up to 60 weeks). ]
    The percentage of participants with positive ADA and neutralizing antibodies will be summarized in treatment Arm A. All samples that are positive for ADA will also undergo characterization for Neutralizing Antibodies (NAb).
  • Progression Free Survival after the second line of therapy (PFS2) [ Time Frame: Baseline up to second progression up to approximately 41 months. ]
    Time from the date of randomization to the start of second subsequent treatment after first PD by Investigator assessment, or death from any cause, whichever occurs first.
  • Cmax - Talazoparib [ Time Frame: Pre-dose on Days 1, 15, and 29 of Cycle 1 (Cycle is 42 days) of maintenance treatment. ]
    Maximum Observed Plasma Concentration (Cmax)
  • Cmax - Avelumab [ Time Frame: Every 3 weeks during 1st 4 cycles of chemotherapy ( cycle 21 days), day 1 and 29 during 1st cycle of maintenance (cycle 42 days) and every 12 weeks (up to 60 weeks). ]
    Maximum Observed Plasma Concentration (Cmax).
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Avelumab and Talazoparib in Untreated Advanced Ovarian Cancer (JAVELIN OVARIAN PARP 100)
Official Title  ICMJE A RANDOMIZED, OPEN-LABEL, MULTICENTER, PHASE 3 STUDY TO EVALUATE THE EFFICACY AND SAFETY OF AVELUMAB IN COMBINATION WITH CHEMOTHERAPY FOLLOWED BY MAINTENANCE THERAPY OF AVELUMAB IN COMBINATION WITH THE POLY (ADENOSINE DIPHOSPHATE [ADP]-RIBOSE) POLYMERASE (PARP) INHIBITOR TALAZOPARIB IN PATIENTS WITH PREVIOUSLY UNTREATED ADVANCED OVARIAN CANCER (JAVELIN OVARIAN PARP100)
Brief Summary JAVELIN Ovarian PARP 100 (B9991030) is an open-label, randomized study designed to evaluate the efficacy and safety of avelumab in combination with chemotherapy followed by maintenance therapy of avelumab in combination with talazoparib versus an active comparator in treatment-naïve patients with locally advanced or metastatic ovarian cancer (Stage III or Stage IV). On March 19, 2019, Sponsors alliance announced the discontinuation of the ongoing Phase III study, and the decision was based on several factors, including previous announced interim results from JAVELIN Ovarian 100 study (B9991010). Patients who remain in B9991030 study will continue receiving their randomized treatment assigned and will be monitored for appropriate safety assessments until treatment discontinuation.
Detailed Description

JAVELIN Ovarian PARP 100 (B9991030) is an open-label, international, multi-center, randomized study designed to evaluate the efficacy and safety of avelumab in combination with chemotherapy followed by maintenance therapy of avelumab in combination with talazoparib versus an active comparator in treatment-naïve patients with locally advanced or metastatic ovarian cancer (Stage III or Stage IV). The primary endpoint is progression-free survival (PFS) as determined based on blinded independent central review (BICR) assessment per RECIST v1.1.

On March 19, 2019, Sponsors alliance announced the discontinuation of the ongoing Phase III JAVELIN Ovarian PARP 100 study. The alliance has notified health authorities and trial investigators of the decision to discontinue the trial. The decision was based on several emerging factors since the trial's initiation, including the previously announced interim results from JAVELIN Ovarian 100 study (B9991010), which was stopped due to futility of efficacy at a planned interim analysis on 21 December 2018. The alliance determined that the degree of benefit observed with avelumab in frontline ovarian cancer in that study does not support continuation of the JAVELIN Ovarian PARP 100 trial in an unselected patient population and emphasizes the need to better understand the role of immunotherapy in ovarian cancer. Additional factors include the rapidly changing treatment landscape and the approval of a PARP inhibitor in the frontline maintenance setting. The decision to discontinue the JAVELIN Ovarian PARP 100 trial was not made for safety reasons.

Patients who remain in the study will continue receiving investigational products according to their randomized treatment assignment and will be monitored for appropriate safety assessments until treatment discontinuation.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Ovarian Cancer
Intervention  ICMJE
  • Drug: Chemotherapy + avelumab followed by avelumab + talazoparib

    Chemotherapy Period Paclitaxel Carboplatin Avelumab

    Maintenance Period Avelumab Talazoparib

  • Drug: Chemotherapy followed by talazoparib maintenance

    Chemotherapy Period Paclitaxel Carboplatin

    Maintenance Period Talazoparib

  • Drug: Chemotherapy + bevacizumab followed by bevacizumab

    Chemotherapy Period Paclitaxel Carboplatin Bevacizumab

    Maintenance Period Bevacizumab

Study Arms  ICMJE
  • Experimental: chemotherapy, avelumab and talazoparib
    Platinum-based chemotherapy + avelumab followed by avelumab + talazoparib maintenance
    Intervention: Drug: Chemotherapy + avelumab followed by avelumab + talazoparib
  • Experimental: chemotherapy, and talazoparib
    Platinum-based chemotherapy followed by talazoparib maintenance
    Intervention: Drug: Chemotherapy followed by talazoparib maintenance
  • Active Comparator: chemotherapy and bevacizumab
    Platinum-based chemotherapy + bevacizumab followed by bevacizumab maintenance
    Intervention: Drug: Chemotherapy + bevacizumab followed by bevacizumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: August 13, 2019)
79
Original Estimated Enrollment  ICMJE
 (submitted: August 20, 2018)
720
Estimated Study Completion Date  ICMJE November 28, 2021
Estimated Primary Completion Date November 28, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologically confirmed Stage III IV epithelial ovarian, fallopian tube, or primary peritoneal cancer including carcinosarcoma with high-grade serous component.
  • Patients must be candidates for bevacizumab in combination with platinum based chemotherapy and previously untreated.
  • Must have completed a primary surgical debulking procedure, or be candidates for neoadjuvant chemotherapy with planned interval debulking surgery.

    1. Patients who completed primary debulking must have had incompletely resected disease that is macroscopically/grossly visible and at least with lesions >1 mm and be randomized at a maximum of 8 weeks after surgery.
    2. For patients who are candidates for neoadjuvant chemotherapy, the diagnoses must have been confirmed by:

      • Core tissue (not fine-needle aspiration) biopsy is required for diagnosis.
      • Stage IIIC-IV documented via imaging or surgery (without attempt at cytoreduction).
      • Serum CA-125/CEA ratio >25. If the serum CA-125/CEA ratio is <25, then workup should be negative for the presence of a primary gastrointestinal or breast malignancy (<6 weeks before start of neoadjuvant treatment).
      • Randomization must occur within 8 weeks after diagnosis.
  • Availability of an archival FFPE tumor tissue block or a minimum of 25 slides, together with an accompanying original H&E slide. If archived FFPE tissue is not available, a de novo (ie, fresh) tumor sample must be obtained in accordance with local institutional practice for tumor biopsies. Tumor tissue must contain 40% or greater tumor nuclei per central laboratory assessment.
  • ECOG performance status 0-1
  • Age >=18 years (or >=20 years in Japan).
  • Adequate bone marrow, hepatic, and renal function and blood coagulation

Exclusion Criteria:

  • Non-epithelial tumors or ovarian tumors with low malignant potential (ie, borderline tumors) or mucinous tumors.
  • Patients for whom intraperitoneal cytotoxic chemotherapy is planned.
  • Prior exposure to immunotherapy with interleukin (IL)-2, interferon alpha (IFN-α), or an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte associated antigen 4 (anti-CTLA4) antibody (including ipilimumab), or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways, excluding therapeutic anticancer vaccines.
  • Prior treatment with a PARP inhibitor.
  • Prior treatment with any anti-vascular endothelial growth factor (VEGF) drug, including bevacizumab.
  • Major surgery (other than debulking or exploratory surgery for ovarian cancer) for any reason within 4 weeks prior to randomization and/or incomplete recovery from surgery.
  • Prior radiotherapy to any portion of the abdominal cavity or pelvis. Prior radiation for localized cancer of the breast, head and neck, or skin is permitted, provided that it was completed more than three years prior to registration, and the patient remains free of recurrent or metastatic disease.
  • Prior targeted therapy (including but not limited to vaccines, antibodies, tyrosine kinase inhibitors) or hormonal therapy for management of their ovarian, peritoneal primary or fallopian tube carcinoma.
  • Prior organ transplantation including allogenic stem cell transplantation.
  • Diagnosis of Myelodysplastic Syndrome (MDS).
  • Known symptomatic brain metastases requiring steroids. Patients with previously diagnosed brain metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to study enrollment, have discontinued corticosteroid treatment for these metastases for at least 4 weeks and are neurologically stable.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Gender Based Eligibility: Yes
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Belgium,   Ireland,   Italy,   Japan,   Korea, Republic of,   Russian Federation,   Singapore,   Taiwan,   United States
Removed Location Countries Croatia,   Estonia,   Hungary,   Poland,   Slovakia,   Ukraine
 
Administrative Information
NCT Number  ICMJE NCT03642132
Other Study ID Numbers  ICMJE B9991030
2017-004456-30 ( EudraCT Number )
B9991030 ( Other Identifier: Alias Study Number )
JAVELIN OVARIAN PARP 100 ( Other Identifier: Alias Study Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Bradley Monk, MD Department of Obstetrics and Gynecology, University of Arizona College of Medicine - Phoenix
Study Chair: Jonathan Ledermann, MD UCL Cancer Institute at University College London
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date February 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP