Clinical trial NCT03642132: Avelumab and Talazoparib in Untreated Advanced Ovarian Cancer (JAVELIN OVARIAN PARP 100)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Ovarian Cancer
Keywords: untreated epithelial ovarian cancer
fallopian tube cancer
primary peritoneal cancer
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2018-08-22
Enrollment: 79
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Progression-free Survival (Participants With Newly Diagnosed Advanced Ovarian Cancer With Defects in DDR+）
timeFrame: At screening, 9 and 18 weeks after date of randomization, then every 12 weeks thereafter until PD by Blinded Independent Central Review (BICR) regardless of initiation of new anti-cancer therapy
Secondary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (On-Treatment Period)
timeFrame: From the first dose of study treatment through up to 30 days after minimum last dose of study treatment or start day of new anti-cancer drug therapy minus 1 day (maximum up to 3.5 years approximately)
measure: Number of Participants With ADA Against Avelumab by Never and Ever Positive Status
timeFrame: Day 1 pre-dose of Cycles 1, 2, 3, and 4 in the chemotherapy period and Days 1 and 29 of Cycle 1 and Day 1 of Cycles 2, 4, 6, and 10 in the maintenance period and at the end of treatment/withdrawal, up to 27 months.
measure: Pre-dose/Trough Concentration (Ctrough) for Avelumab (Chemotherapy Period)
timeFrame: Day 1 of Cycles 1, 2, 3, and 4 in the chemotherapy period (1 cycle = 3 weeks)
measure: Pre-dose/Trough Concentration (Ctrough) for Avelumab (Maintenance Period)
timeFrame: Pre-dose on Days 1 and 29 of Cycle 1 and Day 1 of Cycles 2, 4, 6, and 10 in the maintenance period (1 cycle = 6 weeks) and at the end of treatment, up to 27 months.
measure: Cmax for Avelumab (Chemotherapy Period)
timeFrame: Day 1 of Cycles 1, 2, 3, and 4 in the chemotherapy period (1 cycle = 3 weeks)
measure: Cmax for Avelumab (Maintenance Period)
timeFrame: Day 1 pre-dose of Cycles 1, 2, 3, and 4 in the chemotherapy period and Days 1 and 29 of Cycle 1 and Day 1 of Cycles 2, 4, 6, and 10 in the maintenance period and at the end of treatment/withdrawal, up to 27 months.
measure: Ctrough for Talazoprib (Maintenance Period)
timeFrame: Pre-dose on Days 1, 15 and 29 of Cycle 1
measure: Overall Survival (Participants of Both DDR+ and Unselected DDR Status)
timeFrame: From 9 weeks up to approximately 3.5 years
measure: Progression-free Survival (Participants of Unselected DDR Status)
timeFrame: At screening, 9 and 18 weeks after date of randomization, then every 12 weeks thereafter until PD by BICR regardless of initiation of new anti-cancer therapy, up to approximately 3.5 years.
measure: Progression-free Survival (Participants of Both DDR+ and Unselected DDR Status)
timeFrame: At screening, 9 and 18 weeks after date of randomization, then every 12 weeks thereafter until PD by BICR regardless of initiation of new anti-cancer therapy, up to approximately 3.5 years.
measure: Progression-free Survival on Next-line Therapy. (Participants of Both DDR+ and Unselected DDR Status)
timeFrame: From screening until the participant had objective PD on or prior to start of next-line anti-cancer treatment, and started a second subsequent anti-cancer treatment or the participant died, up to approximately 3.5 years.
measure: PFS Per Gynecological Cancer Intergroup Criteria (Participants of Both DDR+ and Unselected DDR Status)
timeFrame: From screening until death, end of study, or participant withdrawal of consent, whichever occurred first, up to approximately 3.5 years.
measure: Functional Assessment of Ovarian Symptom Index-18 (FOSI-18) Score
timeFrame: 3 years
measure: Programmed Death Receptor-1 Ligand-1 (PD-L1) Biomarker Expression in Tumor and Immune Cells as Assessed by Immunohistochemistry (IHC) at Baseline
timeFrame: Baseline
measure: Number of Participants With Mutations in Key Oncogenes at Baseline
timeFrame: Baseline
measure: EuroQol Group 5-Dimension 5-Level (EQ-5D-5L) Score
timeFrame: 3 years
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Arizona Oncology Associates, PC - HAL
state: Arizona
city: Phoenix
country: United States
facility: Arizona Oncology Associates, PC - HAL
state: Arizona
city: Scottsdale
country: United States
facility: Arizona Oncology Associates, PC - HAL
state: Arizona
city: Tempe
country: United States
facility: Arizona Oncology Associates, PC - HAL
state: Arizona
city: Tucson
country: United States
facility: Arizona Oncology Associates, PC - HOPE
state: Arizona
city: Tucson
country: United States
facility: Arizona Oncology Associates, PC - HOPE
state: Arizona
city: Santa Barbara
country: United States
facility: Sansum Clinic
state: California
city: Solvang
country: United States
facility: Sansum Clinic
state: California
city: New Haven
country: United States
facility: Smilow Cancer Hospital at Yale-New Haven
state: Connecticut
city: Bronx
country: United States
facility: Montefiore Medical Center - EPC
state: New York
city: Bronx
country: United States
facility: Montefiore Medical Center, Department of Obstetrics and Gynecology and Women's Health
state: New York
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Bronx
country: United States
facility: Montefiore Medical Center-Centennial Facility
state: New York
city: Mineola
country: United States
facility: NYU Winthrop Hospital, Gynecologic Oncology
state: New York
city: Mineola
country: United States
facility: NYU Winthrop Hospital, Infusion Center
state: New York
city: Mineola
country: United States
facility: NYU Winthrop Radiology
state: New York
city: Cincinnati
country: United States
facility: Oncology Hematology Care, Inc.
state: Ohio
city: Cincinnati
country: United States
facility: Oncology Hematology Care Inc
state: Ohio
city: Cincinnati
country: United States
facility: Oncology Hematology Care Inc
state: Ohio
city: Cincinnati
country: United States
facility: Oncology Hematology Care, Inc.
state: Ohio
city: Portland
country: United States
facility: Northwest Cancer Specialists, P.C.
state: Oregon
city: Portland
country: United States
facility: Northwest Cancer Specialists, P.C.
state: Oregon
city: Portland
country: United States
facility: Northwest Cancer Specialists, P.C.
state: Oregon
city: Tualatin
country: United States
facility: Northwest Cancer Specialists, P.C.
state: Oregon
city: Dickson
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Franklin
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Gallatin
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Hermitage
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Lebanon
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Murfreesboro
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Nashville
country: United States
facility: The Sarah Cannon Research Institute
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Shelbyville
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Smyrna
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Bedford
country: United States
facility: Texas Oncology Bedford
state: Texas
city: Fort Worth
country: United States
facility: Texas Oncology
state: Texas
city: Irving
country: United States
facility: US Oncology Investigational Products Center (IPC)
state: Texas
city: Irving
country: United States
facility: US Oncology Investigational Products Center
state: Texas
city: San Antonio
country: United States
facility: Texas Oncology- San Antonio
state: Texas
city: Chesapeake
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Norfolk
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Virginia Beach
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Vancouver
country: United States
facility: Northwest Cancer Specialists, P.C.
state: Washington
city: East Melbourne
country: Australia
facility: Epworth Foundation trading as Epworth HealthCare
state: Victoria
city: Richmond
country: Australia
facility: Epworth HealthCare, Clinical Trials & Research Centre
state: Victoria
city: Namur
country: Belgium
facility: CHU-UCL Namur/Site Sainte Elisabeth
city: Cork
country: Ireland
facility: Bon Secours Hospital
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia (IEO)
state: MI
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario A. Gemelli IRCCS
state: RM
city: Niigata
country: Japan
facility: Niigata Cancer Center Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Gangnam Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Gangnam Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Clinical Trial Pharmacy, Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Moscow
country: Russian Federation
facility: Limited Liability Company "VitaMed" (LLC "VitaMed")
city: Singapore
country: Singapore
facility: Department of Nuclear Medicine and Molecular Imaging
city: Singapore
country: Singapore
facility: SingHealth Investigational Medicine Unit
city: Singapore
country: Singapore
facility: National Cancer Centre Singapore
city: Singapore
country: Singapore
facility: Department of Pathology
city: Singapore
country: Singapore
facility: Raffles Hospital
city: Singapore
country: Singapore
facility: Raffles Radiology
city: Singapore
country: Singapore
facility: Farrer Park Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taipei
country: Taiwan
facility: Department of Radiology, Koo Foundation Sun Yat-Sen Cancer Center
city: Taipei
country: Taiwan
facility: Division of Pharmacy, Koo Foundation Sun Yat-Sen Cancer Center
city: Taipei
country: Taiwan
facility: Koo Foundation Sun Yat-Sen Cancer Center
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: