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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03642132




Registration number
NCT03642132
Ethics application status
Date submitted
13/07/2018
Date registered
22/08/2018

Titles & IDs
Public title
Avelumab and Talazoparib in Untreated Advanced Ovarian Cancer (JAVELIN OVARIAN PARP 100)
Scientific 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)
Secondary ID [1] 0 0
2017-004456-30
Secondary ID [2] 0 0
B9991030
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Ovarian Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Ovarian and primary peritoneal

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Chemotherapy + avelumab followed by avelumab + talazoparib
Treatment: Drugs - Chemotherapy followed by talazoparib maintenance
Treatment: Drugs - Chemotherapy + bevacizumab followed by bevacizumab

Experimental: chemotherapy, avelumab and talazoparib - Platinum-based chemotherapy + avelumab followed by avelumab + talazoparib maintenance

Experimental: chemotherapy, and talazoparib - Platinum-based chemotherapy followed by talazoparib maintenance

Active comparator: chemotherapy and bevacizumab - Platinum-based chemotherapy + bevacizumab followed by bevacizumab maintenance


Treatment: Drugs: Chemotherapy + avelumab followed by avelumab + talazoparib
Chemotherapy Period Paclitaxel Carboplatin Avelumab

Maintenance Period Avelumab Talazoparib

Treatment: Drugs: Chemotherapy followed by talazoparib maintenance
Chemotherapy Period Paclitaxel Carboplatin

Maintenance Period Talazoparib

Treatment: Drugs: Chemotherapy + bevacizumab followed by bevacizumab
Chemotherapy Period Paclitaxel Carboplatin Bevacizumab

Maintenance Period Bevacizumab

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-free Survival (Participants With Newly Diagnosed Advanced Ovarian Cancer With Defects in DDR+)
Timepoint [1] 0 0
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 outcome [1] 0 0
Number of Participants With Treatment-Emergent Adverse Events (On-Treatment Period)
Timepoint [1] 0 0
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)
Secondary outcome [2] 0 0
Number of Participants With ADA Against Avelumab by Never and Ever Positive Status
Timepoint [2] 0 0
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.
Secondary outcome [3] 0 0
Pre-dose/Trough Concentration (Ctrough) for Avelumab (Chemotherapy Period)
Timepoint [3] 0 0
Day 1 of Cycles 1, 2, 3, and 4 in the chemotherapy period (1 cycle = 3 weeks)
Secondary outcome [4] 0 0
Pre-dose/Trough Concentration (Ctrough) for Avelumab (Maintenance Period)
Timepoint [4] 0 0
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.
Secondary outcome [5] 0 0
Cmax for Avelumab (Chemotherapy Period)
Timepoint [5] 0 0
Day 1 of Cycles 1, 2, 3, and 4 in the chemotherapy period (1 cycle = 3 weeks)
Secondary outcome [6] 0 0
Cmax for Avelumab (Maintenance Period)
Timepoint [6] 0 0
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.
Secondary outcome [7] 0 0
Ctrough for Talazoprib (Maintenance Period)
Timepoint [7] 0 0
Pre-dose on Days 1, 15 and 29 of Cycle 1
Secondary outcome [8] 0 0
Overall Survival (Participants of Both DDR+ and Unselected DDR Status)
Timepoint [8] 0 0
From 9 weeks up to approximately 3.5 years
Secondary outcome [9] 0 0
Progression-free Survival (Participants of Unselected DDR Status)
Timepoint [9] 0 0
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.
Secondary outcome [10] 0 0
Progression-free Survival (Participants of Both DDR+ and Unselected DDR Status)
Timepoint [10] 0 0
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.
Secondary outcome [11] 0 0
Progression-free Survival on Next-line Therapy. (Participants of Both DDR+ and Unselected DDR Status)
Timepoint [11] 0 0
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.
Secondary outcome [12] 0 0
PFS Per Gynecological Cancer Intergroup Criteria (Participants of Both DDR+ and Unselected DDR Status)
Timepoint [12] 0 0
From screening until death, end of study, or participant withdrawal of consent, whichever occurred first, up to approximately 3.5 years.
Secondary outcome [13] 0 0
Functional Assessment of Ovarian Symptom Index-18 (FOSI-18) Score
Timepoint [13] 0 0
3 years
Secondary outcome [14] 0 0
Programmed Death Receptor-1 Ligand-1 (PD-L1) Biomarker Expression in Tumor and Immune Cells as Assessed by Immunohistochemistry (IHC) at Baseline
Timepoint [14] 0 0
Baseline
Secondary outcome [15] 0 0
Number of Participants With Mutations in Key Oncogenes at Baseline
Timepoint [15] 0 0
Baseline
Secondary outcome [16] 0 0
EuroQol Group 5-Dimension 5-Level (EQ-5D-5L) Score
Timepoint [16] 0 0
3 years

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key 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-a), 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Epworth Foundation trading as Epworth HealthCare - East Melbourne
Recruitment hospital [2] 0 0
Epworth HealthCare, Clinical Trials & Research Centre - Richmond
Recruitment postcode(s) [1] 0 0
3002 - East Melbourne
Recruitment postcode(s) [2] 0 0
3121 - Richmond
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
New York
Country [5] 0 0
United States of America
State/province [5] 0 0
Ohio
Country [6] 0 0
United States of America
State/province [6] 0 0
Oregon
Country [7] 0 0
United States of America
State/province [7] 0 0
Tennessee
Country [8] 0 0
United States of America
State/province [8] 0 0
Texas
Country [9] 0 0
United States of America
State/province [9] 0 0
Virginia
Country [10] 0 0
United States of America
State/province [10] 0 0
Washington
Country [11] 0 0
Belgium
State/province [11] 0 0
Namur
Country [12] 0 0
Ireland
State/province [12] 0 0
Cork
Country [13] 0 0
Italy
State/province [13] 0 0
MI
Country [14] 0 0
Italy
State/province [14] 0 0
RM
Country [15] 0 0
Japan
State/province [15] 0 0
Niigata
Country [16] 0 0
Korea, Republic of
State/province [16] 0 0
Seoul
Country [17] 0 0
Russian Federation
State/province [17] 0 0
Moscow
Country [18] 0 0
Singapore
State/province [18] 0 0
Singapore
Country [19] 0 0
Taiwan
State/province [19] 0 0
Taipei

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Pfizer
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Pfizer CT.gov Call Center
Address 0 0
Pfizer
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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.
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.