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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT03642132
Ethics application status
Date submitted
13/07/2018
Date registered
22/08/2018
Date last updated
20/08/2019

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 (PFS) - (Obsolete after effectiveness of protocol amendment 2) - 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.
Timepoint [1] 0 0
Baseline to measured progressive disease (up to approximately 41 months)
Secondary outcome [1] 0 0
Overall Survival (OS) - (Obsolete after effectiveness of protocol amendment 2) - 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.
Timepoint [1] 0 0
Baseline to date of death from any cause (up to approximately 93 months)
Secondary outcome [2] 0 0
Euro Quality of Life (EQ-5D-5L) - (Obsolete after effectiveness of protocol amendment 2) - 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).
Timepoint [2] 0 0
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).
Secondary outcome [3] 0 0
NFOSI-18 - (Obsolete after effectiveness of protocol amendment 2) - 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).
Timepoint [3] 0 0
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).
Secondary outcome [4] 0 0
ADA (Anti-Drug Antibodies) against Avelumab - (Obsolete) - 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).
Timepoint [4] 0 0
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).
Secondary outcome [5] 0 0
Progression Free Survival after the second line of therapy (PFS2) - (Obsolete after effectiveness of protocol amendment 2) - 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.
Timepoint [5] 0 0
Baseline up to second progression up to approximately 41 months.
Secondary outcome [6] 0 0
Cmax - Talazoparib - (Obsolete after effectiveness of protocol amendment 2) - The original study objectives/endpoints are no longer applicable and/or feasible after effectiveness of protocol amendment 2.
(Obsolete) Maximum Observed Plasma Concentration (Cmax)
Timepoint [6] 0 0
Pre-dose on Days 1, 15, and 29 of Cycle 1 (Cycle is 42 days) of maintenance treatment.
Secondary outcome [7] 0 0
Cmax - Avelumab - (Obsolete after effectiveness of protocol amendment 2) - The original study objectives/endpoints are no longer applicable and/or feasible after effectiveness of protocol amendment 2.
(Obsolete) Maximum Observed Plasma Concentration (Cmax).
Timepoint [7] 0 0
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).

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
Gender
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
Active, not recruiting
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 hospital [3] 0 0
Slade Compounding - Slade Pharmaceuticals - 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
Poland
State/province [17] 0 0
Grudziadz
Country [18] 0 0
Russian Federation
State/province [18] 0 0
Moscow
Country [19] 0 0
Singapore
State/province [19] 0 0
Singapore
Country [20] 0 0
Taiwan
State/province [20] 0 0
New Taipei city
Country [21] 0 0
Taiwan
State/province [21] 0 0
New Taipei City
Country [22] 0 0
Taiwan
State/province [22] 0 0
Taipei

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

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT03642132
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Bradley Monk, MD
Address 0 0
Department of Obstetrics and Gynecology, University of Arizona College of Medicine - Phoenix
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

Summary results
Other publications