Ovarian CancerPhase 3NCT03642132
Avelumab and Talazoparib in Untreated Advanced Ovarian Cancer (JAVELIN OVARIAN PARP 100)
A Phase 3 study testing Chemotherapy + avelumab followed by avelumab + talazoparib, Chemotherapy followed by talazoparib maintenance and Chemotherapy + bevacizumab followed by bevacizumab in people with Ovarian Cancer, run by Pfizer at 72 sites in 10 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Ovarian Cancer
- What is being tested?
- Chemotherapy + avelumab followed by avelumab + talazoparib, Chemotherapy followed by talazoparib maintenance and Chemotherapy + bevacizumab followed by bevacizumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 79 participants
- Where
- 72 sitesin 10 countries
- Study dates
- 19 Jul 2018to 22 Dec 2021
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
- 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.
- 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.
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- 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
Who cannot join
- 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.
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- 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.
Trial locations and contacts
72 sites in 10 countries.
72 sites in 10 countries
United States46 sites
Texas Oncology Bedford
Bedford, Texas, 76022
Virginia Oncology Associates
Chesapeake, Virginia, 23320
Oncology Hematology Care, Inc.
Cincinnati, Ohio, 45211
Oncology Hematology Care Inc
Cincinnati, Ohio, 45230
Oncology Hematology Care Inc
Cincinnati, Ohio, 45236
Oncology Hematology Care, Inc.
Cincinnati, Ohio, 45242
Tennessee Oncology, PLLC
Dickson, Tennessee, 37055
Texas Oncology
Fort Worth, Texas, 76104
Tennessee Oncology, PLLC
Franklin, Tennessee, 37067
Tennessee Oncology, PLLC
Gallatin, Tennessee, 37066
Tennessee Oncology, PLLC
Hermitage, Tennessee, 37076
US Oncology Investigational Products Center (IPC)
Irving, Texas, 75063
US Oncology Investigational Products Center
Irving, Texas, 75063
Tennessee Oncology, PLLC
Lebanon, Tennessee, 37090
NYU Winthrop Hospital, Gynecologic Oncology
Mineola, New York, 11501
NYU Winthrop Hospital, Infusion Center
Mineola, New York, 11501
NYU Winthrop Radiology
Mineola, New York, 11501
Tennessee Oncology, PLLC
Murfreesboro, Tennessee, 37129
Tennessee Oncology, PLLC
Nashville, Tennessee, 37203
The Sarah Cannon Research Institute
Nashville, Tennessee, 37203
Tennessee Oncology, PLLC
Nashville, Tennessee, 37205
Tennessee Oncology, PLLC
Nashville, Tennessee, 37207
Tennessee Oncology, PLLC
Nashville, Tennessee, 37211
Smilow Cancer Hospital at Yale-New Haven
New Haven, Connecticut, 06510
Virginia Oncology Associates
Norfolk, Virginia, 23502
Arizona Oncology Associates, PC - HAL
Phoenix, Arizona, 85016
Arizona Oncology Associates, PC - HAL
Phoenix, Arizona, 85027
Northwest Cancer Specialists, P.C.
Portland, Oregon, 97213-2982
Northwest Cancer Specialists, P.C.
Portland, Oregon, 97225
Northwest Cancer Specialists, P.C.
Portland, Oregon, 97227
Texas Oncology- San Antonio
San Antonio, Texas, 78240
Sansum Clinic
Santa Barbara, California, 93105
Arizona Oncology Associates, PC - HAL
Scottsdale, Arizona, 85258
Tennessee Oncology, PLLC
Shelbyville, Tennessee, 37160
Tennessee Oncology, PLLC
Smyrna, Tennessee, 37167
Sansum Clinic
Solvang, California, 93463
Arizona Oncology Associates, PC - HAL
Tempe, Arizona, 85284
Montefiore Medical Center - EPC
The Bronx, New York, 10461
Montefiore Medical Center, Department of Obstetrics and Gynecology and Women's Health
The Bronx, New York, 10461
Montefiore Medical Center
The Bronx, New York, 10461
Montefiore Medical Center-Centennial Facility
The Bronx, New York, 10467
Northwest Cancer Specialists, P.C.
Tualatin, Oregon, 97062
Arizona Oncology Associates, PC - HOPE
Tucson, Arizona, 85704
Arizona Oncology Associates, PC - HOPE
Tucson, Arizona, 85711
Northwest Cancer Specialists, P.C.
Vancouver, Washington, 98684
Virginia Oncology Associates
Virginia Beach, Virginia, 23456
Singapore7 sites
Department of Nuclear Medicine and Molecular Imaging
Singapore, 169608
SingHealth Investigational Medicine Unit
Singapore, 169608
National Cancer Centre Singapore
Singapore, 169610
Department of Pathology
Singapore, 169856
Raffles Hospital
Singapore, 188770
Raffles Radiology
Singapore, 188770
Farrer Park Hospital
Singapore, 217562
South Korea7 sites
Korea University Anam Hospital
Seoul, 02841
Severance Hospital, Yonsei University Health System
Seoul, 03722
Asan Medical Center
Seoul, 05505
Gangnam Severance Hospital
Seoul, 06229
Gangnam Severance Hospital
Seoul, 06273
Clinical Trial Pharmacy, Samsung Medical Center
Seoul, 06351
Samsung Medical Center
Seoul, 06351
Taiwan4 sites
Taipei Veterans General Hospital
Taipei, 11217
Department of Radiology, Koo Foundation Sun Yat-Sen Cancer Center
Taipei, 112
Division of Pharmacy, Koo Foundation Sun Yat-Sen Cancer Center
Taipei, 112
Koo Foundation Sun Yat-Sen Cancer Center
Taipei, 112
Australia2 sites
Epworth Foundation trading as Epworth HealthCare
East Melbourne, Victoria, 3002
Epworth HealthCare, Clinical Trials & Research Centre
Richmond, Victoria, 3121
Italy2 sites
Istituto Europeo di Oncologia (IEO)
Milan, MI, 20141
Fondazione Policlinico Universitario A. Gemelli IRCCS
Roma, RM, 00168
Russia1 site
Limited Liability Company "VitaMed" (LLC "VitaMed")
Moscow, 121309
About this study
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)
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.
Read the 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.
- Conditions
- Ovarian Cancer
- Being tested
- Chemotherapy + avelumab followed by avelumab + talazoparib, Chemotherapy followed by talazoparib maintenance, Chemotherapy + bevacizumab followed by bevacizumab
- Keywords
- untreated epithelial ovarian cancer, fallopian tube cancer, primary peritoneal cancer
- Medical subject headings
- Ovarian Neoplasms, Fallopian Tube Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Chemotherapy + avelumab followed by avelumab + talazoparibDrug
Chemotherapy Period Paclitaxel Carboplatin Avelumab
Maintenance Period Avelumab Talazoparib
Chemotherapy followed by talazoparib maintenanceDrug
Chemotherapy Period Paclitaxel Carboplatin
Maintenance Period Talazoparib
Chemotherapy + bevacizumab followed by bevacizumabDrug
Chemotherapy Period Paclitaxel Carboplatin Bevacizumab
Maintenance Period Bevacizumab
| Study group | Role | What they receive |
|---|---|---|
| chemotherapy, avelumab and talazoparib | Experimental | Platinum-based chemotherapy + avelumab followed by avelumab + talazoparib maintenance Receives: Drug: Chemotherapy + avelumab followed by avelumab + talazoparib |
| chemotherapy, and talazoparib | Experimental | Platinum-based chemotherapy followed by talazoparib maintenance Receives: Drug: Chemotherapy followed by talazoparib maintenance |
| chemotherapy and bevacizumab | Active comparator | Platinum-based chemotherapy + bevacizumab followed by bevacizumab maintenance Receives: Drug: Chemotherapy + bevacizumab followed by bevacizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free Survival (Participants With Newly Diagnosed Advanced Ovarian Cancer With Defects in DDR+）
Progression-free survival (PFS) was defined as the time from randomization to the date of the first documentation of objective progressive disease (PD) or death due to any cause, whichever occurred first. PD: >=20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to relative increase of 20%, sum must also demonstrate an absolute increase of at least 5mm, appearance of one or more new lesions was considered PD.
Measured: 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 (16)
Number of Participants With Treatment-Emergent Adverse Events (On-Treatment Period)
An adverse event (AE) was any untoward medical occurrence in a study participant administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. A serious adverse event (SAE) was any untoward medical occurrence at any dose that resulted in death, was lifethreatening (immediate risk of death), required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions), resulted in congenital anomaly/birth defect or considered to be an important medical event. AEs included SAEs and non-serious AEs.
On-treatment period was defined as the time 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.
Measured: 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)
Number of Participants With ADA Against Avelumab by Never and Ever Positive Status
Predose Anti-drug antibodies (ADA) samples were collected within 2 hours prior to avelumab dosing and drawn from the contralateral arm of the avelumab infusion.
Measured: 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.
Pre-dose/Trough Concentration (Ctrough) for Avelumab (Chemotherapy Period)
Ctrough was defined as predose concentration during multiple dosing and it was observed directly from data
Measured: Day 1 of Cycles 1, 2, 3, and 4 in the chemotherapy period (1 cycle = 3 weeks)
Pre-dose/Trough Concentration (Ctrough) for Avelumab (Maintenance Period)
Ctrough was defined as predose concentration during multiple dosing and it was observed directly from data
Measured: 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.
Cmax for Avelumab (Chemotherapy Period)
Cmax was defined as maximum observed plasma concentration and it was observed directly from data
Measured: Day 1 of Cycles 1, 2, 3, and 4 in the chemotherapy period (1 cycle = 3 weeks)
Cmax for Avelumab (Maintenance Period)
Cmax was defined as maximum observed plasma concentration and it was observed directly from data
Measured: 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.
Ctrough for Talazoprib (Maintenance Period)
Ctrough was defined as predose concentration during multiple dosing and it was observed directly from data.
Measured: Pre-dose on Days 1, 15 and 29 of Cycle 1
Overall Survival (Participants of Both DDR+ and Unselected DDR Status)
OS was defined as the time from the date of randomization to the date of death due to any cause.
Measured: From 9 weeks up to approximately 3.5 years
Progression-free Survival (Participants of Unselected DDR Status)
PFS was defined as the time from the date of randomization to the date of the first documentation of PD or death due to any cause, whichever occured first.
Measured: 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.
Progression-free Survival (Participants of Both DDR+ and Unselected DDR Status)
PFS was defined as the time from randomization to the date of the first documentation of objective progressive disease(PD) or death due to any cause, whichever occured first. Participants was defined as having defective DDR (DDR+) or having intact DDR (DDR ) using a next generation sequencing based assay method.
Measured: 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.
Progression-free Survival on Next-line Therapy. (Participants of Both DDR+ and Unselected DDR Status)
Progression-free survival on next-line therapy (PFS2) was defined as time from the date of randomization to the start of second subsequent treatment after first documentation of PD, or death from any cause, whichever occured first. Participants was defined as having defective DDR (DDR+) or having intact DDR (DDR ) using a next generation sequencing based assay method
Measured: 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.
PFS Per Gynecological Cancer Intergroup Criteria (Participants of Both DDR+ and Unselected DDR Status)
PFS based on investigator assessment per Gynecological Cancer Intergroup criteria (GCIG) would be assessed incorporating both Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and CA 125. Participants was defined as having defective DDR (DDR+) or having intact DDR (DDR ) using a next generation sequencing based assay method.
Measured: From screening until death, end of study, or participant withdrawal of consent, whichever occurred first, up to approximately 3.5 years.
Functional Assessment of Ovarian Symptom Index-18 (FOSI-18) Score
NFOSI-18 was an ovarian cancer-specific symptom index comprised of symptoms rated as highest priority by both oncology clinical experts and women with advanced ovarian cancer. It was specifically designed to be a stand-alone instrument to measure disease-related symptoms, treatment side effects and function/well-being in participants with ovarian cancer.
The NFOSI-18 has several subscales: disease-related symptoms physical subscale(9 items), disease-related symptoms emotional subscale(1 item), treatment-related side effect subscale (5 items) and functional well-being (3 items). A high score was good. A score of "0" was a severely symptomatic participant and the highest possible score was an asymptomatic participant.
Measured: 3 years
Programmed Death Receptor-1 Ligand-1 (PD-L1) Biomarker Expression in Tumor and Immune Cells as Assessed by Immunohistochemistry (IHC) at Baseline
The number of PD-L1 positive cells and/or qualitative assessment of PD-L1 staining on tumor and inflammatory cells in regions of interest that were defined by tumor cell morphology and the presence or absence of inflammatory cells
Measured: Baseline
Number of Participants With Mutations in Key Oncogenes at Baseline
Determination/estimation of the frequency of mutations (total and non-synonymous) present in baseline tumor derived nucleic acid samples and in baseline circulating tumor DNA.
Measured: Baseline
EuroQol Group 5-Dimension 5-Level (EQ-5D-5L) Score
The EuroQol EQ-5D-5L was a 6 item participant-completed questionnaire designed to assess health status in terms of a single index value or utility score. There are 2 components to the EQ-5D-5L, a Health State Profile which had individuals rate their level of problems (none, slight, moderate, severe, extreme/unable) in 5 areas (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), and a Visual Analogue Scale (VAS) in which participants rate their overall health status from 0 (worst imaginable) to 100 (best imaginable). Published weights were available that allow for imputation of the index score. Overall index scores ranged from 0 to 1, with low scores representing a higher level of dysfunction.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Aug 2018
- Study start19 Jul 2018
- Primary completion22 Dec 2021
- Study completion22 Dec 2021
Why it stopped: Phase 3 B9991010 study was stopped due to futility of efficacy at interim analysis on 21Dec2018, and approvals of PARP inhibitors in front-line maintenance setting, Pfizer decided stopping enrollment in the B9991030 study on 19Mar2019.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Ovarian CancerStudies of the same condition, open and under way.
- More trials run by PfizerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 79 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pfizer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Pfizer CT.gov Call Center, Study director, Pfizer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03642132
- Sponsor's protocol ID
- B9991030
- Other IDs
- 2017-004456-30, B9991030, JAVELIN OVARIAN PARP 100, 2017
- Status last verified
- Mar 2023
- First submitted
- 13 Jul 2018
- Last updated
- 6 Apr 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
Gaitskell K, Rogozinska E, Platt S, Chen Y, Abd El Aziz M, Tattersall A, Morrison J. Angiogenesis inhibitors for the treatment of epithelial ovarian cancer. Cochrane Database Syst Rev. 2023 Apr 18;4(4):CD007930. doi: 10.1002/14651858.CD007930.pub3.
PubMed 37185961
Study at a glance
From the registry record, last updated by the sponsor on 6 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT03642132
- Acronym / sponsor ID
- B9991030
- Conditions
- Ovarian Cancer
- Keywords
- untreated epithelial ovarian cancer, fallopian tube cancer, primary peritoneal cancer
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Phase 3 B9991010 study was stopped due to futility of efficacy at interim analysis on 21Dec2018, and approvals of PARP inhibitors in front-line maintenance setting, Pfizer decided stopping enrollment in the B9991030 study on 19Mar2019.
- Enrolment
- 79 participants (actual)
- Lead sponsor
- PfizerIndustry (pharma, biotech, devices)
- Study start
- 19 Jul 2018 (actual)
- Primary completion
- 22 Dec 2021 (actual)
- Study completion
- 22 Dec 2021 (actual)
- First posted
- 22 Aug 2018 (actual)
- Results
- Posted 6 Apr 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| chemotherapy, avelumab and talazoparib | Experimental | Drug: Chemotherapy + avelumab followed by avelumab + talazoparibPlatinum-based chemotherapy + avelumab followed by avelumab + talazoparib maintenance |
| chemotherapy, and talazoparib | Experimental | Drug: Chemotherapy followed by talazoparib maintenancePlatinum-based chemotherapy followed by talazoparib maintenance |
| chemotherapy and bevacizumab | Active comparator | Drug: Chemotherapy + bevacizumab followed by bevacizumabPlatinum-based chemotherapy + bevacizumab followed by bevacizumab maintenance |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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.
- 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
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Chemotherapy + avelumab followed by avelumab + talazoparibChemotherapy Period Paclitaxel Carboplatin Avelumab Maintenance Period Avelumab Talazoparib | Drug | chemotherapy, avelumab and talazoparib |
| Chemotherapy followed by talazoparib maintenanceChemotherapy Period Paclitaxel Carboplatin Maintenance Period Talazoparib | Drug | chemotherapy, and talazoparib |
| Chemotherapy + bevacizumab followed by bevacizumabChemotherapy Period Paclitaxel Carboplatin Bevacizumab Maintenance Period Bevacizumab | Drug | chemotherapy and bevacizumab |
Primary outcome
Progression-free Survival (Participants With Newly Diagnosed Advanced Ovarian Cancer With Defects in DDR+）
Time frame: 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
Progression-free survival (PFS) was defined as the time from randomization to the date of the first documentation of objective progressive disease (PD) or death due to any cause, whichever occurred first. PD: >=20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to relative increase of 20%, sum must also demonstrate an absolute increase of at least 5mm, appearance of one or more new lesions was considered PD.
16 secondary outcomes
Number of Participants With Treatment-Emergent Adverse Events (On-Treatment Period)
Time frame: 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)
Number of Participants With ADA Against Avelumab by Never and Ever Positive Status
Time frame: 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.
Pre-dose/Trough Concentration (Ctrough) for Avelumab (Chemotherapy Period)
Time frame: Day 1 of Cycles 1, 2, 3, and 4 in the chemotherapy period (1 cycle = 3 weeks)
Pre-dose/Trough Concentration (Ctrough) for Avelumab (Maintenance Period)
Time frame: 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.
Cmax for Avelumab (Chemotherapy Period)
Time frame: Day 1 of Cycles 1, 2, 3, and 4 in the chemotherapy period (1 cycle = 3 weeks)
Cmax for Avelumab (Maintenance Period)
Time frame: 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.
Ctrough for Talazoprib (Maintenance Period)
Time frame: Pre-dose on Days 1, 15 and 29 of Cycle 1
Overall Survival (Participants of Both DDR+ and Unselected DDR Status)
Time frame: From 9 weeks up to approximately 3.5 years
Progression-free Survival (Participants of Unselected DDR Status)
Time frame: 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.
Progression-free Survival (Participants of Both DDR+ and Unselected DDR Status)
Time frame: 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.
Progression-free Survival on Next-line Therapy. (Participants of Both DDR+ and Unselected DDR Status)
Time frame: 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.
PFS Per Gynecological Cancer Intergroup Criteria (Participants of Both DDR+ and Unselected DDR Status)
Time frame: From screening until death, end of study, or participant withdrawal of consent, whichever occurred first, up to approximately 3.5 years.
Functional Assessment of Ovarian Symptom Index-18 (FOSI-18) Score
Time frame: 3 years
Programmed Death Receptor-1 Ligand-1 (PD-L1) Biomarker Expression in Tumor and Immune Cells as Assessed by Immunohistochemistry (IHC) at Baseline
Time frame: Baseline
Number of Participants With Mutations in Key Oncogenes at Baseline
Time frame: Baseline
EuroQol Group 5-Dimension 5-Level (EQ-5D-5L) Score
Time frame: 3 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Apr 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37185961Gaitskell K, Rogozinska E, Platt S, Chen Y, Abd El Aziz M, Tattersall A, Morrison J. Angiogenesis inhibitors for the treatment of epithelial ovarian cancer. Cochrane Database Syst Rev. 2023 Apr 18;4(4):CD007930. doi: 10.1002/14651858.CD007930.pub3.
- To obtain contact information for a study center near you, click here.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pfizer CT.gov Call Center study director
Pfizer
72 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Chemotherapy + avelumab followed by avelumab + talazoparib, Chemotherapy followed by talazoparib maintenance and Chemotherapy + bevacizumab followed by bevacizumab in people with Ovarian Cancer, run by Pfizer at 72 sites in 10 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 6 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 72 sites in United States, Singapore, South Korea, Taiwan, Australia and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Apr 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free Survival (Participants With Newly Diagnosed Advanced Ovarian Cancer With Defects in DDR+） (time frame: 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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03642132, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Apr 2023.