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

Sponsor

Pfizer (Industry)

Overall Status

Completed

CT.gov ID

NCT03642132

Collaborator

(none)

Enrollment

Locations

Arms

41.1

Actual Duration (Months)

1.1

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Ovarian Cancer	Drug: Chemotherapy + avelumab followed by avelumab + talazoparib Drug: Chemotherapy followed by talazoparib maintenance Drug: Chemotherapy + bevacizumab followed by bevacizumab	Phase 3

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

Study Type:

Interventional

Actual Enrollment :

79 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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)

Actual Study Start Date :

Jul 19, 2018

Actual Primary Completion Date :

Dec 22, 2021

Actual Study Completion Date :

Dec 22, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: chemotherapy, avelumab and talazoparib Platinum-based chemotherapy + avelumab followed by avelumab + talazoparib maintenance	Drug: Chemotherapy + avelumab followed by avelumab + talazoparib Chemotherapy Period Paclitaxel Carboplatin Avelumab Maintenance Period Avelumab Talazoparib
Experimental: chemotherapy, and talazoparib Platinum-based chemotherapy followed by talazoparib maintenance	Drug: Chemotherapy followed by talazoparib maintenance Chemotherapy Period Paclitaxel Carboplatin Maintenance Period Talazoparib
Active Comparator: chemotherapy and bevacizumab Platinum-based chemotherapy + bevacizumab followed by bevacizumab maintenance	Drug: Chemotherapy + bevacizumab followed by bevacizumab Chemotherapy Period Paclitaxel Carboplatin Bevacizumab Maintenance Period Bevacizumab

Arm

Intervention/Treatment

Experimental: chemotherapy, avelumab and talazoparib

Platinum-based chemotherapy + avelumab followed by avelumab + talazoparib maintenance

Drug: Chemotherapy + avelumab followed by avelumab + talazoparib

Chemotherapy Period Paclitaxel Carboplatin Avelumab Maintenance Period Avelumab Talazoparib

Experimental: chemotherapy, and talazoparib

Platinum-based chemotherapy followed by talazoparib maintenance

Drug: Chemotherapy followed by talazoparib maintenance

Chemotherapy Period Paclitaxel Carboplatin Maintenance Period Talazoparib

Active Comparator: chemotherapy and bevacizumab

Platinum-based chemotherapy + bevacizumab followed by bevacizumab maintenance

Drug: Chemotherapy + bevacizumab followed by bevacizumab

Chemotherapy Period Paclitaxel Carboplatin Bevacizumab Maintenance Period Bevacizumab

Outcome Measures

Primary Outcome Measures

Progression-Free Survival (PFS) - (Obsolete after effectiveness of protocol amendment 2) [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.

Secondary Outcome Measures

Overall Survival (OS) - (Obsolete after effectiveness of protocol amendment 2) [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) [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) [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) [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) [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) [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) [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).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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.

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.
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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arizona Oncology Associates, PC - HAL	Phoenix	Arizona	United States	85016
2	Arizona Oncology Associates, PC - HAL	Phoenix	Arizona	United States	85027
3	Arizona Oncology Associates, PC - HAL	Scottsdale	Arizona	United States	85258
4	Arizona Oncology Associates, PC - HAL	Tempe	Arizona	United States	85284
5	Arizona Oncology Associates, PC - HOPE	Tucson	Arizona	United States	85704
6	Arizona Oncology Associates, PC - HOPE	Tucson	Arizona	United States	85711
7	Sansum Clinic	Santa Barbara	California	United States	93105
8	Sansum Clinic	Solvang	California	United States	93463
9	Smilow Cancer Hospital at Yale-New Haven	New Haven	Connecticut	United States	06510
10	Montefiore Medical Center - EPC	Bronx	New York	United States	10461
11	Montefiore Medical Center, Department of Obstetrics and Gynecology and Women's Health	Bronx	New York	United States	10461
12	Montefiore Medical Center	Bronx	New York	United States	10461
13	Montefiore Medical Center-Centennial Facility	Bronx	New York	United States	10467
14	NYU Winthrop Hospital, Gynecologic Oncology	Mineola	New York	United States	11501
15	NYU Winthrop Hospital, Infusion Center	Mineola	New York	United States	11501
16	NYU Winthrop Radiology	Mineola	New York	United States	11501
17	Oncology Hematology Care, Inc.	Cincinnati	Ohio	United States	45211
18	Oncology Hematology Care Inc	Cincinnati	Ohio	United States	45230
19	Oncology Hematology Care Inc	Cincinnati	Ohio	United States	45236
20	Oncology Hematology Care, Inc.	Cincinnati	Ohio	United States	45242
21	Northwest Cancer Specialists, P.C.	Portland	Oregon	United States	97213-2982
22	Northwest Cancer Specialists, P.C.	Portland	Oregon	United States	97225
23	Northwest Cancer Specialists, P.C.	Portland	Oregon	United States	97227
24	Northwest Cancer Specialists, P.C.	Tualatin	Oregon	United States	97062
25	Tennessee Oncology, PLLC	Dickson	Tennessee	United States	37055
26	Tennessee Oncology, PLLC	Franklin	Tennessee	United States	37067
27	Tennessee Oncology, PLLC	Gallatin	Tennessee	United States	37066
28	Tennessee Oncology, PLLC	Hermitage	Tennessee	United States	37076
29	Tennessee Oncology, PLLC	Lebanon	Tennessee	United States	37090
30	Tennessee Oncology, PLLC	Murfreesboro	Tennessee	United States	37129
31	Tennessee Oncology, PLLC	Nashville	Tennessee	United States	37203
32	The Sarah Cannon Research Institute	Nashville	Tennessee	United States	37203
33	Tennessee Oncology, PLLC	Nashville	Tennessee	United States	37205
34	Tennessee Oncology, PLLC	Nashville	Tennessee	United States	37207
35	Tennessee Oncology, PLLC	Nashville	Tennessee	United States	37211
36	Tennessee Oncology, PLLC	Shelbyville	Tennessee	United States	37160
37	Tennessee Oncology, PLLC	Smyrna	Tennessee	United States	37167
38	Texas Oncology Bedford	Bedford	Texas	United States	76022
39	Texas Oncology	Fort Worth	Texas	United States	76104
40	US Oncology Investigational Products Center (IPC)	Irving	Texas	United States	75063
41	US Oncology Investigational Products Center	Irving	Texas	United States	75063
42	Texas Oncology- San Antonio	San Antonio	Texas	United States	78240
43	Virginia Oncology Associates	Chesapeake	Virginia	United States	23320
44	Virginia Oncology Associates	Norfolk	Virginia	United States	23502
45	Virginia Oncology Associates	Virginia Beach	Virginia	United States	23456
46	Northwest Cancer Specialists, P.C.	Vancouver	Washington	United States	98684
47	Epworth Foundation trading as Epworth HealthCare	East Melbourne	Victoria	Australia	3002
48	Epworth HealthCare, Clinical Trials & Research Centre	Richmond	Victoria	Australia	3121
49	CHU-UCL Namur/Site Sainte Elisabeth	Namur		Belgium	5000
50	Bon Secours Hospital	Cork		Ireland	T12 DV56
51	Istituto Europeo di Oncologia (IEO)	Milano	MI	Italy	20141
52	Fondazione Policlinico Universitario A. Gemelli IRCCS	Roma	RM	Italy	00168
53	Niigata Cancer Center Hospital	Niigata		Japan	951-8566
54	Korea University Anam Hospital	Seoul		Korea, Republic of	02841
55	Severance Hospital, Yonsei University Health System	Seoul		Korea, Republic of	03722
56	Asan Medical Center	Seoul		Korea, Republic of	05505
57	Gangnam Severance Hospital	Seoul		Korea, Republic of	06229
58	Gangnam Severance Hospital	Seoul		Korea, Republic of	06273
59	Clinical Trial Pharmacy, Samsung Medical Center	Seoul		Korea, Republic of	06351
60	Samsung Medical Center	Seoul		Korea, Republic of	06351
61	Limited Liability Company "VitaMed" (LLC "VitaMed")	Moscow		Russian Federation	121309
62	Department of Nuclear Medicine and Molecular Imaging	Singapore		Singapore	169608
63	SingHealth Investigational Medicine Unit	Singapore		Singapore	169608
64	National Cancer Centre Singapore	Singapore		Singapore	169610
65	Department of Pathology	Singapore		Singapore	169856
66	Raffles Hospital	Singapore		Singapore	188770
67	Raffles Radiology	Singapore		Singapore	188770
68	Farrer Park Hospital	Singapore		Singapore	217562
69	Taipei Veterans General Hospital	Taipei		Taiwan	11217
70	Department of Radiology, Koo Foundation Sun Yat-Sen Cancer Center	Taipei		Taiwan	112
71	Division of Pharmacy, Koo Foundation Sun Yat-Sen Cancer Center	Taipei		Taiwan	112
72	Koo Foundation Sun Yat-Sen Cancer Center	Taipei		Taiwan	112