Veliparib With Carboplatin and Paclitaxel and as Continuation Maintenance Therapy in Adults With Newly Diagnosed Stage III or IV, High-grade Serous, Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

Ovarian Cancer Clinical Trial

— VELIA  

Official title:

A Phase 3 Placebo-Controlled Study of Carboplatin/Paclitaxel With or Without Concurrent and Continuation Maintenance Veliparib (PARP Inhibitor) in Subjects With Previously Untreated Stages III or IV High-Grade Serous Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02470585
• Other study ID #: M13-694
• Secondary ID: 2014-005070-11
• Status: Terminated
• Phase: Phase 3
• Start date: June 29, 2015
• Est. completion date: October 5, 2023

Study information

• Verified date: June 2023
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective of the study was to evaluate whether progression-free survival (PFS) was prolonged with the addition of veliparib to standard platinum-based chemotherapy (carboplatin/paclitaxel [C/P]) and continued as maintenance therapy compared with chemotherapy alone.

Description:

Participants were randomized in a 1:1:1 ratio to one of three arms. Randomization in the entire population was stratified according to the timing of surgery and residual disease status (any residual disease after primary surgery vs. no residual disease after primary surgery vs. interval surgery) and the paclitaxel schedule (weekly vs. every 3 -weeks), stage of disease (III vs. IV), geographic region (Japan vs. North America and rest of world [ROW]), and germline breast cancer susceptibility gene (BRCA) mutation status (positive versus negative or Unknown).

Cytoreductive surgery could be performed before randomization and the initiation of study treatment (primary) or after 3 cycles of study treatment (interval). The weekly or every-3-week paclitaxel schedule and the choice of primary or interval cytoreductive surgery were determined at the discretion of the investigator.

The primary objective was evaluated in the BRCA-deficient cohort, participants with homologous recombination deficiency (HRD), and the intention-to-treat (ITT) population. These populations were sequentially inclusive, with the HRD population including the BRCA-deficient population, and the ITT population including the HRD and BRCA-deficient populations. The BRCA-deficient population was defined as participants with either a germline (gBRCA) and/or tissue-based (tBRCA) deleterious or suspected deleterious mutation in BRCA1 or BRCA2 confirmed by centralized testing. The HRD population was defined as participants with HRD tumors based on HRD score or presence of a deleterious or suspected deleterious mutation in BRCA1 or BRCA2 as determined by centralized testing.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1140
• Est. completion date: October 5, 2023
• Est. primary completion date: May 3, 2019
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Histologic diagnosis of International Federation of Gynecology and Obstetrics (FIGO) Stage III or IV epithelial ovarian, fallopian tube, or primary peritoneal carcinoma, with the appropriate tissue available for histologic evaluation.

2. High-grade serous adenocarcinoma

3. Willing to undergo testing for gBRCA.

4. Adequate hematologic, renal, and hepatic function.

5. Neuropathy (sensory and motor) less than or equal to Grade 1.

6. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.

7. Participants who undergo primary cytoreductive surgery must be entered between 1 and 12 weeks after surgery. Participants undergoing interval surgery must have a tumor sample confirming the histological diagnosis prior to enrollment.

8. Participants with measurable disease or non-measurable disease are eligible. Participants may or may not have cancer-related symptoms.

9. Participant has one of the following available for pharmacodynamic analyses including somatic BRCA testing: Archived diagnostic formalin-fixed paraffin embedded (FFPE) tumor tissue; or tumor tissue biopsy collected prior to Cycle 1 Day 1.

Exclusion Criteria:

1. Endometrioid adenocarcinoma, carcinosarcoma, undifferentiated carcinoma, mixed epithelial adenocarcinoma, adenocarcinoma not otherwise specified, mucinous adenocarcinoma, clear cell adenocarcinoma, low-grade serous adenocarcinoma, or malignant Brenner's tumor.

2. Participants with synchronous primary endometrial cancer, or a past history of endometrial cancer unless all of the following conditions are met: endometrial cancer stage not greater than IA, no vascular or lymphatic invasion, no poorly differentiated subtypes including serous, clear cell, or other FIGO grade 3 lesions.

3. Participants with any evidence of other invasive malignancy being present within the last 3 years (with the exception of non-melanoma skin cancer). Participants are also excluded if their previous cancer treatment contraindicates this protocol's therapy.

4. Received prior radiotherapy to any portion of the abdominal cavity or pelvis.

5. Received prior chemotherapy for any abdominal or pelvic tumor.

6. Clinically significant uncontrolled condition(s).

7. Known history of allergic reaction to Cremophor-paclitaxel, carboplatin, Azo-Colourant Tartrazine (also known as FD&C Yellow 5 or E102), Azo-Colourant Orange Yellow-S (also known as FD&C Yellow 6 or E110) or known contraindications to any study supplied drug.

8. History or evidence upon physical examination of central nervous system (CNS) disease, including primary brain tumor, any brain metastases, or history of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) within 6 months of Cycle 1 Day 1.

Related Conditions & MeSH terms

• Ovarian Cancer
• Ovarian Neoplasm
• Ovarian Neoplasms

Intervention

Drug:
• Veliparib
Capsules for oral administration
• Paclitaxel
Administered by intravenous infusion, either 80 mg/m² of body-surface area (BSA) on Days 1, 8, and 15 of each 21-day cycle (weekly dosing), or 175 mg/m² of BSA on Day 1 of each 21-day cycle (3-week dosing).
• Carboplatin
Administered by intravenous infusion at an area under the curve (AUC) of 6 mg/mL/min every 3 weeks.

Other:
• Placebo to Veliparib
Capsules for oral administration

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital /ID# 150071	Adelaide	South Australia
Australia	Monash Health /ID# 145297	Clayton	Victoria
Australia	Coffs Harbour Health Campus /ID# 145132	Coffs Harbour	New South Wales
Australia	The Townsville Hospital /ID# 149163	Douglas	Queensland
Australia	Gosford Hospital /ID# 145299	Gosford	New South Wales
Australia	Royal Brisbane and Women's Hospital /ID# 145135	Herston	Queensland
Australia	St George Hospital /ID# 145138	Kogarah	New South Wales
Australia	Newcastle Private Hospital /ID# 145834	Lambton Heights	New South Wales
Australia	Cabrini Health /ID# 145142	Malvern	Victoria
Australia	Sir Charles Gairdner Hospital /ID# 145140	Nedlands	Western Australia
Australia	Royal Womens Hospital /ID# 145136	Parkville	Victoria
Australia	The Prince of Wales Hospital /ID# 145134	Randwick	New South Wales
Australia	Icon Cancer Centre /ID# 148208	South Brisbane	Queensland
Australia	Mater Misericordiae Limited /ID# 145682	South Brisbane	Queensland
Australia	Northern Cancer Institute /ID# 145681	St Leonards	New South Wales
Australia	St. John of God Subiaco Hosp /ID# 147742	Subiaco	Western Australia
Australia	Calvary Mater Newcastle /ID# 145139	Waratah	New South Wales
Australia	Westmead Hospital /ID# 145137	Westmead	New South Wales
Australia	Southern Medical Day Care Ctr /ID# 145133	Wollongong	New South Wales
Brazil	Hospital de Cancer de Barretos /ID# 137121	Barretos	Sao Paulo
Brazil	Hc Ufmg /Id# 137156	Belo Horizonte	Minas Gerais
Brazil	Hospital Sao Lucas da PUCRS /ID# 137157	Porto Alegre	Rio Grande Do Sul
Brazil	Instituto Nacional de Câncer José de Alencar Gomes da Silva (INCA) /ID# 137155	Rio de Janeiro
Brazil	Centro de Referencia da Saude da Mulher - Hospital Perola Byington /ID# 137120	São Paulo	Sao Paulo
Denmark	Regionshospitalet Herning /ID# 137260	Herning
Denmark	Vejle Sygehus /ID# 137262	Vejle	Syddanmark
Israel	Rambam Health Care Campus /ID# 137434	Haifa
Israel	The Lady Davis Carmel MC /ID# 137537	Haifa
Israel	Shaare Zedek Medical Center /ID# 137435	Jerusalem
Israel	Meir Medical Center /ID# 139397	Kfar Saba
Israel	Sheba Medical Center /ID# 137436	Ramat Gan
Israel	Kaplan Medical Center /ID# 137536	Rehovot
Japan	Hyogo Cancer Center /ID# 148327	Akashi
Japan	Kansai Rosai Hospital /ID# 149237	Amagasaki
Japan	National Hospital Organization Kyushu Cancer Center /ID# 149133	Fukuoka-shi	Fukuoka
Japan	The Jikei Univ. Kashiwa Hosp. /ID# 149238	Kashiwa-shi
Japan	St. Marianna Univ Hospital /ID# 149327	Kawasaki
Japan	The Cancer Institute Hosp JFCR /ID# 148436	Koto-ku	Tokyo
Japan	Kumamoto University Hospital /ID# 154169	Kumamoto-shi	Kumamoto
Japan	NHO Kure Medical Center and Ch /ID# 148569	Kure
Japan	Kurume University Hospital /ID# 148697	Kurume-shi	Fukuoka
Japan	Shikoku Cancer Center /ID# 148382	Matsuyama
Japan	Aichi Cancer Center Hospital /ID# 148398	Nagoya-shi	Aichi
Japan	Niigata University Medical & Dental Hospital /ID# 149488	Niigata-shi	Niigata
Japan	Osaka International Cancer Institute /ID# 150778	Osaka
Japan	Kindai University Hospital /ID# 154947	Osaka-sayama	Osaka
Japan	Hokkaido Cancer Center /ID# 148570	Sapporo
Japan	Tohoku University Hospital /ID# 149818	Sendai-shi	Miyagi
Japan	Keio University Hospital /ID# 148326	Shinjuku-ku	Tokyo
Japan	Iwate Medical University Hospital /ID# 147721	Shiwa-gun	Iwate
Japan	Shizuoka Cancer Center /ID# 147723	Sunto-gun	Shizuoka
Japan	The Jikei University Hospital /ID# 148691	Tokyo
Japan	Mie University Hospital /ID# 149169	Tsu-shi	Mie
Japan	Yamagata University Hospital /ID# 153646	Yamagata-shi	Yamagata
Korea, Republic of	Korea University Anam Hospital /ID# 136908	???	Gyeonggido
Korea, Republic of	National Cancer Center /ID# 139404	Goyang	Gyeonggido
Korea, Republic of	Asan Medical Center /ID# 136836	Seoul
Korea, Republic of	Gangnam Severance Hospital /ID# 136835	Seoul	Seoul Teugbyeolsi
Korea, Republic of	Samsung Medical Center /ID# 136834	Seoul	Seoul Teugbyeolsi
Korea, Republic of	Seoul National University Hospital /ID# 136909	Seoul
New Zealand	Auckland City Hospital /ID# 145123	Auckland
Poland	Uniwersyteckie C. Kliniczne /ID# 138021	Gdansk
Spain	Hospital Clinic de Barcelona /ID# 137300	Barcelona
Spain	Hospital Univ Vall d'Hebron /ID# 137297	Barcelona
Spain	Hospital Duran i Reynals /ID# 137298	L'Hospitalet de Llobregat	Barcelona
Spain	Hosp Univ 12 de Octubre /ID# 137299	Madrid
Spain	Hosp Univ Madrid Sanchinarro /ID# 137414	Madrid
Spain	Hospital Clin Univ San Carlos /ID# 137402	Madrid
Spain	Fundacion Inst Valenciano Onc /ID# 137403	Valencia
United Kingdom	Ninewells Hospital /ID# 137967	Dundee
United Kingdom	Beatson west of scotland cancer center /ID# 137965	Glasgow	Scotland
United Kingdom	James Paget University Hosp /ID# 137970	Great Yarmouth
United Kingdom	Imanova Limited, Hammersmith Hospital /ID# 137966	London
United Kingdom	Norfolk and Norwich Univ Hosp /ID# 137969	Norwich	Norfolk
United Kingdom	Oxford Univ Hosp NHS Trust /ID# 137973	Oxford
United States	Abington Memorial Hospital /ID# 138086	Abington	Pennsylvania
United States	Women's Cancer Care Associates /ID# 138234	Albany	New York
United States	SW Gynecologic Oncology Assoc /ID# 147097	Albuquerque	New Mexico
United States	University of New Mexico /ID# 144220	Albuquerque	New Mexico
United States	McFarland Clinic, PC /ID# 139455	Ames	Iowa
United States	Alaska Womens Cancer Care /ID# 138231	Anchorage	Alaska
United States	Hope Womens Cancer Centers /ID# 139614	Asheville	North Carolina
United States	Georgia Regents University /ID# 138085	Augusta	Georgia
United States	Kaiser Permanente, Waterpark III Institute for Health Research /ID# 139499	Aurora	Colorado
United States	Univ of Colorado Cancer Center /ID# 138016	Aurora	Colorado
United States	Texas Oncology - Austin Central /ID# 143817	Austin	Texas
United States	Texas Oncology - South Austin /ID# 143818	Austin	Texas
United States	Greater Baltimore Medical Ctr /ID# 138049	Baltimore	Maryland
United States	Sinai Hospital of Baltimore /ID# 141306	Baltimore	Maryland
United States	Texas Oncology - Bedford /ID# 143814	Bedford	Texas
United States	University of Alabama at Birmingham - Main /ID# 138087	Birmingham	Alabama
United States	Montefiore Medical Center /ID# 139585	Bronx	New York
United States	SUNY Downstate Medical Center /ID# 139533	Brooklyn	New York
United States	Roswell Park Comprehensive Cancer Center /ID# 138052	Buffalo	New York
United States	University of Vermont Medical Center /ID# 138251	Burlington	Vermont
United States	MD Anderson Cancer Ctr at Coop /ID# 139616	Camden	New Jersey
United States	Univ NC Chapel Hill /ID# 138547	Chapel Hill	North Carolina
United States	Medical University of South Carolina /ID# 138181	Charleston	South Carolina
United States	Atrium Health Carolinas Medical Center /ID# 139568	Charlotte	North Carolina
United States	Presbyterian Cancer Center /ID# 139590	Charlotte	North Carolina
United States	University of Virginia /ID# 138088	Charlottesville	Virginia
United States	Chattanoogas Program in Womens /ID# 139545	Chattanooga	Tennessee
United States	Rush University Medical Center /ID# 143491	Chicago	Illinois
United States	University of Chicago /ID# 139612	Chicago	Illinois
United States	University of Cincinnati /ID# 139619	Cincinnati	Ohio
United States	Cleveland Clinic Main Campus /ID# 139501	Cleveland	Ohio
United States	Fairview Hospital /ID# 144403	Cleveland	Ohio
United States	Univ Hosp Cleveland /ID# 139615	Cleveland	Ohio
United States	Ellis Fischel Cancer Center /ID# 139571	Columbia	Missouri
United States	Columbus NCORP /ID# 139587	Columbus	Ohio
United States	IACT Health /ID# 138058	Columbus	Georgia
United States	The Ohio State University - Columbus /ID# 138053	Columbus	Ohio
United States	John Muir Medical Center /ID# 139618	Concord	California
United States	Texas Oncology - Medical City Dallas /ID# 143809	Dallas	Texas
United States	Texas Oncology - Medical City Dallas /ID# 143812	Dallas	Texas
United States	Henry Ford Health System /ID# 139536	Detroit	Michigan
United States	Wayne State University /ID# 139601	Detroit	Michigan
United States	Duke University Medical Center /ID# 138048	Durham	North Carolina
United States	Willamette Valley Cancer Institute /ID# 140318	Eugene	Oregon
United States	NorthShore University HealthSystem - Evanston Hospital /ID# 139451	Evanston	Illinois
United States	Texas Oncology - Forth Worth /ID# 143811	Fort Worth	Texas
United States	HSHS St. Vincent Hospital /ID# 139453	Green Bay	Wisconsin
United States	Hackensack Univ Med Ctr /ID# 143776	Hackensack	New Jersey
United States	Sharma, Hinsdale, IL /ID# 140326	Hinsdale	Illinois
United States	Kapiolani Medical Center /ID# 140319	Honolulu	Hawaii
United States	The Queens Medical Center /ID# 141709	Honolulu	Hawaii
United States	Houston Methodist Hospital - Scurlock Tower /ID# 138232	Houston	Texas
United States	Memorial Hermann Hospital /ID# 138238	Houston	Texas
United States	Tennessee Valley Gyn-Onc /ID# 139548	Huntsville	Alabama
United States	Indiana Univ School Medicine /ID# 139610	Indianapolis	Indiana
United States	Saint Vincent /ID# 139537	Indianapolis	Indiana
United States	University of Iowa Hospitals and Clinics /ID# 138082	Iowa City	Iowa
United States	St. Dominic Hospital /ID# 138241	Jackson	Mississippi
United States	Univ Kansas Med Ctr /ID# 140322	Kansas City	Kansas
United States	Womens Cancer Center /ID# 138062	Kettering	Ohio
United States	Ucsd /Id# 140323	La Jolla	California
United States	Northwell Health /ID# 139572	Lake Success	New York
United States	Womens Cancer Center of Nevada /ID# 138092	Las Vegas	Nevada
United States	Dartmouth-Hitchcock Medical Center /ID# 139502	Lebanon	New Hampshire
United States	Baptist Health Lexington /ID# 139542	Lexington	Kentucky
United States	University of Kentucky Chandler Medical Center /ID# 138060	Lexington	Kentucky
United States	University of Arkansas for Medical Sciences /ID# 138253	Little Rock	Arkansas
United States	Long Beach Memorial Medical Ct /ID# 147526	Long Beach	California
United States	Kaiser Permanente /ID# 141305	Los Angeles	California
United States	University of California, Los Angeles /ID# 138179	Los Angeles	California
United States	Norton Cancer Institute /ID# 139567	Louisville	Kentucky
United States	Hillcrest Hospital /ID# 144404	Mayfield Heights	Ohio
United States	University of Miami /ID# 139457	Miami	Florida
United States	Froedtert & the Medical College of Wisconsin /ID# 139449	Milwaukee	Wisconsin
United States	University of South Alabama /ID# 138091	Mobile	Alabama
United States	Skagit Valley Medical Center /ID# 139586	Mount Vernon	Washington
United States	Hartford Healthcare /ID# 138184	New Britain	Connecticut
United States	Yale University /ID# 138056	New Haven	Connecticut
United States	Columbia University Medical Center /ID# 138252	New York	New York
United States	Icahn School of Med Mt. Sinai /ID# 139617	New York	New York
United States	Memorial Sloan Kettering Cancer Center /ID# 138017	New York	New York
United States	Memorial Sloan Kettering Cancer Center /ID# 154464	New York	New York
United States	Univ Oklahoma HSC /ID# 138020	Oklahoma City	Oklahoma
United States	Nebraska Methodist Hospital /ID# 139600	Omaha	Nebraska
United States	Medical Oncology Care Assoc /ID# 139498	Orange	California
United States	Univ CA, Irvine Med Ctr /ID# 139613	Orange	California
United States	Advocate Lutheran General Hosp /ID# 139489	Park Ridge	Illinois
United States	Fox Chase Cancer Center /ID# 149479	Philadelphia	Pennsylvania
United States	Thomas Jefferson University /ID# 138239	Philadelphia	Pennsylvania
United States	University of Pennsylvania /ID# 140079	Philadelphia	Pennsylvania
United States	University of Pittsburgh MC /ID# 138054	Pittsburgh	Pennsylvania
United States	Kaiser Permanente, NW /ID# 138249	Portland	Oregon
United States	MMP Women's Health /ID# 139544	Portland	Maine
United States	Women and Infants Hospital /ID# 138083	Providence	Rhode Island
United States	MultiCare Regional Cancer Ctr /ID# 149872	Puyallup	Washington
United States	Reading Hospital /ID# 138057	Reading	Pennsylvania
United States	Renown Regional Medical Center /ID# 138237	Reno	Nevada
United States	Carilion Roanoke Memorial Hosp /ID# 139602	Roanoke	Virginia
United States	Mayo Clinic - Rochester /ID# 139565	Rochester	Minnesota
United States	Weinberg Cancer Inst Franklin /ID# 138235	Rossville	Maryland
United States	William Beaumont Hospital /ID# 139550	Royal Oak	Michigan
United States	UC Davis Comprehensive Cancer Center - Main /ID# 144439	Sacramento	California
United States	Washington University-School of Medicine /ID# 138089	Saint Louis	Missouri
United States	Mmcorc /Id# 139534	Saint Louis Park	Minnesota
United States	Women's Cancer Associates /ID# 140321	Saint Petersburg	Florida
United States	University of Utah /ID# 138250	Salt Lake City	Utah
United States	California Pacific Medical Ctr /ID# 138177	San Francisco	California
United States	Kaiser Permanente - San Francisco /ID# 142051	San Francisco	California
United States	Univ California, San Francisco /ID# 138178	San Francisco	California
United States	Kaiser Permanente-Santa Clara /ID# 142053	Santa Clara	California
United States	Sarasota Memorial Health Care /ID# 138180	Sarasota	Florida
United States	Memorial Health Univ Med Ctr /ID# 138019	Savannah	Georgia
United States	St. Joseph's/Candler /ID# 138090	Savannah	Georgia
United States	Sanford Research/USD /ID# 139624	Sioux Falls	South Dakota
United States	Baystate Medical Center /ID# 139456	Springfield	Massachusetts
United States	Cancer Research For the Ozarks /ID# 139538	Springfield	Missouri
United States	Ferrell-Duncan Clinic /ID# 143484	Springfield	Missouri
United States	Stanford University School of Med /ID# 139450	Stanford	California
United States	Palo Alto Medical Foundation /ID# 139452	Sunnyvale	California
United States	SUNY Upstate Medical University - Downtown /ID# 139513	Syracuse	New York
United States	Multicare Institute for Research and Innovation /ID# 143485	Tacoma	Washington
United States	Moffitt Cancer Center /ID# 138061	Tampa	Florida
United States	Texas Oncology - The Woodlands /ID# 142003	The Woodlands	Texas
United States	Arizona Oncology Associates, PC-HOPE /ID# 142002	Tucson	Arizona
United States	Arizona Oncology Associates, PC-HOPE /ID# 143805	Tucson	Arizona
United States	Arizona Oncology Associates, PC-HOPE /ID# 143806	Tucson	Arizona
United States	Arizona Oncology Associates, PC-HOPE /ID# 143808	Tucson	Arizona
United States	University of Arizona Cancer Center - North Campus /ID# 138084	Tucson	Arizona
United States	University of Arizona Cancer Center - North Campus /ID# 139495	Tucson	Arizona
United States	Oklahoma Cancer Specialists /ID# 138059	Tulsa	Oklahoma
United States	Texas Oncology - Tyler /ID# 143810	Tyler	Texas
United States	Kaiser Permanente Medical Ctr-Vallejo /ID# 139492	Vallejo	California
United States	Kaiser Permanente- Walnut Creek /ID# 142052	Walnut Creek	California
United States	Wake Forest Baptist Medical Center /ID# 139588	Winston-Salem	North Carolina
United States	UMass Memorial Medical Center /ID# 139458	Worcester	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
AbbVie	Gynecologic Oncology Group;Australia New Zealand Gynaecological Oncology Group

Countries where clinical trial is conducted

United States,  Australia,  Brazil,  Denmark,  Israel,  Japan,  Korea, Republic of,  New Zealand,  Poland,  Spain,  United Kingdom, 

References & Publications (1)

Coleman RL, Fleming GF, Brady MF, Swisher EM, Steffensen KD, Friedlander M, Okamoto A, Moore KN, Efrat Ben-Baruch N, Werner TL, Cloven NG, Oaknin A, DiSilvestro PA, Morgan MA, Nam JH, Leath CA 3rd, Nicum S, Hagemann AR, Littell RD, Cella D, Baron-Hay S, Garcia-Donas J, Mizuno M, Bell-McGuinn K, Sullivan DM, Bach BA, Bhattacharya S, Ratajczak CK, Ansell PJ, Dinh MH, Aghajanian C, Bookman MA. Veliparib with First-Line Chemotherapy and as Maintenance Therapy in Ovarian Cancer. N Engl J Med. 2019 Dec 19;381(25):2403-2415. doi: 10.1056/NEJMoa1909707. Epub 2019 Sep 28. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-Free Survival (PFS) in the BRCA-deficient Population	PFS was defined as the time from the date that the participant was randomized to the date the participant experienced an event of disease progression, according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.1 (as determined by the investigator) or to the date of death if disease progression was not reached. If the participant did not have an event of disease progression or death prior to the analysis cut-off date, the participant's data were censored at the date of their last evaluable disease assessment. PFS was estimated using the Kaplan-Meier method. The analysis of PFS occurred when the protocol-specified number of PFS events was reached.; Progressive Disease (PD): At least a 20% increase in the size of target lesions, compared with the smallest size recorded since the treatment started, and an absolute increase of = 5 mm, or unequivocal progression of existing non-target lesions or the appearance of new lesions.	From randomization until the primary analysis data cut-off date of 03 May 2019, the median duration of follow-up was 28 months.
Primary	Progression-Free Survival (PFS) in the Homologous Recombination Deficiency Cohort	PFS was defined as the time from the date that the participant was randomized to the date the participant experienced an event of disease progression, according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.1 (as determined by the investigator) or to the date of death if disease progression was not reached. If the participant did not have an event of disease progression or death, the participant's data were censored at the date of their last evaluable disease assessment. PFS was estimated using the Kaplan-Meier method. The primary analysis of PFS occurred when the protocol-specified number of PFS events was reached and was performed in 3 sequentially inclusive populations.; Progressive Disease (PD): At least a 20% increase in the size of target lesions, compared with the smallest size recorded since the treatment started, and an absolute increase of = 5 mm, or unequivocal progression of existing non-target lesions or the appearance of new lesions.; .	From randomization until the primary analysis data cut-off date of 03 May 2019, the median duration of follow-up was 28 months.
Primary	Progression-Free Survival (PFS) in the Intention-to-treat Population	PFS was defined as the time from the date that the participant was randomized to the date the participant experienced an event of disease progression, according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.1 (as determined by the investigator) or to the date of death (all causes of mortality) if disease progression was not reached. If the participant did not have an event of disease progression according to RECIST criteria (as or death, the participant's data were censored at the date of their last evaluable disease assessment. PFS was estimated using the Kaplan-Meier method.; Progressive Disease (PD): At least a 20% increase in the size of target lesions, compared with the smallest size recorded since the treatment started, and an absolute increase of = 5 mm, or unequivocal progression of existing non-target lesions or the appearance of new lesions.; The primary analysis of PFS occurred when the protocol-specified number of PFS events was reached.	From randomization until the primary analysis data cut-off date of 03 May 2019, the median duration of follow-up was 28 months.
Secondary	Overall Survival (OS)	OS is defined as the time from the day the participant was randomized to the date of death. All events of death will be included, regardless of whether the event occurs while the participant is still taking study drug, or after discontinuation of study drug. If a participant has not died, then the data will be censored at the date the participant is last known to be alive.; The final analysis of OS will occur when the pre-specified number of events has occurred in the ITT and HRD populations.	Approximately 8 years from randomization.
Secondary	Change From Baseline in Disease Related Symptom (DRS) Score in the BRCA-mutation Population	The Disease Related Symptom score is a subset of the National Comprehensive Cancer Network Functional Assessment of Cancer Therapy Ovarian Symptom Index-18 (NFOSI-18), which evaluates nine symptoms related to ovarian cancer. The NFOSI-18 DRS score ranges from 0 to 36, with higher scores indicating a lower burden of symptoms and a score of 0 being severely symptomatic. A 3-point difference was defined as clinically meaningful. A positive change from Baseline indicates improvement.; Change from Baseline was calculated using a used a mixed-model for repeated measures (MMRM) with treatment, stratification factors of residual disease and stage of disease, time point and treatment-by-time point interaction as fixed effect factors, and Baseline DRS score as a covariate.; DRS was not included in the fixed-sequence testing procedure.	Baseline and Day 1 of Cycles 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, and 35
Secondary	Change From Baseline in Disease Related Symptom (DRS) Score in the HRD Population	The Disease Related Symptom score is a subset of the National Comprehensive Cancer Network Functional Assessment of Cancer Therapy Ovarian Symptom Index-18 (NFOSI-18), which evaluates nine symptoms related to ovarian cancer. The NFOSI-18 DRS score ranges from 0 to 36, with higher scores indicating a lower burden of symptoms and a score of 0 being severely symptomatic. A 3-point difference was defined as clinically meaningful. A positive change from Baseline indicates improvement.; Change from Baseline was calculated using a used a mixed-model for repeated measures (MMRM) with treatment, stratification factors of residual disease and stage of disease, time point and treatment-by-time point interaction as fixed effect factors, and Baseline DRS score as a covariate.; DRS was not included in the fixed-sequence testing procedure.	Baseline and Day 1 of Cycles 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, and 35
Secondary	Change From Baseline in Disease Related Symptom (DRS) Score in the ITT Population	The Disease Related Symptom score is a subset of the National Comprehensive Cancer Network Functional Assessment of Cancer Therapy Ovarian Symptom Index-18 (NFOSI-18), which evaluates nine symptoms related to ovarian cancer. The NFOSI-18 DRS score ranges from 0 to 36, with higher scores indicating a lower burden of symptoms and a score of 0 being severely symptomatic. A 3-point difference was defined as clinically meaningful. A positive change from Baseline indicates improvement.; Change from Baseline was calculated using a used a mixed-model for repeated measures (MMRM) with treatment, stratification factors of residual disease, stage of disease, choice of paclitaxel dosing regimen and BRCA-deficient status, time point and treatment-by-time point interaction as fixed effect factors, and Baseline DRS score as a covariate.; DRS was not included in the fixed-sequence testing procedure.	Baseline and Day 1 of Cycles 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, and 35