The Study Evaluating Efficacy And Tolerability Of Veliparib in Combination With Temozolomide or In Combination With Carboplatin and Paclitaxel Versus Placebo in Subjects With BRCA1 and BRCA2 Mutation and Metastatic Breast Cancer

Tracking Information
First Submitted Date ICMJE	January 6, 2012
First Posted Date ICMJE	January 10, 2012
Last Update Posted Date	February 14, 2018
Actual Study Start Date ICMJE	January 23, 2012
Estimated Primary Completion Date	August 10, 2018 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: January 9, 2012)	Progression -Free Survival [ Time Frame: Radiographic evaluation every 9 weeks, clinical evaluation every cycle ]
Original Primary Outcome Measures ICMJE	Same as current
Change History	Complete list of historical versions of study NCT01506609 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: April 4, 2013)	Overall Survival [ Time Frame: From Cycle 1 Day 1 until patient's death or 3 years post discontinuation ]; Clinical Benefit Rate (CBR) [ Time Frame: From Cycle 1 Day1 until patient's death or 3 years post discontinuation ]; Objective Response Rate [ Time Frame: From Cycle 1 Day 1 until patient's death or 3 years post discontinuation ]
Original Secondary Outcome Measures ICMJE; (submitted: January 9, 2012)	Overall Survival [ Time Frame: From Randomization until patient's death or 3 years post discontinuation ]; Clinical Benefit Rate (CBR) [ Time Frame: From Randomization until patient's death or 3 years post discontinuation ]; Objective Response Rate [ Time Frame: From Randomization until patient's death or 3 years post discontinuation ]
Current Other Outcome Measures ICMJE; (submitted: April 4, 2013)	Chemotherapy-Induced Peripheral Neuropathy (CIPN) [ Time Frame: From Cycle 1 Day 1 for subjects on the carboplatin and paclitaxel treatment arm, through 30 Day Follow-up Visit. ]; CIPN (as assessed by the EORTC QLQ-CIPN20 questionnaire and NCI-CTCAE 4.0 grading for peripheral neuropathy
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	The Study Evaluating Efficacy And Tolerability Of Veliparib in Combination With Temozolomide or In Combination With Carboplatin and Paclitaxel Versus Placebo in Subjects With BRCA1 and BRCA2 Mutation and Metastatic Breast Cancer
Official Title ICMJE	A Randomized, Phase 2 Study of the Efficacy and Tolerability of Veliparib in Combination With Temozolomide or Veliparib in Combination With Carboplatin and Paclitaxel Versus Placebo Plus Carboplatin and Paclitaxel in Subjects With BRCA1 or BRCA2 Mutation and Metastatic Breast Cancer
Brief Summary	The Study Evaluating Efficacy And Tolerability of Veliparib in Combination with Temozolomide or Veliparib/Placebo in Combination with Carboplatin and Paclitaxel in Subjects with locally recurrent Breast Cancer not amenable to therapy with curative intent, or metastatic breast cancer and a documented (BRCA1) and (BRCA2) deleterious germline mutation.
Detailed Description	Subjects will be randomized in a 1:1:1 ratio to one of the three treatment groups. The safety of each treatment group will be assessed by evaluating study drug exposure, adverse events, serious adverse events, all deaths, changes in laboratory determinations, and vital sign parameters. The Clinical Benefit Rate (CBR) and Objective Response Rate (ORR) as well as Progression-free survival (PFS) using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 will be assessed. Study visits will be conducted according to the protocol schedule and randomization group. Study visits will include physical examination, laboratory blood sample collection, and assessment of vital signs, medical history and urinalysis. 12-lead Electrocardiogram (ECG) will be performed at protocol specified visits.
Study Type ICMJE	Interventional
Study Phase	Phase 2
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
Condition ICMJE	Metastatic Breast Cancer
Intervention ICMJE	Drug: Placebo Placebo comparator for Veliparib days 1 through 7 of 21-day cycle (in combination with carboplatin and/or paclitaxel).; Drug: Veliparib Days 1 through 7 of 28-day cycle (in combination with Temozolomide) or Days 1 through 7 of 21-day cycle (in combination with Carboplatin and Paclitaxel). Other Name: ABT-888; Drug: Carboplatin Day 3 of 21-day cycle; Drug: Temozolomide Days 1 through 5 of 28-day cycle (in combination with veliparib). Other Name: Temodal; Drug: Paclitaxel Day 3 of 21-day cycle. Other Name: Taxol
Study Arms	Experimental: Veliparib with Temozolomide Veliparib on Day 1 thru 7 and temozolomide on Day 1 thru 5 of a 28-day cycle. Interventions: Drug: Veliparib Drug: Temozolomide; Placebo Comparator: Placebo with Carboplatin and Paclitaxel Placebo on Day 1 thru 7 and carboplatin/paclitaxel on Day 3 of a 21-day cycle. Interventions: Drug: Placebo Drug: Carboplatin Drug: Paclitaxel; Experimental: Veliparib with Carboplatin and Paclitaxel Veliparib on Day 1 thru 7 and carboplatin/paclitaxel on Day 3 of a 21-day cycle. Interventions: Drug: Veliparib Drug: Carboplatin Drug: Paclitaxel
Publications *	Han HS, Diéras V, Robson M, Palácová M, Marcom PK, Jager A, Bondarenko I, Citrin D, Campone M, Telli ML, Domchek SM, Friedlander M, Kaufman B, Garber JE, Shparyk Y, Chmielowska E, Jakobsen EH, Kaklamani V, Gradishar W, Ratajczak CK, Nickner C, Qin Q, Qian J, Shepherd SP, Isakoff SJ, Puhalla S. Veliparib with temozolomide or carboplatin/paclitaxel versus placebo with carboplatin/paclitaxel in patients with BRCA1/2 locally recurrent/metastatic breast cancer: randomized phase II study. Ann Oncol. 2018 Jan 1;29(1):154-161. doi: 10.1093/annonc/mdx505.; Isakoff SJ, Puhalla S, Domchek SM, Friedlander M, Kaufman B, Robson M, Telli ML, Diéras V, Han HS, Garber JE, Johnson EF, Maag D, Qin Q, Giranda VL, Shepherd SP. A randomized Phase II study of veliparib with temozolomide or carboplatin/paclitaxel versus placebo with carboplatin/paclitaxel in BRCA1/2 metastatic breast cancer: design and rationale. Future Oncol. 2017 Feb;13(4):307-320. doi: 10.2217/fon-2016-0412. Epub 2016 Oct 14.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Active, not recruiting
Actual Enrollment ICMJE; (submitted: February 12, 2018)	294
Original Estimated Enrollment ICMJE; (submitted: January 9, 2012)	240
Estimated Study Completion Date	August 10, 2018
Estimated Primary Completion Date	August 10, 2018 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: Histologically or cytologically confirmed breast cancer that is either locally recurrent or metastatic.; Locally recurrent disease must not be amenable to surgical resection or radiation with curative intent.; Must have a documented deleterious Breast Cancer Gene BRCA1 or BRCA2 germline mutation.; If Human Epidermal Growth Factor Receptor (HER2) positive, subjects must have received and progressed on at least one prior standard HER2 directed therapy or the subject must be ineligible to receive anti-HER2 therapy.; Measurable or non-measurable (but radiologically evaluable) disease by RECIST (Response Evaluation Criteria in Solid Tumors) criteria 1.1.; Eastern Cooperative Oncology Group (ECOG) Performance Score of 0-2.; Subject must have adequate bone marrow, renal and hepatic function.; Subject must not be pregnant or plan to conceive a child. Exclusion Criteria: Received anticancer agent(s) or an investigational agent within 21 days prior to C1D1, or radiotherapy within 28 days prior Cycle 1 Day 1; More than 2 prior lines of cytotoxic chemotherapy; Prior treatment of breast cancer with temozolomide, a platinum agent, or a Poly (ADP ribose) Polymerase (PARP) inhibitor.; Prior taxane therapy for metastatic breast cancer.; A history of or evidence of brain metastases or leptomeningeal disease.; A history of uncontrolled seizure disorder; Pre-existing neuropathy from any cause in excess of Grade 1; Known history of allergic reaction to cremophor/paclitaxel; Clinical significant uncontrolled conditions â€" active infection, myocardial infarction, stroke, or transient ischemic attack, psychiatric illness/social situations that would limit compliance.; Pregnant or breastfeeding
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years to 99 Years (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Argentina, Australia, Belgium, Brazil, Canada, Czechia, Denmark, Finland, France, Hungary, Israel, Netherlands, Norway, Poland, Romania, Russian Federation, Spain, Sweden, Ukraine, United States
Removed Location Countries	Czech Republic, Slovakia
Administrative Information
NCT Number ICMJE	NCT01506609
Other Study ID Numbers ICMJE	M12-895; 2011-002913-12 ( EudraCT Number )
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Studies a U.S. FDA-regulated Drug Product: Yes Studies a U.S. FDA-regulated Device Product: No Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement	Plan to Share IPD: Undecided
Responsible Party	AbbVie
Study Sponsor ICMJE	AbbVie
Collaborators ICMJE	Not Provided
Investigators ICMJE	Study Director: AbbVie Inc. AbbVie
PRS Account	AbbVie
Verification Date	February 2018
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP