Study of ABT-767 in Subjects With Breast Cancer 1 and Breast Cancer 2 (BRCA 1 and BRCA 2) Mutations and Solid Tumors or High Grade Serous Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier:
NCT01339650
First received: April 4, 2011
Last updated: June 9, 2014
Last verified: June 2014
  Purpose

This is a Phase 1, dose escalation trial evaluating the tolerability, pharmacokinetics, and pharmacodynamics of ABT-767 in subjects with advanced Breast Cancer 1 or 2 gene (BRCA1 or BRCA2)-mutated solid tumors and high grade serous ovarian, fallopian tube, or primary peritoneal cancer.


Condition Intervention Phase
Fallopian Tube
Primary Peritoneal Cancer
Solid Tumors (e.g. Breast, Ovarian, Prostate, or Pancreatic) and Ovarian
Drug: ABT-767
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Factorial Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1 Study of ABT-767 in BRCA1 or BRCA2 Mutation Carriers With Advanced Solid Tumors and in Subjects With High Grade Serous Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

Resource links provided by NLM:


Further study details as provided by AbbVie:

Primary Outcome Measures:
  • Pharmacokinetic profile [ Time Frame: Various time points from Cycle 1 Day -4 to Day 8 ] [ Designated as safety issue: No ]
    Blood samples for pharmacokinetics of ABT-767 will be collected at designated time points


Secondary Outcome Measures:
  • Safety (number of subjects with adverse events and/or dose limiting toxicities) [ Time Frame: Weekly for the first two months, every other week for the third month, and monthly there after. An expected average is 5 months. ] [ Designated as safety issue: Yes ]
    Adverse events, laboratory results, physical exams and vital signs will be evaluated throughout the study.


Estimated Enrollment: 75
Study Start Date: May 2011
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ABT-767
ABT-767 monotherapy
Drug: ABT-767
ABT-767 once or twice daily for a 28 day cycle
Other Name: ABT-767

Detailed Description:

This is a Phase 1, dose escalation trial evaluating the tolerability, pharmacokinetics, and pharmacodynamics of ABT-767 in subjects with advanced BRCA1 or BRCA2-mutated solid tumors and high grade serous ovarian, fallopian tube, or primary peritoneal cancer. ABT-767 is a potent oral inhibitor of the enzymes poly (ADP-ribose) polymerase 1 and 2 (PARP-1 and PARP-2). Malignancies with deficiencies in homologous repair, such as BRCA-1 and BRCA-2 deficient tumors, are more dependent on PARP for deoxyribonucleic acid (DNA) repair than normal cells and, thus, are thought to be more sensitive to PARP inhibition. The study design is a single-arm dose escalation study to determine dose-limiting toxicities, maximum tolerated dose and the recommended Phase 2 dose (RPTD) of orally administered ABT-767 in subjects with BRCA mutations and malignancies. In order to further evaluate the safety and tolerability of ABT-767 at the RPTD, 20 additional subjects will be enrolled in an expanded safety cohort consisting of BRCA1- or BRCA2-mutated Breast cancer and Ovarian cancer.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Subject must be ≥ 18 years of age.
  2. Subjects must have histological or cytological confirmation of locally advanced or metastatic solid tumor, and a documented Breast Cancer Gene 1 or 2 mutation, or high grade serous ovarian, fallopian tube, or primary peritoneal cancer.
  3. Subject has an Eastern Cooperative Oncology Group (ECOG) Performance status of 0 to 2
  4. Subjects must have adequate hematologic, renal, and hepatic function as follows: a. Bone Marrow: Absolute neutrophil count (ANC ≥ 1,500/mm3 (1.5 ≥ 109/L); Platelets ≥ 100,000/mm3 (100 ≥ 109/L); Hemoglobin ≥ 9.0 g/dL (1.4 mmol/L) (hemoglobin unsupported by transfusion b. Subject has adequate renal function as demonstrated by serum creatinine value of ≤ 1.5 x the upper limit of normal (ULN) and either an estimated creatinine clearance value of ≥ 50 mL/min as determined by the Cockcroft-Gault formula or a creatinine clearance value of ≥ 50 mL/min/1.73 m2 based on a 24-hour urine collections c. Subject has adequate liver function as demonstrated by serum bilirubin ≤ 1.5 x ULN and Aspartate Aminotransferase (AST) and Alanine Transaminase (ALT) ≤ 2.5 ULN. For subjects with liver metastasis, AST and ALT < 5 x ULN. Partial Thromboplastin Time (PTT) must be ≤ ULN and INR < 1.5. - Subjects on anticoagulant (such as Coumadin) are allowed on study and will have PTT and International Normalize Ratio (INR) as determined by the Investigator.
  5. Women of childbearing potential must agree to use adequate contraception prior to study entry, for the duration of the study participation, and for 90 days following completion of therapy. Women of childbearing potential must have a negative serum pregnancy test within 21 days prior to initiation of treatment and a negative urine pregnancy test on the first day of study drug administration. Post-menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential.

Exclusion Criteria:

  1. Expanded cohort only: Subject has previously received a poly (ADP-ribose) polymerase (PARP) inhibitor.
  2. -Subject has received anti-cancer therapy including chemotherapy, immunotherapy, radiotherapy, biologic or any investigational therapy within a period of 28 days or 5 half lives (whichever is shorter) prior to Study Day 1.
  3. Subject has known Central Nervous System (CNS) metastases.
  4. Subject has unresolved toxicities from prior anti-cancer therapy, defined as any Common Terminology Criteria for Adverse Events (CTCAE v 4.0) grade 2 or higher clinically significant toxicity (excluding alopecia).
  5. Subject has had major surgery within 28 days prior to Study Day 1.
  6. Clinically significant uncontrolled condition(s) or any medical condition which in the opinion of the study investigator places the subject at an unacceptably high risk for toxicities.
  7. Psychiatric illness/social situation that would limit compliance with study requirements.
  8. Lactating or pregnant female.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01339650

Locations
Netherlands
Site Reference ID/Investigator# 44804
Groningn, Netherlands, 9713 GZ
Site Reference ID/Investigator# 44803
Nijmegen, Netherlands, 6525 GA
Site Reference ID/Investigator# 44802
Rotterdam, Netherlands, 3075 EA
Sponsors and Collaborators
AbbVie (prior sponsor, Abbott)
Investigators
Study Director: Stacie Shepherd, MD AbbVie
  More Information

No publications provided

Responsible Party: AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier: NCT01339650     History of Changes
Other Study ID Numbers: M10-976, 2010-020795-37
Study First Received: April 4, 2011
Last Updated: June 9, 2014
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by AbbVie:
Solid Tumor
BRCA 1 and BRCA 2 Mutations
Breast Cancer 1
Breast Cancer 2
High Grade Serous Ovarian, Fallopian Tube, or Primary Peritoneal Cancers
Solid Tumors

Additional relevant MeSH terms:
Breast Neoplasms
Peritoneal Neoplasms
Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Abdominal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Peritoneal Diseases

ClinicalTrials.gov processed this record on July 31, 2014