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

NCT ID: NCT01339650

Last Updated: 2018-01-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 93 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-05-06
• Study Completion Date: 2017-11-30

Brief Summary

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.

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.

Conditions

Fallopian Tube; Primary Peritoneal Cancer; Solid Tumors (e.g. Breast, Ovarian, Prostate, or Pancreatic) and Ovarian

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

ABT-767

ABT-767 monotherapy

Group Type: EXPERIMENTAL

ABT-767

Intervention Type: DRUG

ABT-767 once or twice daily for a 28 day cycle

Interventions

ABT-767

ABT-767 once or twice daily for a 28 day cycle

Intervention Type: DRUG

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AbbVie (prior sponsor, Abbott)

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

AbbVie Inc.

Role: STUDY_DIRECTOR

AbbVie

Locations

Univ Med Center Groningen

Groningen, , Netherlands

Univ Med Ctr, St. Radboud

Nijmegen, , Netherlands

Erasmus Medisch Centrum

Rotterdam, , Netherlands

Countries

Netherlands

Other Identifiers

2010-020795-37

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

M10-976

Identifier Type: -

Identifier Source: org_study_id