Veliparib Monotherapy for Relapsed Ovarian Cancer With BRCA Mutation (Veli-BRCA)

Veliparib (ABT888) Monotherapy for Patients With BRCA Germline Mutation and Platinum-Resistant or Partially Platinum-Sensitive Relapse of Epithelial Ovarian Cancer

The main purpose of this study is to investigate the effect of veliparib in ovarian cancer patients with known BRCA 1/2 mutations who do no longer respond to conventional chemotherapy.

Study Overview

• Status: Completed
• Conditions: Recurrent, Epithelial Ovarian Cancer
• Intervention / Treatment: Drug: Veliparib

Detailed Description

The side effects are modest, since PARP inhibitors affect cancer cells to a much larger extent than normal cells. The effect of this PARP-inhibiting treatment is evident although the greatest effect is seen in patients with mutations in BRCA genes. The reason for this is that BRCA deficient cancer cells are unable to repair both DNA double strand and single strand breaks and undergo apoptosis to a large extent.

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Denmark
  • Vejle, Denmark, 7100
    • Department of Oncology, Vejle Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Histologically confirmed epithelial, primary fallopian or primary peritoneal cancer. Stages I-IV.
2. Patients with known germline BRCA1/2 mutations
3. Verified progression by either RECIST criteria and/or GCIG CA125 criteria after previous first line chemotherapy or progression after later lines of cytotoxic treatment.
4. Platinum resistance or partially platinum sensitive disease (Relapsed within six months of prior first line/later lines of platinum-based therapy or relapsed within six to twelve months of prior first line/later lines of platinum-based therapy)
5. Age ≥ 18 years.
6. Performance status 0-2.
7. Measurable disease by RECIST 1.1 or evaluable by CA125 GCIG criteria

8. Adequate bone marrow function, liver function, renal function and coagulation parameters (within 7 days prior to randomization):

   WBC ≥ 3.0 x 10^9/l or neutrophils (ANC) ≥ 1.5 x 10^9/l Platelet count ≥ 100 x 10^9/l Hemoglobin ≥ 9.7 g/dl (6 mmol/L) Serum bilirubin ≤ 1.5 x ULN Serum transaminases ≤ 2.5 x ULN Serum creatinine ≤ 1.5 x ULN

9. Written informed consent.
10. Tissue available for BRCAness analysis.

Exclusion Criteria:

1. Previous treatment with a PARP inhibitor.
2. Platinum-refractory disease (disease that progressed or was stable during prior platinum therapy)
3. Patients who have received (or are planning to receive) treatment with any other investigational regimen, or who have participated in another clinical trial within 28 days prior to entering this trial.
4. Pregnant or breast-feeding patients. For fertile women a negative pregnancy test at screening is mandatory.
5. Fertile patients not willing to use acceptable and safe methods of contraception during and for 6 months after treatment

6. Other present or previous malignancy except curatively treated cervical cancer stage I, non-melanotic skin cancer or other cancer with minimal risk of relapse.

   Curatively treated prior breast cancer is allowed if no relapse is suspected at time of inclusion.

7. CNS metastasis.
8. History of any chronic medical or psychiatric condition or laboratory abnormality that is not medically controlled or in the opinion of the Investigator may increase the risks associated with study drug administration. (e.g. diabetes, cardiac diseases, hypertension, renal or liver disease).
9. Allergy to the ingredients of the study medication.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Veliparib	Drug: Veliparib; Veliparib (tablet) 300 mg twice daily on days 1-28 of 28 days cycles until progression, unacceptable toxicity or patient refusal.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Phase I: Maximum tolerated dose, dose limiting toxicity, recommended phase II dose.	6 months
Phase II: Response rate	Every 3 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall survival	Every 3 months
Progression free survival	Every 3 months

Collaborators and Investigators

• Sponsor: Vejle Hospital
• Collaborators: Abbott

Study record dates

Study Major Dates

• Study Start: November 1, 2011
• Primary Completion (ACTUAL): January 1, 2016
• Study Completion (ACTUAL): August 1, 2016

Study Registration Dates

• First Submitted: November 2, 2011
• First Submitted That Met QC Criteria: November 11, 2011
• First Posted (ESTIMATE): November 16, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): November 16, 2016
• Last Update Submitted That Met QC Criteria: November 15, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: PARP inhibitor; Ovarian cancer; BRCA1 mutation; BRCA2 mutation
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Poly(ADP-ribose) Polymerase Inhibitors; Veliparib
• Other Study ID Numbers: Veli-BRCA