Clinical trial NCT01472783: Veliparib Monotherapy for Relapsed Ovarian Cancer With BRCA Mutation
Official title: Veliparib (ABT888) Monotherapy for Patients With BRCA Germline Mutation and Platinum-Resistant or Partially Platinum-Sensitive Relapse of Epithelial Ovarian Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Recurrent, Epithelial Ovarian Cancer
Keywords: BRCA1 mutation
BRCA2 mutation
Ovarian cancer
PARP inhibitor
Lead sponsor: Vejle Hospital
Sponsor class: OTHER
Collaborators: name: Abbott
First posted: 2011-11-16
Enrollment: 49
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Phase I: Maximum tolerated dose, dose limiting toxicity, recommended phase II dose.
timeFrame: 6 months
measure: Phase II: Response rate
timeFrame: Every 3 months
Secondary outcomes:
measure: Progression free survival
timeFrame: Every 3 months
measure: Overall survival
timeFrame: Every 3 months
Other outcomes:
Locations:
city: Vejle
country: Denmark
facility: Department of Oncology, Vejle Hospital
Study officials:
affiliation: Vejle Hospital, Vejle, Denmark
name: Anders Jakobsen, DMSc
role: STUDY_CHAIR
References: