Clinical trial NCT01690598: Veliparib and Topotecan for Relapsed Ovarian Cancer With Negative or Unknown BRCA Status
Official title: Veliparib (ABT888) and Topotecan (Hycamtin®) for Patients With Platinum-Resistant or Partially Platinum-Sensitive Relapse of Epithelial Ovarian Cancer With Negative or Unknown BRCA Status
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Ovarian Cancer
Keywords: Epithelial ovarian cancer
BRCA mutation
Platinum resistant
Platinum sensitive
Relapsed ovarian cancer
Lead sponsor: Vejle Hospital
Sponsor class: OTHER
Collaborators: name: Abbott
First posted: 2012-09-24
Enrollment: 22
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 purpose of this study is to investigate the effect of combined topotecan and veliparib (ABT888) treatment in relapsed ovarian cancer with tumor progression and negative or unknown BRCA mutation status.


Eligibility criteria: Inclusion Criteria:

1. Histologically confirmed epithelial, primary fallopian or primary peritoneal cancer.
2. Verified progression by either RECIST criteria and/or GCIG CA125 criteria after previous first line chemotherapy or progression after later lines of cytotoxic treatment.
3. 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-twelve months of prior first line/later lines of platinum-based therapy
4. Age ≥ 18 years.
5. Performance status 0-2.
6. Measurable disease by RECIST 1.1 or CA125 GCIG criteria
7. Adequate bone marrow function, liver function, renal function and coagulation parameters (within 7 days prior to enrollment):

   * WBC ≥ 3.0 x 10\^9/l or neutrophils (ANC) ≥ 1.5 x 10\^9/l
   * Platelet count ≥ 100 x 109/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
8. Written informed consent.
9. Tissue available for BRCAness analysis/BRCA mutation analysis.

Exclusion Criteria:

1. Prior treatment with a PARP inhibitor.
2. Patients with BRCA1/2 germline mutation.
3. Platinum-refractory disease (disease that progressed or was stable during prior platinum therapy)
4. Patients who have received (or are planning to receive) treatment with any other investigational agent, or who have participated in another clinical trial within 28 days prior to entering this trial.
5. Pregnant or breast-feeding. For fertile women a negative pregnancy test at screening is mandatory.
6. Fertile patients not willing to use acceptable and safe methods of contraception during and for 6 months after treatment
7. Other present or previous malignancy except curatively treated cervical cancer stage I, non-melanotic skin cancer or other cancer with minimal risk of relapse. Previous breast cancer is allowed, if disease free follow-up at least five years prior to enrollment.
8. CNS metastasis.
9. History of any chronic medical or psychiatric condition or laboratory abnormality, which 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).
10. Allergy to the ingredients of the study medication.

Primary outcomes:
measure: Phase I: Maximum tolerated dose, dose limiting toxicity and thus recommend phase II dose of veliparib
timeFrame: 1 month
measure: Phase II: To investigate response rates (based on either CA125 GCIG or RECIST criteria) of combination topotecan and veliparib (ABT888) in relapsed ovarian cancer with negative or unknown BRCA status
timeFrame: Every three months, up to 3 years
Secondary outcomes:
measure: Progression free survival of ovarian cancer patients treated with topotecan and veliparib
timeFrame: Every three months up to three years
measure: Overall survival of ovarian cancer patients treated with topotecan and veliparib
timeFrame: Every three months, up to three years
Other outcomes:
Locations:
city: Vejle
country: Denmark
facility: Department of Oncology, Vejle Hospital
Study officials:
affiliation: Vejle Hospital
name: Anders Jakobsen, MD, DMSc
role: STUDY_CHAIR
affiliation: Vejle Hospital
name: Hanne Kanstrup, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hjortkjaer M, Kanstrup H, Jakobsen A, Steffensen KD. Veliparib and topotecan for patients with platinum-resistant or partially platinum-sensitive relapse of epithelial ovarian cancer with BRCA negative or unknown BRCA status. Cancer Treat Res Commun. 2018;14:7-12. doi: 10.1016/j.ctarc.2017.09.001. Epub 2017 Sep 27. No abstract available.