Veliparib and Topotecan for Relapsed Ovarian Cancer With Negative or Unknown BRCA Status

Study Description

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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.

Condition or disease	Intervention/treatment	Phase
Ovarian Cancer	Drug: Veliparib; Drug: Topotecan	Phase 1; Phase 2

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	22 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
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 Start Date :	November 2012
Actual Primary Completion Date :	January 2015
Actual Study Completion Date :	February 2015

Arms and Interventions

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Arm	Intervention/treatment
Experimental: Veliparib and Topotecan	Drug: Veliparib; Veliparib (tablet) twice daily on days 1-3, 7-9, and 14-16 in a 28 days cycle. In phase I the starting dose is 30 mg x 2. Drug: Topotecan; 2 mg/m² iv over 30 minutes on days 2, 8, and 15 in cycles of 28 days. Topotecan is dosed at a maximum body surface area of 2 m².

Outcome Measures

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Primary Outcome Measures :

1. Phase I: Maximum tolerated dose, dose limiting toxicity and thus recommend phase II dose of veliparib [ Time Frame: 1 month ]
2. 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 [ Time Frame: Every three months, up to 3 years ]

Secondary Outcome Measures :

1. Progression free survival of ovarian cancer patients treated with topotecan and veliparib [ Time Frame: Every three months up to three years ]
2. Overall survival of ovarian cancer patients treated with topotecan and veliparib [ Time Frame: Every three months, up to three years ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	Female
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

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Locations

Denmark
Department of Oncology, Vejle Hospital
Vejle, Denmark, DK-7100

Sponsors and Collaborators

Vejle Hospital

Abbott

Investigators

Study Chair:	Anders Jakobsen, MD, DMSc	Vejle Hospital
Principal Investigator:	Hanne Kanstrup, MD	Vejle Hospital

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Vejle Hospital
ClinicalTrials.gov Identifier:	NCT01690598 History of Changes
Other Study ID Numbers:	VeTo
First Posted:	September 24, 2012
Last Update Posted:	June 10, 2015
Last Verified:	June 2015

Keywords provided by Vejle Hospital:

Epithelial ovarian cancer; BRCA mutation; Platinum resistant; Platinum sensitive; Relapsed ovarian cancer

Additional relevant MeSH terms:

Veliparib; Ovarian Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Genital Neoplasms, Female; Urogenital Neoplasms	Endocrine System Diseases; Gonadal Disorders; Topotecan; Topoisomerase I Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Poly(ADP-ribose) Polymerase Inhibitors