A Phase I Study of ABT-888 in Combination With Temozolomide in Cancer Patients

Sponsor

AbbVie (Industry)

Overall Status

Completed

CT.gov ID

NCT00526617

Collaborator

(none)

Enrollment

Arm

Study Details

Study Description

Brief Summary

This Phase I clinical trial is studying the side effects and best dose of ABT-888 when given together with Temozolomide (chemotherapy) in treating patients with solid tumors, including metastatic melanoma (MM), BRCA deficient breast, ovarian, primary peritoneal, or fallopian tube cancer, and hepatocellular carcinoma (HCC).

Condition or Disease	Intervention/Treatment	Phase
Non-hematologic Malignancies Metastatic Melanoma Breast Cancer Ovarian Cancer Primary Peritoneal Cancer Fallopian Tube Cancer Hepatocellular Carcinoma	Drug: ABT-888 Drug: Temozolomide	Phase 1

Detailed Description

A Phase 1, multicenter, dose-escalation study evaluating the safety and tolerability of the PARP inhibitor ABT-888 in combination with Temozolomide (TMZ) in subjects with non-hematologic malignancies (NHM), including metastatic melanoma (MM), BRCA deficient breast, ovarian, primary peritoneal, or fallopian tube cancer, and hepatocellular carcinoma (HCC).

Study Design

Study Type:

Interventional

Actual Enrollment :

41 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase I Study of ABT-888 in Combination With Temozolomide (TMZ) in Subjects With Non-Hematologic Malignancies (NHM) and Metastatic Melanoma (MM)

Study Start Date :

Aug 1, 2007

Actual Primary Completion Date :

Jun 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Open Label Within each dose level, subjects are treated with the same regimen/doses of ABT-888 and TMZ.	Drug: ABT-888 Oral capsules Drug: Temozolomide Oral capsules Other Names: Temodar TMZ

Arm

Intervention/Treatment

Experimental: Open Label

Within each dose level, subjects are treated with the same regimen/doses of ABT-888 and TMZ.

Drug: ABT-888

Oral capsules

Drug: Temozolomide

Oral capsules

Other Names:

Temodar

TMZ

Outcome Measures

Primary Outcome Measures

Maximum Tolerated Dose [Duration of Study]
Safety and Tolerability [Duration of Study]
Pharmacokinetic Profile [Duration of Study]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Dose escalation and expanded safety cohorts

Evaluable disease, histologically confirmed malignancy (metastatic or unresectable) and standard curative measures or other therapy that may provide clinical benefit do not exist or are no longer effective
ECOG Performance Score less than or equal to 2
Adequate hematologic, renal and hepatic function
Normal sodium, calcium and magnesium levels
Voluntarily signed informed consent

Expanded Safety Cohorts Only

Population:
Metastatic melanoma (MM)
Hepatocellular carcinoma (HCC) Child Pugh Category A and B classification only
BRCA deficient tumor status*: advanced breast cancer (with soft tissue disease), or advanced ovarian cancer, or advanced primary peritoneal cancer, or advanced fallopian tube cancer*

*Patients must have histologically or cytologically confirmed solid tumors with a positive genetic test result documenting BRCA 1 or BRCA 2 mutation status, to be considered eligible.

Serial tumor biopsies: Required for all subjects enrolled in one of the Expanded Low Dose Safety Cohorts.

Exclusion Criteria:

Dose Escalation and Expanded Safety Cohorts

Known central nervous system (CNS) metastases or CNS primary cancer.
Previous or current malignancies at other sites, except: adequately treated in situ carcinoma of cervix uteri; basal/squamous cell carcinoma of skin; previous malignancy considered cured.
Previous history or current seizure disorder.
Clinically significant and uncontrolled major medical condition(s) or any medical condition that places the subject at an unacceptably high risk for toxicities.
Transplant recipients and patients receiving combination anti-retroviral therapy for HIV due to the use of immunosuppressant therapies.
Lactating or pregnant female.
Chemotherapy, immunotherapy, radiotherapy, biologic or any investigational therapy will not be allowed within either 4 weeks, or 5 half lives of a targeted therapy prior to study drug administration (Study Day 1).
Prior therapy with regimens containing dacarbazine (DTIC) or TMZ is not permitted.
Anti-cancer therapy is not permitted during the treatment portion of the study.
Hormone therapy, bisphosphonates or LHRH-agonists for prostate cancer are permitted prior to and during the study.
Significant adverse event or toxicity due to previous anti-cancer treatment that has not recovered to within one grade level (not to exceed Grade 2) of baseline.

Expanded Safety Cohorts Only:

MM Only: Prior treatment with DNA damaging agents or cytotoxic chemotherapy including carboplatin, cisplatin, fotemustine, paclitaxel, vincristine, TMZ and DTIC.
Prior therapy with biologic agents (including IL-2, interferon, bevacizumab, vaccines and immunostimulants) and signal transduction inhibitors (including sorafenib, erlotinib, sutent and elesclomol) are allowed.

Lower Dose Expanded Safety Cohorts Only