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

Phase 1
18 Years
Not Enrolling
Non-hematologic Malignancies, Metastatic Melanoma, Breast Cancer, Ovarian Cancer, Primary Peritoneal Cancer, Fallopian Tube Cancer, Hepatocellular Carcinoma

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Trial Information

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

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

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

- Anti-coagulant restrictions for subjects that have tumor biopsies.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum Tolerated Dose

Outcome Time Frame:

Duration of Study

Safety Issue:


Principal Investigator

Bhardwaj Desai, MD

Investigator Role:

Study Director

Investigator Affiliation:



United States: Food and Drug Administration

Study ID:




Start Date:

August 2007

Completion Date:

Related Keywords:

  • Non-hematologic Malignancies
  • Metastatic Melanoma
  • Breast Cancer
  • Ovarian Cancer
  • Primary Peritoneal Cancer
  • Fallopian Tube Cancer
  • Hepatocellular Carcinoma
  • Solid Tumor
  • Melanoma
  • Breast cancer
  • Ovarian cancer
  • Primary peritoneal cancer
  • Fallopian tube cancer
  • Hepatocellular carcinoma
  • HCC
  • BRCA deficient
  • BRCA mutation
  • Temozolomide
  • Temodar
  • TMZ
  • ABT-888
  • PARP inhibitor
  • Breast Neoplasms
  • Neoplasms
  • Carcinoma
  • Melanoma
  • Ovarian Neoplasms
  • Peritoneal Neoplasms
  • Fallopian Tube Neoplasms
  • Carcinoma, Hepatocellular



Site Ref # / Investigator 7571 Scottsdale, Arizona  85259
Site Ref # / Investigator 13321 Chicago, Illinois  60637
Site Ref # / Investigator 5239 Rochester, Minnesota  55905
Site Ref # / Investigator 18301 Philadelphia, Pennsylvania  19111