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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00526617
Recruitment Status : Completed
First Posted : September 10, 2007
Last Update Posted : November 21, 2017
Information provided by (Responsible Party):

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 Type : Interventional  (Clinical Trial)
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 : August 2007
Actual Primary Completion Date : June 2010

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

Primary Outcome Measures :
  1. Maximum Tolerated Dose [ Time Frame: Duration of Study ]
  2. Safety and Tolerability [ Time Frame: Duration of Study ]
  3. Pharmacokinetic Profile [ Time Frame: Duration of Study ]

Information from the National Library of Medicine

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

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00526617

Sponsors and Collaborators
Study Director: Bhardwaj Desai, MD Abbott

Publications of Results:
Responsible Party: AbbVie Identifier: NCT00526617     History of Changes
Other Study ID Numbers: M06-862
First Posted: September 10, 2007    Key Record Dates
Last Update Posted: November 21, 2017
Last Verified: January 2012

Keywords provided by AbbVie:
Solid Tumor
Breast cancer
Ovarian cancer
Primary peritoneal cancer
Fallopian tube cancer
Hepatocellular carcinoma
BRCA deficient
BRCA mutation
PARP inhibitor

Additional relevant MeSH terms:
Ovarian Neoplasms
Carcinoma, Hepatocellular
Fallopian Tube Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Endocrine Gland Neoplasms
Neoplasms by Site
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Neoplasms, Glandular and Epithelial
Liver Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Liver Diseases
Fallopian Tube Diseases