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

November 17, 2017 updated by: AbbVie

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

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Enrollment (Actual)

41

Phase

  • Phase 1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Maximum Tolerated Dose
Time Frame: Duration of Study
Duration of Study
Safety and Tolerability
Time Frame: Duration of Study
Duration of Study
Pharmacokinetic Profile
Time Frame: Duration of Study
Duration of Study

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

AbbVie

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2007

Primary Completion (Actual)

June 1, 2010

Study Registration Dates

First Submitted

September 5, 2007

First Submitted That Met QC Criteria

September 5, 2007

First Posted (Estimate)

September 10, 2007

Study Record Updates

Last Update Posted (Actual)

November 21, 2017

Last Update Submitted That Met QC Criteria

November 17, 2017

Last Verified

January 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • M06-862

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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