Study of CEP-9722 as Single-Agent Therapy and as Combination Therapy With Temozolomide in Patients With Advanced Solid Tumors

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Teva Pharmaceutical Industries ( Cephalon )
ClinicalTrials.gov Identifier:
NCT00920595
First received: June 11, 2009
Last updated: August 14, 2012
Last verified: August 2012
  Purpose

An open-label study to evaluate the safety, pharmacokinetics, and pharmacodynamics of CEP-9722 as single-agent therapy and as combination therapy with temozolomide in patients with advanced solid tumors.


Condition Intervention Phase
Solid Tumor
Drug: CEP-9722
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Label Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of CEP-9722 (a PARP-1 and PARP-2 Inhibitor) as Single-Agent Therapy and as Combination Therapy With Temozolomide in Patients With Advanced Solid Tumors

Resource links provided by NLM:


Further study details as provided by Teva Pharmaceutical Industries:

Primary Outcome Measures:
  • Determination of Maximum Tolerated Dose (MTD) upon Dose Limiting Toxicities (DLT) data [ Time Frame: Up to 42 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Pharmacokinetic parameters [ Time Frame: Days 1 and 5 of Cycle 1 and on Day 5 of Cycle 2 ] [ Designated as safety issue: No ]
  • Pharmacodynamics assay [ Time Frame: Days 1, 5, and 8 of both Cycle 1 and Cycle 2 ] [ Designated as safety issue: No ]
  • Efficacy - will be assessed by the proportion of patients who achieve tumor response during the study [ Time Frame: A 14-day cycle and at least one 28-day cycle ] [ Designated as safety issue: No ]

Enrollment: 26
Study Start Date: June 2009
Study Completion Date: October 2011
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
CEP-9722 alone and in combination therapy with temozolomide.
Drug: CEP-9722
Starting dose of CEP-9722 is 150 mg/day (total dose). The study consists of a 14-day cycle of CEP-9722 alone, and at least one 28-day cycle of CEP-9722 plus temozolomide (150 mg/m2/day on Days 1-5). Patients who are receiving clinical benefit may receive subsequent cycles of study drug treatment.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • The patient has a histologically or cytologically confirmed malignant advanced solid tumor considered unresponsive or poorly responsive to accepted treatment modalities.
  • The patient has adequate hematologic assessments and adequate renal and hepatic functions as specified in the study protocol.
  • The patient has measurable or nonmeasurable disease documented with an appropriate method of evaluation according to disease characteristics.
  • The patient has had no chemotherapy for at least 3 weeks and has resolution of prior sequelae. If the patient has had prior curative radiation or prior treatment with nitrosoureas, a minimum of 4 weeks and 6 weeks, respectively, must have elapsed before treatment with CEP-9722.
  • The patient has had no immunotherapy, including monoclonal antibody therapy, for at least 4 weeks and no hormonotherapy for at least 1 week, with the exception of patients with prostate cancer, who may continue hormonal therapy.
  • The patient has a European Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
  • The patient has a life expectancy of 12 weeks or more.
  • Agreement by women of childbearing potential (not surgically sterile or 2 years postmenopausal) to use a medically accepted method of contraception and continue the use of this method for the duration of the study and for 90 days after participation in the study. Acceptable methods of contraception include abstinence, barrier method with spermicide, intrauterine device (IUD), or steroidal contraceptive (oral, transdermal, implanted, and injected) in conjunction with a barrier method.
  • Agreement by men not surgically sterile or who are capable of producing offspring to practice abstinence or use a barrier method of birth control, and continue use of this method for the duration of the study and for 6 months after participation in the study.

Exclusion Criteria:

  • The patient has a primary brain tumor whose disease requires a systematic premedication with anticonvulsive agents.
  • The patient has baseline cardiac abnormalities outside of the specified study parameters.
  • The patient has clinically symptomatic recurrent/progressive brain metastases within 4 weeks (stable sequelae are acceptable).
  • The patient has previous hypersensitivity reactions to 1 of the components of CEP-9722, temozolomide, or dacarbazine.
  • The patient is a pregnant or breast-feeding woman. (Any women becoming pregnant during the study will be withdrawn from the study.)
  • The patient is participating in another interventional clinical study at the time of enrollment, has participated in another interventional clinical study within 4 weeks prior to enrollment, or the patient has previously been already enrolled in this study.
  • The patient has an active gastroduodenal ulcer, uncontrolled high blood pressure, uncontrolled diabetes mellitus, or uncontrolled angina pectoris; has had a recent myocardial infarction; has had a cerebrovascular event within 6 months prior to study entry; or has pre-existing coagulopathy.
  • The patient has a concomitant uncontrolled infection or severe systemic disease.
  • The patient has a known nephropathy or hepatopathy.
  • The patient is receiving concurrent treatment with an antineoplastic agent other than temozolomide.
  • The patient has had previous treatment with another PARP inhibitor.
  • The patient is unable to swallow capsules.
  • The patient has taken any medications which are contraindicated as specified in the study protocol.
  • The patient has any serious or uncontrolled nonmalignant medical disorder or psychiatric disorder.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00920595

Locations
France
Cephalon Investigational Site
Nantes, France, 44805
United Kingdom
Cephalon Investigational Site
Newcastle upon Tyne, United Kingdom, NE7 7DN
Sponsors and Collaborators
Cephalon
Investigators
Study Director: Sponsor's Medical Expert, MD Cephalon France
  More Information

No publications provided

Responsible Party: Teva Pharmaceutical Industries ( Cephalon )
ClinicalTrials.gov Identifier: NCT00920595     History of Changes
Other Study ID Numbers: C9722/1065/PK/FR-UK, EudraCT number: 2008-006858-18
Study First Received: June 11, 2009
Last Updated: August 14, 2012
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Teva Pharmaceutical Industries:
Cancer

Additional relevant MeSH terms:
Neoplasms
Temozolomide
Alkylating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014