Clinical trial NCT01345357: Study of CEP-9722 in Combination With Gemcitabine and Cisplatin in Patients With Advanced Solid Tumors or Mantle Cell Lymphoma
Official title: A Dose-Escalation Open-Label Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of CEP-9722 (a PARP 1 and PARP 2 Inhibitor) in Combination With Gemcitabine and Cisplatin in Patients With Advanced Solid Tumors or Mantle Cell Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumors or Mantle Cell Lymphoma
Keywords: Solid tumors
mantle cell lymphoma
Gemcitabine
Cisplatin
Cancer
Neoplasms
Antineoplastic agents
Lead sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
Sponsor class: INDUSTRY
First posted: 2011-05-02
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary objective of the study is to determine the maximum tolerated dose (MTD) of CEP-9722 in combination with gemcitabine and cisplatin in patients with advanced solid tumors or mantle cell lymphoma.


Eligibility criteria: Inclusion Criteria:

* Written informed consent is obtained. The patient has a either a histologically or cytologically confirmed malignant advanced solid tumor or a mantle cell lymphoma (and has experienced failure of as least 1 previous therapy) and the patient may benefit from the combination of gemcitabine and cisplatin.
* The patient has measurable or nonmeasurable disease evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 guidelines.
* The patient is a man or woman at least 18 years of age.
* The patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* The patient has a life expectancy of 12 weeks or more.
* The patient has adequate hematologic assessments and adequate renal and hepatic function as specified in the study protocol
* The patient has audiogram results without clinically significant abnormalities.
* The patient may have had chemotherapy provided that at least 3 weeks have elapsed and prior sequelae have resolved. If the patient has had prior radiation (curative or palliative) 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 hormonal therapy for at least 1 week, with the exception of patients with prostate cancer, who may continue hormonal therapy.
* Written informed consent is obtained.
* 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:

* With the exception of cancer, the patient has any serious or uncontrolled surgical, medical, or psychiatric history that could prevent compliance with study procedures, or compromise the integrity of the study.
* The patient has any of the protocol specified risk factors for Torsade de Pointes
* The patient has a brain lesion requiring systemic therapy with corticosteroids or anti-convulsive agents.
* The patient has previous hypersensitivity reactions to 1 or more of the components of the CEP-9722, gemcitabine, or cisplatin drug products.
* 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 or has participated in another interventional clinical study within 4 weeks prior to enrollment.
* The patient has any malabsorption syndrome and/or prior gastrectomy
* The patient has a concomitant uncontrolled and/or chronic infection or severe systemic disease.
* The patient has had previous treatment with another poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitor.
* The patient is unable to swallow tablets.
* The patient cannot interrupt continuous treatment with proton pump inhibitors and/or H2 receptor antagonists.

Primary outcomes:
measure: Determination of the maximum tolerated dose (MTD) of CEP-9722 in combination with gemcitabine and cisplatin in patients with advanced solid tumors or mantle cell lymphoma.
timeFrame: Baseline and endpoint (as soon as possible after Day 21 of the last cycle)
Secondary outcomes:
measure: Evaluate the safety and tolerability of CEP-9722 in combination with gemcitabine and cisplatin
timeFrame: During the entire study, a minimum of 6 wks (two 21-day cycles) up to a maximum of 18 wks (six 21-day cycles).
measure: Cmax pharmacokinetics parameter
timeFrame: Days 2 and 7 of Cycle 2 and Day 7 of Cycle 3
measure: AUC pharmacokinetics parameter
timeFrame: Days 2 and 7 of Cycle 2 and Day 7 of Cycle 3
measure: Pharmacodynamics assessment
timeFrame: Screening and Day 2 of Cycle 2 at predose, and at 2 and 6 hours after administration of CEP-9722
measure: Efficacy - will be assessed by Tumor response evaluation of each patient
timeFrame: Screening, cycles 3 and 6, and every 2 cycles after cycle 6 until disease progression
Other outcomes:
Locations:
city: Bruxelles
country: Belgium
facility: Teva Investigational Site 3
city: Nantes
country: France
facility: Teva Investigational Site 1
city: Villejuif
country: France
facility: Teva Investigational Site 2
Study officials:
affiliation: Cephalon, France
name: Sponsor's Medical Expert, MD
role: STUDY_DIRECTOR
References: