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
Overview
- Phase
- Phase 1
- Intervention
- CEP-9722
- Conditions
- Solid Tumors or Mantle Cell Lymphoma
- Sponsor
- Cephalon
- Enrollment
- 24
- Locations
- 3
- Primary Endpoint
- 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.
- Status
- Completed
- Last Updated
- 13 years ago
Overview
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.
Investigators
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
- •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-
- •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.
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.
Arms & Interventions
CEP-9722 in combination with Gemcitabine and Cisplatin
Study drugs will be administered in cycles of 21 days for up to 6 cycles. CEP-9722 treatment will be initiated at cycle 2. After cycle 3, patients may discontinue gemcitabine and/or cisplatin for reasons of tolerability, at the discretion of the investigator.
Intervention: CEP-9722
CEP-9722 in combination with Gemcitabine and Cisplatin
Study drugs will be administered in cycles of 21 days for up to 6 cycles. CEP-9722 treatment will be initiated at cycle 2. After cycle 3, patients may discontinue gemcitabine and/or cisplatin for reasons of tolerability, at the discretion of the investigator.
Intervention: Gemcitabine
CEP-9722 in combination with Gemcitabine and Cisplatin
Study drugs will be administered in cycles of 21 days for up to 6 cycles. CEP-9722 treatment will be initiated at cycle 2. After cycle 3, patients may discontinue gemcitabine and/or cisplatin for reasons of tolerability, at the discretion of the investigator.
Intervention: Cisplatin
Outcomes
Primary Outcomes
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.
Time Frame: Baseline and endpoint (as soon as possible after Day 21 of the last cycle)
To determine the maximum tolerated dose of CEP-9722, as defined by dose-limiting toxicities (DLTs) reported during the second 21-day treatment cycle (the first cycle of CEP-9722 administration).
Secondary Outcomes
- Evaluate the safety and tolerability of CEP-9722 in combination with gemcitabine and cisplatin(During the entire study, a minimum of 6 wks (two 21-day cycles) up to a maximum of 18 wks (six 21-day cycles).)
- Cmax pharmacokinetics parameter(Days 2 and 7 of Cycle 2 and Day 7 of Cycle 3)
- AUC pharmacokinetics parameter(Days 2 and 7 of Cycle 2 and Day 7 of Cycle 3)
- Pharmacodynamics assessment(Screening and Day 2 of Cycle 2 at predose, and at 2 and 6 hours after administration of CEP-9722)
- Efficacy - will be assessed by Tumor response evaluation of each patient(Screening, cycles 3 and 6, and every 2 cycles after cycle 6 until disease progression)