Study of CEP-9722 in Combination With Gemcitabine and Cisplatin in Patients With Advanced Solid Tumors or Mantle Cell Lymphoma

• Register: ClinicalTrials.gov
• Last refreshed on: 19 February 2015
• Main ID: NCT01345357
• Date of registration: 19/04/2011
• Prospective Registration: Yes
• Primary sponsor: Cephalon
• Public title: Study of CEP-9722 in Combination With Gemcitabine and Cisplatin in Patients With Advanced Solid Tumors or Mantle Cell Lymphoma
• Scientific 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
• Date of first enrolment: May 2011
• Target sample size: 24
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT01345357
• Study type: Interventional
• Study design: Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
• Phase: Phase 1

Countries of recruitment

Belgium, France

Contacts

• Name: Sponsor's Medical Expert, MD
• Affiliation: Cephalon, France

Key inclusion & exclusion 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.



Age minimum: 18 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Solid Tumors or Mantle Cell Lymphoma

Intervention(s)

Drug: CEP-9722

Drug: Cisplatin

Drug: Gemcitabine

Primary Outcome(s)

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)]

Secondary Outcome(s)

Cmax pharmacokinetics parameter [Time Frame: Days 2 and 7 of Cycle 2 and Day 7 of Cycle 3]

Evaluate the safety and tolerability of CEP-9722 in combination with gemcitabine and cisplatin [Time Frame: During the entire study, a minimum of 6 wks (two 21-day cycles) up to a maximum of 18 wks (six 21-day cycles).]

Pharmacodynamics assessment [Time Frame: Screening and Day 2 of Cycle 2 at predose, and at 2 and 6 hours after administration of CEP-9722]

AUC pharmacokinetics parameter [Time Frame: Days 2 and 7 of Cycle 2 and Day 7 of Cycle 3]

Efficacy - will be assessed by Tumor response evaluation of each patient [Time Frame: Screening, cycles 3 and 6, and every 2 cycles after cycle 6 until disease progression]

Secondary ID(s)

2010-023658-36

C9722/1092

Source(s) of Monetary Support

Please refer to primary and secondary sponsors