Antineoplastic Agents

All Drugs and Chemicals

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

Participants will receive Dose 1 of CEP-9722 tablet once daily (QD) orally with a standard meal for up to 6 cycles of 28 days each.

Participants will receive Dose 1 of CEP-9722 tablets twice daily (BID) orally with a standard meal for up to 6 cycles of 28 days each.

Participants will receive Dose 2 of CEP-9722 tablets BID orally with a standard meal for up to 6 cycles of 28 days each.

Participants will receive Dose 3 of CEP-9722 tablets BID orally with a standard meal for up to 6 cycles of 28 days each.

Participants will receive Dose 4 of CEP-9722 tablets BID orally with a standard meal for up to 6 cycles of 28 days each.

Participants will receive Dose 5 of CEP-9722 tablets BID orally with a standard meal for up to 6 cycles of 28 days each.

Participants will receive Dose 6 of CEP-9722 tablets BID orally with a standard meal for up to 6 cycles of 28 days each.

CEP-9722 will be administered per dose and schedule specified in the arm description.

CEP-9722

Teva Medical Expert

CEP-9722 is an inhibitor of poly-adenosine diphosphate (ADP) ribose polymerase -1 and -2 (PARP). The primary purpose of this study is to (Part 1) determine the maximum tolerated dose (MTD) of CEP-9722 administered daily to participants with advanced or metastatic solid tumors, (Part 2) to evaluate the safety and tolerability of that dose, and to investigate whether CEP-9722 has antitumor activity as a single agent.

Study to Determine the Maximum Tolerated Dose of the PARP Inhibitor CEP-9722 in Participants With Solid Tumors

An Open-Label Study to Determine the Maximum Tolerated Dose of the PARP Inhibitor CEP-9722 When Administered as a Single Agent in Patients With Advanced or Metastatic Solid Tumors

MTD was defined as the highest dose level with 0 or 1 participant experiencing a dose-limiting toxicity (DLT) during cycle 1. DLT was defined as any adverse event (AE) that was considered by the investigator as related or potentially related to CEP-9722 as follows: 1) hematologic: grade 4 hematologic adverse events, grade 3 or greater febrile neutropenia, grade 3 thrombocytopenia lasting 7 days or more, grade 3 thrombocytopenia with bleeding; 2) nonhematologic: grade 3 or 4 nonhematologic AEs; grade 4 vomiting or diarrhea; grade 3 nausea, vomiting, or diarrhea that persisted for 48 hours or more despite optimal medical intervention; QTcF (QTc by Fridericia's cube root formula) greater than 500 milliseconds (msec) (confirmed by a repeat measurement on the same visit). During Cycle 1 of Part 1, any toxicity possibly related to treatment with CEP-9722 that caused a cumulative interruption of dosing for 7 or more days was considered dose limiting.

An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAEs were defined as death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.

ORR was assessed by the best tumor response (complete response \[CR\], partial response \[PR\], stable disease \[SD\], and progressive disease \[PD\]) during the study using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). CR: Disappearance of all target and non-target lesions. PR: At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started. PD: At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions and/or unequivocal progression of existing nontarget lesions.

Teva Branded Pharmaceutical Products R&D, Inc.

The safety analysis set included participants who received at least 1 dose of CEP-9722.

Participants received Dose 1 of CEP-9722 tablet QD orally with a standard meal for up to 6 cycles of 28 days each.

CEP-9722 Dose 1 QD

Participants received Dose 1 of CEP-9722 tablets BID orally with a standard meal for up to 6 cycles of 28 days each.

CEP-9722 Dose 1 BID

Participants received Dose 2 of CEP-9722 tablets BID orally with a standard meal for up to 6 cycles of 28 days each.

CEP-9722 Dose 2 BID

Participants received Dose 3 of CEP-9722 tablets BID orally with a standard meal for up to 6 cycles of 28 days each.

CEP-9722 Dose 3 BID

Participants received Dose 4 of CEP-9722 tablets BID orally with a standard meal for up to 6 cycles of 28 days each.

CEP-9722 Dose 4 BID

Participants received Dose 5 of CEP-9722 tablets BID orally with a standard meal for up to 6 cycles of 28 days each.

CEP-9722 Dose 5 BID

Participants received Dose 6 of CEP-9722 tablets BID orally with a standard meal for up to 6 cycles of 28 days each.

CEP-9722 Dose 6 BID

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race

Race/Ethnicity, Customized

The study was terminated due to the reasons which are related to the pharmaceutical properties of the compound and not related to any safety concerns.

Director, Clinical Research

Participants received CEP-9722 orally with a standard meal for up to 6 cycles of 28 days each.

Overall Population

The MTD determination set included all participants who received at least 1 dose of the study drug during the first cycle. In addition, any participant who experienced a drug related DLT during cycle 1 was considered evaluable regardless of the number of doses received.

Part 1: Maximum Tolerated Dose (MTD) of Oral CEP-9722

Part 2 of the study was not conducted, hence there were no analyses for any of the Part 2 outcome measures.

Part 2: Number of Participants With Adverse Events

Cycle 1 Day 1

Cycle 1 Day 15

The pharmacokinetic (PK) analysis set included participants for whom at least 1 PK parameter can be calculated. Here, 'number analyzed' = participants evaluable at specified timepoint.

Part 1: Maximum Observed Plasma Concentration (Cmax) of CEP-8983 (the Active Moiety of CEP-9722)

The PK analysis set included participants for whom at least 1 PK parameter can be calculated. Here, 'number analyzed' = participants evaluable at specified timepoint.

Part 1: Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Time of Last Measurable Drug Concentration (AUC0-t) of CEP-8983 (the Active Moiety of CEP-9722)

Pharmacodynamics was not evaluated in this study because the assay did not work due to sample collection methods.

Poly Adenosine Diphosphate-ribose (PAR) Concentration in Peripheral Blood Monocyte or Mononuclear Cells of CEP-8983 (the Active Moiety of CEP-9722)

Part 1: Overall Response Rate (ORR) - Percentage of Participants With the Best Tumor Response

Due to premature end of the study, Part 2 of the study was not conducted so there was no analysis of QT interval versus PK parameters.

Part 2: Change in QT Interval

Participants received Dose 1 of CEP-9722 tablet once daily (QD) orally with a standard meal for up to 6 cycles of 28 days each.

Participants received Dose 1 of CEP-9722 tablets twice daily (BID) orally with a standard meal for up to 6 cycles of 28 days each.

Spots Global Cancer Trial Database for Study to Determine the Maximum Tolerated Dose of the PARP Inhibitor CEP-9722 in Participants With Solid Tumors

Trial Identification

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Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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