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

NCT01311713 | Terminated Phase 1 Results

• 2 other identifiers: C9722/20512010-023657-12
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Solid Tumors

Keywords

cancer; tumors; PARP

Outcome Measures

Primary Outcomes (2)

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

  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.

  Cycle 1 (28 days)

• Part 2: Number of Participants With Adverse Events

  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.

  Up to 8 months

Secondary Outcomes (5)

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

  Predose (0 hour), 0.5, 1, 2, 3, 4, 6, 8, and 12 hours postdose on Days 1 and 15 of Cycle 1

• 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)

  Predose (0 hour), 0.5, 1, 2, 3, 4, 6, 8, and 12 hours postdose on Days 1 and 15 of Cycle 1

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

  Predose (0 hour), 2 and 6 hours postdose on Days 1 and 15 of Cycle 1

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

  From the start of the treatment until disease progression/recurrence (up to 168 days)

• Part 2: Change in QT Interval

  Day 1 and Day 15, Cycle 1

Study Arms (7)

CEP-9722 Dose 1 QD

EXPERIMENTAL

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.

Drug: CEP-9722

CEP-9722 Dose 1 BID

EXPERIMENTAL

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.

Drug: CEP-9722

CEP-9722 Dose 2 BID

EXPERIMENTAL

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

Drug: CEP-9722

CEP-9722 Dose 3 BID

EXPERIMENTAL

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

Drug: CEP-9722

CEP-9722 Dose 4 BID

EXPERIMENTAL

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

Drug: CEP-9722

CEP-9722 Dose 5 BID

EXPERIMENTAL

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

Drug: CEP-9722

CEP-9722 Dose 6 BID

EXPERIMENTAL

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

Drug: CEP-9722

Interventions

CEP-9722 DRUG

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

Also known as: poly ADP ribose polymerase Inhibitor

CEP-9722 Dose 1 BID; CEP-9722 Dose 1 QD; CEP-9722 Dose 2 BID; CEP-9722 Dose 3 BID; CEP-9722 Dose 4 BID; CEP-9722 Dose 5 BID; CEP-9722 Dose 6 BID

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The participant has histologically confirmed, locally advanced or metastatic solid tumor considered incurable and unresponsive to standard therapies.
• The participant has disease progression following at least 1 prior standard chemotherapy regimen.
• The participant is a man or woman at least 18 years of age.
• The participant has a European Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
• The participant has a life expectancy of 12 weeks or more.
• The participant has adequate hematologic function as evidenced by:
• absolute neutrophil cell (ANC) count 1.5 x10\^9/liter (L) or more
• hemoglobin 10 grams (g)/deciliter (dL) or more
• platelets 100 x 10\^9/L or more
• The participant has adequate hepatic function as evidenced by:
• total bilirubin 1.5 times the upper limit of normal (ULN) or less, unless secondary to Gilbert's disease (any Gilbert's disease must be documented, and bilirubin must be 3 times the ULN or less.)
• alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase of 2.5 times ULN or less
• The participant has adequate renal function as defined by creatinine of less than 1.5 times ULN or less.
• The participant must take precautions to not become pregnant or produce offspring. Women must be of non-childbearing potential (surgically sterile or postmenopausal for at least 12 months, confirmed by follicle-stimulating hormone \[FSH\] \>40 IU/L) or agree to use a medically accepted method of contraception for the duration of the study and 90 days after treatment. Men must be surgically sterile or agree to use a medically accepted method of contraception for the duration of the study and 90 days after treatment. Acceptable methods of contraception include abstinence, barrier method with spermicide (excluding cervical cap and sponge), intrauterine device (IUD), or steroidal contraceptive (oral, transdermal, implanted, and injected) in conjunction with a barrier method.
• Written informed consent is obtained.

You may not qualify if:

• Other than malignancy, the participant has any serious or uncontrolled surgical, medical, or psychiatric history that could pose an unacceptable health risk to the participant, prevent compliance with study procedures, or compromise the study integrity, including, but not limited to the following:
• recent history of cardiac ischemic disease (acute myocardial infarction within 6 months, unstable angina)
• cardiac arrhythmia that is uncontrolled or that requires medication
• recent transient ischemic attack or stroke (within 6 months) or residual dysfunction from stroke
• history of seizure disorder (part 1 only)
• clinically significant pulmonary disease (eg, fibrosis on chest x-ray or significant dyspnea as assessed by investigator)
• poorly controlled hypertension (systolic \>140 millimeters of mercury (mm Hg) or diastolic \>90 mm Hg)
• uncontrolled active infection within the past 7 days
• poorly controlled diabetes mellitus as assessed by investigator
• recent major surgery (within 4 weeks prior to study day 1) or minor surgery (within 2 weeks prior to study day 1)
• The participant has previously received a PARP inhibitor.
• The participant has received antitumor therapy or other investigational agent within 4 weeks (with the exception of LHRH therapy in participants with prostate cancer) or nitrosourea therapy within 6 weeks.
• The participant has clinically symptomatic brain metastases or required treatment for brain metastases within 4 weeks (stable sequelae acceptable if treatment has been completed).
• The participant has residual adverse events of greater than grade 1 severity from prior radiotherapy or chemotherapy agents.
• The participant has known immunodeficiency virus (HIV) infection, acute or chronic hepatitis B infection,or hepatitis C infection.

Sponsors & Collaborators

• Teva Branded Pharmaceutical Products R&D, Inc.: lead

Study Sites (4)

Teva Investigational Site 1

Aurora, Colorado, 80045, United States

Location

Teva Investigational Site 3

Detroit, Michigan, 48202, United States

Location

Teva Investigational Site 4

St Louis, Missouri, 63110, United States

Location

Teva Investigational Site 2

Philadelphia, Pennsylvania, 19111, United States

Location

MeSH Terms

Conditions

Neoplasms

Interventions

CEP-9722; Poly(ADP-ribose) Polymerase Inhibitors

Intervention Hierarchy (Ancestors)

Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents; Therapeutic Uses

Limitations and Caveats

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.

Results Point of Contact

• Title: Director, Clinical Research
• Organization: Teva Branded Pharmaceutical Products R&D, Inc.

USMedInfo@tevapharm.com

1-888-483-8279

Study Officials

• Teva Medical Expert

  Teva Branded Pharmaceutical Products R&D, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 7, 2011
• First Posted: March 9, 2011
• Study Start: May 2, 2011
• Primary Completion: October 16, 2013
• Study Completion: October 16, 2013
• Last Updated: January 30, 2024
• Results First Posted: January 30, 2024

Record last verified: 2024-01

Locations

US (4)