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Solid TumorsPhase 1/2NCT01311713

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

A Phase 1/2 study testing CEP-9722 in people with Solid Tumors, run by Teva Branded Pharmaceutical Products R&D, Inc. at 4 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Solid Tumors
What is being tested?
CEP-9722
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
45 participants
Where
4 sitesUnited States
Study dates
2 May 2011to 16 Oct 2013
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
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  • 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.
  • In Part 2: In addition to the criteria above, participants should have documented deficiencies of DNA repair pathways, such as BRCA1/2, or have prostate, breast, or gastric cancer and ability to provide fresh or archived tumor specimens.

Who cannot join

  • 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)
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  • 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.
  • The participant is a pregnant or breast-feeding woman. (Any women becoming pregnant during the study will be withdrawn from the study.)
  • The participant has medical or surgical gastrointestinal history that would interfere with the absorption of study drug.
  • The participant requires treatment with a proton pump inhibitor or H2 antagonist or has taken a proton pump inhibitor or H2 antagonist within 4 days before CEP-9722 administration.
  • The participant has risk factors for Torsades de Pointes as follows:
  • history of Long QT syndrome or unexplained syncope
  • history of congestive heart failure (New York Heart Association class III or IV)
  • concomitant treatment with medication known to prolong QT/QTc interval
  • QTc greater than 450 milliseconds (msec) at screening

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • Teva Investigational Site 1

    Aurora, Colorado, 80045

  • Teva Investigational Site 3

    Detroit, Michigan, 48202

  • Teva Investigational Site 2

    Philadelphia, Pennsylvania, 19111

  • Teva Investigational Site 4

    St Louis, Missouri, 63110

Other trials in United States

About this study

Official title: 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

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
Being tested
CEP-9722
Keywords
cancer, tumors, PARP
Medical subject headings
Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CEP-9722Drug

    Also called poly ADP ribose polymerase Inhibitor

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

Study groups in NCT01311713
Study groupRoleWhat they receive
CEP-9722 Dose 1 QDExperimentalParticipants 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.
Receives: Drug: CEP-9722
CEP-9722 Dose 1 BIDExperimentalParticipants 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.
Receives: Drug: CEP-9722
CEP-9722 Dose 2 BIDExperimentalParticipants will receive Dose 2 of CEP-9722 tablets BID orally with a standard meal for up to 6 cycles of 28 days each.
Receives: Drug: CEP-9722
CEP-9722 Dose 3 BIDExperimentalParticipants will receive Dose 3 of CEP-9722 tablets BID orally with a standard meal for up to 6 cycles of 28 days each.
Receives: Drug: CEP-9722
CEP-9722 Dose 4 BIDExperimentalParticipants will receive Dose 4 of CEP-9722 tablets BID orally with a standard meal for up to 6 cycles of 28 days each.
Receives: Drug: CEP-9722
CEP-9722 Dose 5 BIDExperimentalParticipants will receive Dose 5 of CEP-9722 tablets BID orally with a standard meal for up to 6 cycles of 28 days each.
Receives: Drug: CEP-9722
CEP-9722 Dose 6 BIDExperimentalParticipants will receive Dose 6 of CEP-9722 tablets BID orally with a standard meal for up to 6 cycles of 28 days each.
Receives: Drug: CEP-9722

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Cycle 1 (28 days)

  2. 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.

    Measured: Up to 8 months

Secondary outcomes (5)

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

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

  2. 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)

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

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

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

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

    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.

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

  5. Part 2: Change in QT Interval

    Measured: Day 1 and Day 15, Cycle 1

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Mar 2011 (estimated)
  2. Study start2 May 2011
  3. Primary completion16 Oct 2013
  4. Study completion16 Oct 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
45 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01311713
Sponsor's protocol ID
C9722/2051
Other IDs
2010-023657-12
Status last verified
Jan 2024
First submitted
7 Mar 2011
Last updated
30 Jan 2024
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing CEP-9722 in people with Solid Tumors, run by Teva Branded Pharmaceutical Products R&D, Inc. at 4 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 30 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 30 Jan 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part 1: Maximum Tolerated Dose (MTD) of Oral CEP-9722 (time frame: Cycle 1 (28 days)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01311713.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jan 2024.

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