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(Peak) A Phase 3 Randomized Trial of CGT9486+Sunitinib vs. Sunitinib in Subjects With Gastrointestinal Stromal Tumors

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ClinicalTrials.gov Identifier: NCT05208047
Recruitment Status : Recruiting
First Posted : January 26, 2022
Last Update Posted : May 24, 2024
Sponsor:
Information provided by (Responsible Party):
Cogent Biosciences, Inc.

Tracking Information
First Submitted Date  ICMJE December 23, 2021
First Posted Date  ICMJE January 26, 2022
Last Update Posted Date May 24, 2024
Actual Study Start Date  ICMJE April 14, 2022
Estimated Primary Completion Date July 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 16, 2022)
  • Part 1a - pharmacokinetics - Cmax [ Time Frame: 16 days ]
    Maximum plasma concentration (Cmax)
  • Part 1a - pharmacokinetics - AUC [ Time Frame: 16 days ]
    Area under the plasma concentration-time curve (AUC)
  • Part 1b - pharmacokinetics - Cmax [ Time Frame: 14 days ]
    Maximum plasma concentration (Cmax)
  • Part 1b - pharmacokinetics - AUC [ Time Frame: 14 days ]
    Area under the plasma concentration-time curve (AUC)
  • Part 1b - pharmacokinetics - Tmax [ Time Frame: 14 days ]
    Time to maximum observed plasma concentration (Tmax)
  • Part 2 - Progression Free Survival (PFS) [ Time Frame: Approximately 48 months ]
    Time from first dose to documented disease progression or death due to any cause, whichever occurs first
Original Primary Outcome Measures  ICMJE
 (submitted: January 14, 2022)
  • Part 1a - pharmacokinetics - Cmax [ Time Frame: 16 days ]
    Maximum plasma concentration (Cmax)
  • Part 1a - pharmacokinetics - AUC [ Time Frame: 16 days ]
    Area under the plasma concentration-time curve (AUC)
  • Part 1b - pharmacokinetics - Cmax [ Time Frame: 14 days ]
    Maximum plasma concentration (Cmax)
  • Part 1b - pharmacokinetics - AUC [ Time Frame: 14 days ]
    Area under the plasma concentration-time curve (AUC)
  • Part 1b - pharmacokinetics - Tmax [ Time Frame: 14 days ]
    Time to maximum observed plasma concentration (Tmax)
  • Part 1b - pharmacokinetics - T1/2 [ Time Frame: 14 days ]
    Time to plasma concentration terminal half-life (T1/2)
  • Part 1b - pharmacokinetics - CLss/F [ Time Frame: 14 days ]
    Apparent total body clearance at steady state (CLss/F)
  • Part 2 - Progression Free Survival (PFS) [ Time Frame: Approximately 48 months ]
    Time from first dose to documented disease progression or death due to any cause, whichever occurs first
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 16, 2022)
  • All Study Parts - observing the safety of each treatment regimen. [ Time Frame: Approximately 48 months ]
    Incidence and severity of Adverse Events from first dose of study drug
  • All Study Parts - observing the safety of each treatment regimen. [ Time Frame: Approximately 48 months ]
    Incidence and severity of Serious Adverse Events from first dose of study drug
  • All Study Parts - observing the safety of each treatment regimen. [ Time Frame: Approximately 48 months ]
    Incidence of Adverse Events leading to dose modifications from first dose of study drug
  • All Study Parts - observing the safety of each treatment regimen. [ Time Frame: Approximately 48 months ]
    Change from baseline in laboratory results
  • All Study Parts - Overall Survival (OS) [ Time Frame: Approximately 48 months ]
    Time from first dose to death due to any cause
  • All Study Parts - Objective Response Rate (ORR) [ Time Frame: Approximately 48 months ]
    Percentage of subjects who achieved documented complete response (CR) + confirmed partial response (PR) based on modified Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
  • All Study Parts - Disease Control Rate (DCR) [ Time Frame: Approximately 48 months ]
    Percentage of subjects who achieved CR + PR + stable disease (SD) at 16 weeks
  • All Study Parts - Time to response (TTR) [ Time Frame: Approximately 48 months ]
    Time from first dose to first documented response based on modified Response Evaluation Criteria in Solid Tumors Version 1.1
  • All Study Parts - Duration of Response (DOR) [ Time Frame: Approximately 48 months ]
    Time from first response (CR or PR) to the date of progression or death from any cause, whichever occurs first
  • Part 2 Only - European Organisation for Research and Treatment of Cancer Quality of Life (EORTC-QLQ-30) [ Time Frame: Approximately 48 months ]
    Change in individual scores in patients with locally advanced, unresectable, or metastatic GIST treated with CGT9486 in combination with sunitinib compared with patients treated with sunitinib monotherapy. The scale comprises 30 questions, 24 of which are aggregated into 9 multi-item scales, to include 5 functioning scales (physical, role, cognitive, emotional and social), 3 symptom scales (fatigue, pain and nausea/vomiting) and 1 global health status scale. The remaining 6 single-item scales assess symptoms (dyspnea, appetite loss, sleep disturbance, constipation, diarrhea and the financial impact). All of the scales and single-item measures range in score from 0 to 100. Higher score for the functioning scales and global health status denote a better level of functioning, while higher scores on the symptom and single-item scales indicate a higher level of symptoms.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 14, 2022)
  • All Study Parts - observing the safety of each treatment regimen. [ Time Frame: Approximately 48 months ]
    Incidence and severity of Adverse Events from first dose of study drug
  • All Study Parts - observing the safety of each treatment regimen. [ Time Frame: Approximately 48 months ]
    Incidence and severity of Serious Adverse Events from first dose of study drug
  • All Study Parts - observing the safety of each treatment regimen. [ Time Frame: Approximately 48 months ]
    Incidence of Adverse Events leading to dose modifications from first dose of study drug
  • All Study Parts - observing the safety of each treatment regimen. [ Time Frame: Approximately 48 months ]
    Change from baseline in laboratory results
  • All Study Parts - Overall Survival (OS) [ Time Frame: Approximately 48 months ]
    Time from first dose to death due to any cause
  • All Study Parts - Objective Response Rate (ORR) [ Time Frame: Approximately 48 months ]
    Percentage of subjects who achieved documented complete response (CR) + confirmed partial response (PR) based on modified Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
  • All Study Parts - Disease Control Rate (DCR) [ Time Frame: Approximately 48 months ]
    Percentage of subjects who achieved CR + PR + stable disease (SD) at 16 weeks
  • All Study Parts - Time to response (TTR) [ Time Frame: Approximately 48 months ]
    Time from first dose to first documented response based on modified Response Evaluation Criteria in Solid Tumors Version 1.1
  • All Study Parts - Duration of Response (DOR) [ Time Frame: Approximately 48 months ]
    Time from first response (CR or PR) to the date of progression or death from any cause, whichever occurs first
  • All Study Parts - Evaluating the effect of each treatment regimen on pharmacodynamic biomarkers [ Time Frame: Approximately 48 months ]
    Mutations in KIT and PDGFR genes measured in plasma
  • All Study Parts - Evaluating the effect of each treatment regimen on pharmacodynamic biomarkers [ Time Frame: Approximately 48 months ]
    Determination of baseline genetic expression measured from peripheral blood to assess relationship with efficacy and safety outcomes
  • Part 2 Only - European Organisation for Research and Treatment of Cancer Quality of Life (EORTC-QLQ-30) [ Time Frame: Approximately 48 months ]
    Change in individual scores in patients with locally advanced, unresectable, or metastatic GIST treated with CGT9486 in combination with sunitinib compared with patients treated with sunitinib monotherapy. The scale comprises 30 questions, 24 of which are aggregated into 9 multi-item scales, to include 5 functioning scales (physical, role, cognitive, emotional and social), 3 symptom scales (fatigue, pain and nausea/vomiting) and 1 global health status scale. The remaining 6 single-item scales assess symptoms (dyspnea, appetite loss, sleep disturbance, constipation, diarrhea and the financial impact). All of the scales and single-item measures range in score from 0 to 100. Higher score for the functioning scales and global health status denote a better level of functioning, while higher scores on the symptom and single-item scales indicate a higher level of symptoms.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE (Peak) A Phase 3 Randomized Trial of CGT9486+Sunitinib vs. Sunitinib in Subjects With Gastrointestinal Stromal Tumors
Official Title  ICMJE A Phase 3 Randomized, Open-Label, Multicenter Clinical Study of CGT9486+Sunitinib vs. Sunitinib in Subjects With Locally Advanced, Unresectable, or Metastatic Gastrointestinal Stromal Tumors
Brief Summary This is a Phase 3, open-label, international, multicenter study of CGT9486 in combination with sunitinib. This is a multi-part study that will enroll approximately 426 patients. Part 1 consists of two evaluations: 1) confirming the dose of an updated formulation of CGT9486 to be used in subsequent parts in approximately 20 patients who have received at least one prior line of therapy for GIST and 2) evaluating for drug-drug interactions between CGT9486 and sunitinib in approximately 18 patients who have received at least two prior tyrosine kinase inhibitors (TKIs) for GISTs. The second part of the study will enroll approximately 388 patients who are intolerant to, or who failed prior treatment with imatinib only and will compare the efficacy of CGT9486 plus sunitinib to sunitinib alone with patients being randomized in a 1:1 manner.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
This is a multi-part study: Part 1a is a single-arm design, Part 1b is a two-arm parallel design drug-drug interaction evaluation in the first treatment cycle and single-arm design in subsequent treatment cycles, and Part 2 is a randomized two-arm parallel comparator study
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Advanced Gastrointestinal Stromal Tumors
  • Metastatic Cancer
Intervention  ICMJE
  • Drug: CGT9486 plus sunitinib
    Participants will receive both CGT9486 and sunitinib orally until study stopping rules are met.
  • Drug: CGT9486
    Participants will receive CGT9486 until steady state then both CGT9486 and sunitinib orally until study stopping rules are met.
  • Drug: Sunitinib
    Participants will receive sunitinib until steady state then both sunitinib and CGT9486 orally until study stopping rules are met.
    Other Name: sunitinib - Part 1b
  • Drug: Sunitinib
    Participants will receive sunitinib orally until study stopping rules are met.
    Other Name: sunitinib - Part 2
Study Arms  ICMJE
  • Experimental: Part 1a
    CGT9486 plus sunitinib 37.5 mg QD
    Intervention: Drug: CGT9486 plus sunitinib
  • Experimental: Part 2 - Experimental Group
    CGT9486 plus sunitinib 37.5 mg QD
    Intervention: Drug: CGT9486 plus sunitinib
  • Active Comparator: Part 2 - Control Group
    sunitinib 37.5 mg QD
    Intervention: Drug: Sunitinib
  • Experimental: Part 1b - DDI Cohort 1
    CGT9486 plus sunitinib 37.5 mg QD
    Intervention: Drug: CGT9486
  • Experimental: Part 1b - DDI Cohort 2
    sunitinib 37.5 mg QD plus CGT9486
    Intervention: Drug: Sunitinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 16, 2022)
426
Original Estimated Enrollment  ICMJE
 (submitted: January 14, 2022)
388
Estimated Study Completion Date  ICMJE September 2026
Estimated Primary Completion Date July 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria:

  1. Histologically confirmed locally advanced, metastatic, and/or unresectable GIST. Molecular pathology report must be available for Part 2; if molecular pathology report is unavailable or inadequate, an archival or fresh tumor tissue sample will be required to evaluate mutational status prior to randomization.
  2. Documented disease progression on or intolerance to imatinib
  3. Subjects must have received the following treatment:

    • Part 1a: Treatment with ≥1 prior lines of therapy for GIST
    • Part 1b: Treatment with ≥2 prior TKI for GISTs
    • Part 2: Prior treatment with imatinib only
  4. Have at least 1 measurable lesion according to mRECIST v1.1
  5. ECOG - 0 to 2
  6. Have clinically acceptable local laboratory screening results (clinical chemistry and hematology) within certain limits

Key Exclusion Criteria:

  1. Known PDGFR driving mutations or known succinate dehydrogenase deficiency
  2. Clinically significant cardiac disease
  3. Major surgeries (eg, abdominal laparotomy) within 4 weeks of the first dose of study drug
  4. Gastrointestinal abnormalities including, but not limited to, significant nausea and vomiting, malabsorption, external biliary shunt, or significant bowel resection that would preclude adequate absorption
  5. Any active bleeding excluding hemorrhoidal or gum bleeding
  6. Seropositive for HIV 1 or 2, or positive for hepatitis B surface antigen or hepatitis C virus (HCV) antibody.
  7. Active, uncontrolled, systemic bacterial, fungal, or viral infections at Screening
  8. Received strong CYP3A4 inhibitors or inducers
  9. Received sunitinib within 3 weeks (Part 1a, Part 1b)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Cogent Biosciences 617-945-5576 peakinfo@cogentbio.com
Listed Location Countries  ICMJE Argentina,   Australia,   Brazil,   Canada,   Chile,   Czechia,   Denmark,   France,   Germany,   Hong Kong,   Hungary,   Italy,   Korea, Republic of,   Mexico,   Netherlands,   Norway,   Poland,   Spain,   Sweden,   Taiwan,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05208047
Other Study ID Numbers  ICMJE CGT9486-21-301
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Cogent Biosciences, Inc.
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Cogent Biosciences, Inc.
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Jessica Sachs, MD Cogent Biosciences
PRS Account Cogent Biosciences, Inc.
Verification Date May 2024

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP