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A Study of FT 2102 in Participants With Advanced Solid Tumors and Gliomas With an IDH1 Mutation

NCT03684811

Description:

This Phase 1/2 study will evaluate the safety, efficacy, PK, and PD of FT-2102 as a single agent and in combination with other anti-cancer drugs in patients with advanced solid tumors and gliomas. The study is divided into two parts: single agent FT-2102 followed by combination therapy. Part 1: A single agent, open-label study in up to five cohorts (glioma, hepatobiliary tumors, chondrosarcoma, intrahepatic cholangiocarcinoma, and other IDH1 mutant solid tumors) that will include a Phase 1 dose confirmation followed by a Phase 2 investigation of clinical activity in up to 4 cohorts. During the dose confirmation, additional doses or altered dose schedules may be explored. Part 2: An open-label study of FT-2102 in combination with other anti-cancer agents. Patients will be enrolled across 4 different disease cohorts, examining the effect of FT-2102 + azacitidine (glioma and chondrosarcoma), FT-2102+nivolumab (hepatobiliary tumors) and FT-2102+gemcitabine/cisplatin (intrahepatic cholangiocarcinoma). There will be a safety lead-in followed by a Phase 2 evaluation in up to four cohorts of patients.

Related Conditions:
  • Bile Duct Carcinoma
  • Chondrosarcoma
  • Glioma
  • Hepatocellular Carcinoma
  • Intrahepatic Cholangiocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of FT 2102 in Participants With Advanced Solid Tumors and Gliomas With an IDH1 Mutation
  • Official Title: A Phase 1b/2 Study of FT 2102 in Participants With Advanced Solid Tumors and Gliomas With an IDH1 Mutation

Clinical Trial IDs

  • ORG STUDY ID: 2102-ONC-102
  • NCT ID: NCT03684811

Conditions

  • Cohort 1a and 1b: Glioma
  • Cohort 1a and 1b: Glioblastoma Multiforme
  • Cohort 2a and 2b: Hepatobiliary Tumors (Hepatocellular Carcinoma, Bile Duct Carcinoma, Intrahepatic Cholangiocarcinoma, Other Hepatobiliary Carcinomas)
  • Cohort 3a and 3b: Chondrosarcoma
  • Cohort 4a and 4b: Intrahepatic Cholangiocarcinoma
  • Cohort 5a: Other Solid Tumors With IDH1 Mutations

Interventions

DrugSynonymsArms
FT-2102Phase 1b Dose Confirmation Single Agent (Cohorts 1a-5a)
AzacitidineVidazaPhase 1b and 2 Cohorts Combination (Cohorts 1b and 3b)
NivolumabOpdivoPhase 1b and 2 Cohort Combination (Cohort 2b)
Gemcitabine and CisplatinGemzar and PlatinolPhase 1b and 2 Cohort Combination (Cohort 4b)

Purpose

This Phase 1/2 study will evaluate the safety, efficacy, PK, and PD of FT-2102 as a single agent and in combination with other anti-cancer drugs in patients with advanced solid tumors and gliomas. The study is divided into two parts: single agent FT-2102 followed by combination therapy. Part 1: A single agent, open-label study in up to five cohorts (glioma, hepatobiliary tumors, chondrosarcoma, intrahepatic cholangiocarcinoma, and other IDH1 mutant solid tumors) that will include a Phase 1 dose confirmation followed by a Phase 2 investigation of clinical activity in up to 4 cohorts. During the dose confirmation, additional doses or altered dose schedules may be explored. Part 2: An open-label study of FT-2102 in combination with other anti-cancer agents. Patients will be enrolled across 4 different disease cohorts, examining the effect of FT-2102 + azacitidine (glioma and chondrosarcoma), FT-2102+nivolumab (hepatobiliary tumors) and FT-2102+gemcitabine/cisplatin (intrahepatic cholangiocarcinoma). There will be a safety lead-in followed by a Phase 2 evaluation in up to four cohorts of patients.

Trial Arms

NameTypeDescriptionInterventions
Phase 1b Dose Confirmation Single Agent (Cohorts 1a-5a)Experimental
  • FT-2102
Phase 2 Cohorts FT-2102 Single Agent (Cohorts 1a-5a)Experimental
  • FT-2102
Phase 1b and 2 Cohorts Combination (Cohorts 1b and 3b)Experimental
  • FT-2102
  • Azacitidine
Phase 1b and 2 Cohort Combination (Cohort 2b)Experimental
  • FT-2102
Phase 1b and 2 Cohort Combination (Cohort 4b)Experimental
  • FT-2102
  • Gemcitabine and Cisplatin

Eligibility Criteria

        Key Inclusion Criteria:

          -  Patients must have documented IDH1-R132 gene-mutated disease as evaluated by site

          -  Glioma: Advanced glioma that has recurred or progressed following standard therapy, or
             that has not responded to standard therapy.

          -  Hepatobiliary cancer that is relapsed/refractory or intolerant to approved
             standard-of-care therapy (included: hepatocellular carcinoma, bile duct carcinoma,
             intrahepatic cholangiocarcinoma or other hepatobiliary carcinomas)

          -  Chondrosarcoma that is relapsed or refractory and either locally advanced or
             metastatic and not amenable to complete surgical excision

          -  Intrahepatic cholangiocarcinoma that is advanced nonresectable or metastatic
             cholangiocarcinoma not eligible for curative resection or transplantation. Phase
             1b/Safety Lead-in of Phase 2: relapsed or refractory disease. Combination Phase 2
             (beyond Safety Lead-in): have received no more than 1 cycle of gemcitabine/cisplatin
             therapy

          -  Other solid tumors that have relapsed or refractory to standard-of-care therapy with
             no other available therapeutic options

          -  Good performance status

          -  Good kidney and liver function

        Key Exclusion Criteria:

          -  Prior solid organ or hematopoietic cell transplant

          -  Prior treatment with IDH1 inhibitor (Single agent cohorts only)

          -  Congestive heart failure (New York Heart Association Class III or IV) or unstable
             angina pectoris. Previous history of myocardial infarction within 1 year prior to
             study entry, uncontrolled hypertension or uncontrolled arrhythmias

          -  Unstable or severe, uncontrolled medical condition (e.g., unstable cardiac function,
             unstable pulmonary condition including pneumonitis and/or interstitial lung disease,
             uncontrolled diabetes)

          -  Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic
             therapy

          -  PD-1 only: active autoimmune disease
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of participants with a Dose Limiting Toxicity (DLT) [Phase 1]
Time Frame:within first 4 weeks of treatment
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Area under the plasma concentration versus time curve (AUC) [Phase 1 and Phase 2]
Time Frame:Blood samples for PK analysis collected at multiple visits during the first 60 days of treatment and on day 1 of all cycles (each cycle is 28 days) following the first 30 days
Safety Issue:
Description:
Measure:Peak Plasma Concentration (Cmax) [Phase 1 and Phase 2]
Time Frame:Blood samples for PK analysis collected at multiple visits during the first 60 days of treatment and on day 1 of all cycles (each cycle is 28 days) following the first 30 days
Safety Issue:
Description:
Measure:Time of peak plasma concentration Tmax [Phase 1 and Phase 2]
Time Frame:Blood samples for PK analysis collected at multiple visits during the first 60 days of treatment and on day 1 of all cycles (each cycle is 28 days) following the first 30 days
Safety Issue:
Description:
Measure:Time for half of the drug to be absent in blood stream following dose (T 1/2) [Phase 1 and Phase 2]
Time Frame:Blood samples for PK analysis collected at multiple visits during the first 60 days of treatment and on day 1 of all cycles (each cycle is 28 days) following the first 30 days
Safety Issue:
Description:
Measure:Rate at which drug is removed from blood stream (CL/F) [Phase 1 and Phase 2]
Time Frame:Blood samples for PK analysis collected at multiple visits during the first 60 days of treatment and on day 1 of all cycles (each cycle is 28 days) following the first 30 days
Safety Issue:
Description:
Measure:Rate of drug distribution within the blood stream (Vd/F) [Phase 1 and Phase 2]
Time Frame:Blood samples for PK analysis collected at multiple visits during the first 60 days of treatment and on day 1 of all cycles (each cycle is 28 days) following the first 30 days
Safety Issue:
Description:
Measure:Drug level within CSF (Glioma only) [Phase 1 and Phase 2]
Time Frame:CSF sample for drug concentration collected at day 1 of cycles 1 and 3 (each cycle is 28 days) and through study completion, up to 24 weeks, on average
Safety Issue:
Description:
Measure:Overall response rate of FT-2102 as a single-agent or in combination with azacitidine or nivolumab or gemcitabine/cisplatin [Phase 1]
Time Frame:Response Assessment Guidelines for solid tumors or gliomas respectively and based on investigator's assessment within 4 months
Safety Issue:
Description:
Measure:Incidence and severity of adverse events as assessed by CTCAE v4.0 as a single-agent or in combination with azacitidine or nivolumab or gemcitabine/cisplatin [Phase 1and 2]
Time Frame:Safety will be assessed from time of first dose through 28 days post last dose
Safety Issue:
Description:
Measure:Progression-Free Survival (PFS) [Phase 1b and 2]
Time Frame:From time of entry on study through progression, up to 24 weeks, on average
Safety Issue:
Description:
Measure:Time to Progression (TTP) [Phase 1b and 2]
Time Frame:From first dose of study drug through time of first response by blood recovery count, up to 24 weeks, on average
Safety Issue:
Description:
Measure:Duration of Response (DOR) [Phase 1b and 2]
Time Frame:From time of first response by blood recovery count through relapse, up to 24 weeks, on average
Safety Issue:
Description:
Measure:Overall Survival (OS) [Phase 1b and 2]
Time Frame:From time of entry on study through death or date last known alive at end of follow-up, up to 24 weeks, on average
Safety Issue:
Description:
Measure:Time to Response (TTR) [Phase 1b and 2]
Time Frame:From time of entry on study through death or date last known alive at end of follow-up, up to 24 weeks, on average
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Forma Therapeutics, Inc.

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