Clinical Trial - NCT03684811

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

Recruiting

Sponsor: Forma Therapeutics, Inc.

Collaborators:

Information provided by (Responsible party): Sponsor

ClinicalTrials.gov Identifier: NCT03684811

Protocol Info

Short Description: Phase 1b/2 FT-2102 in Solid Tumors + Gliomas with an IDH1 Mutation
Long Description: A Phase 1b/2 Study of FT-2102 in Patients with Advanced Solid Tumors and Gliomas with an IDH1 Mutation
MGH Status: Open
Sponsor: FORMA Therapeutics, Inc.
Disease Program: Phase I

Next Steps


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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.
Condition Title Intervention Phase
Cohort 1a and 1b: Glioma Cohort 1a and 1b: Glioblastoma Multiforme Cohort 2a and 2b: Hepatobiliary Tumors (Hepatocellular Carcinoma, Bile Duct Carcinoma, Intrahepatic Cohort 3a and 3b: Chondrosarcoma Cohort 4a and 4b: Intrahepatic Cholangiocarcinoma Cohort 5a: Other Solid Tumors With IDH1 Mutations FT-2102 Azacitidine Nivolumab Gemcitabine and Cisplatin Phase 1/Phase 2
Study Type Interventional
Official Title A Phase 1b/2 Study of FT 2102 in Participants With Advanced Solid Tumors and Gliomas With an IDH1 Mutation

Primary Outcome Measures

Number of participants with a Dose Limiting Toxicity (DLT) [Phase 1] [Time Frame: within first 4 weeks of treatment] [Designated as safety issue: ]

Doses recommended for future studies [Phase 1] [Time Frame: Participants to be followed for duration of participation, an expected average of 16 weeks] [Designated as safety issue: ]

Objective response [CR+PR +MR (glioma only)] rate of FT-2102 single agent or in combination with azacitidine (glioma and chondrosarcoma), nivolumab (hepatobiliary tumors) and gemcitabine/cisplatin (intrahepatic cholangiocarcinoma) [Phase 2] [Time Frame: within 4 months of treatment] [Designated as safety issue: ]


Secondary Outcome Measures

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] [Designated as safety issue: ]

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] [Designated as safety issue: ]

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] [Designated as safety issue: ]

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] [Designated as safety issue: ]

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] [Designated as safety issue: ]

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] [Designated as safety issue: ]

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] [Designated as safety issue: ]

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] [Designated as safety issue: ]

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] [Designated as safety issue: ]

Progression-Free Survival (PFS) [Phase 1b and 2] [Time Frame: From time of entry on study through progression, up to 24 weeks, on average] [Designated as safety issue: ]

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] [Designated as safety issue: ]

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] [Designated as safety issue: ]

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] [Designated as safety issue: ]

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] [Designated as safety issue: ]

Estimated Enrollment: 200
Study Start Date: November 2018
Estimated Study Completion Date: April 2022
Estimated Primary Completion Date: September 2021
Arms Assigned Interventions

Experimental:Phase 1b Dose Confirmation Single Agent (Cohorts 1a-5a)

Drug:FT-2102
FT-2102 will be supplied as 150 mg capsule and will be administered per the protocol defined frequency and dose level.

Experimental:Phase 2 Cohorts FT-2102 Single Agent (Cohorts 1a-5a)

Experimental:Phase 1b and 2 Cohorts Combination (Cohorts 1b and 3b)

Drug:Azacitidine
Azacitidine will be administered per site's standard of care

Experimental:Phase 1b and 2 Cohort Combination (Cohort 2b)

Biological:Nivolumab
Nivolumab will be administered per site's standard of care

Experimental:Phase 1b and 2 Cohort Combination (Cohort 4b)

Drug:Gemcitabine and Cisplatin
Gemcitabine and Cisplatin will be administered per site's standard of care

Eligibility

Ages Eligible for Study: N/A-N/A

Genders Eligible for Study: All

Accepts Healthly Volunteers: No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT03684811

Locations

  • United States, California
    • City of Hope National Medical Center Duarte, California, United States, 91010
  • United States, Florida
    • University of Miami, Sylvester Comprehensive Cancer Center Miami, Florida, United States, 33136
  • United States, Iowa
    • Univerity of Iowa, Holden Comprehesive Cancer Institute Iowa City, Iowa, United States, 52242
  • United States, Massachusetts
    • Massachusetts General Hospital Boston, Massachusetts, United States, 02114
    • Dana Farber Cancer Institute Boston, Massachusetts, United States, 02215
  • United States, Michigan
    • Henry Ford Hospital Detroit, Michigan, United States, 48202
  • United States, Missouri
    • Washington University School of Medicine Saint Louis, Missouri, United States, 63110
  • United States, New Jersey
    • Rutgers Cancer Institute of New Jersey New Brunswick, New Jersey, United States, 08901
  • United States, New York
    • Columbia University Medical Center New York, New York, United States, 10032
  • United States, Texas
    • Baylor Scott and White Medical Center Temple, Texas, United States, 76508
  • United States, Utah
    • University of Utah, Huntsman Cancer Hospital Salt Lake City, Utah, United States, 84112
  • Australia,
    • Peter MacCallum Cancer Centre Melbourne, , Australia, VIC 3000
  • France,
    • Centre de Lutte Contre Cancre (CLCC) - Institute Bergonie Bordeaux, , France, 33076
  • United Kingdom,
    • The Royal Marsden Hospital London, , United Kingdom, SW3 6JJ

Sponsors and Collaborators

Forma Therapeutics, Inc.

More Information

No publications provided

Responsible Party: Sponsor
ClinicalTrials.gov Identifier: NCT03684811
Other Study ID Numbers:
Study First Received:
Last Updated:
Health Authority:

Additional relevant MeSH terms:

Neoplasms

Carcinoma, Hepatocellular

Glioblastoma

Glioma

Cholangiocarcinoma

Chondrosarcoma

Carcinoma, Ductal

Cisplatin

Gemcitabine

Nivolumab

Azacitidine

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.







ClinicalTrials.gov processed this data on May 30, 2019