Clinical Trial - NCT03684811

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

Active, not 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, Arizona
    • Banner MD Anderson Gilbert, Arizona, United States, 85234
  • United States, California
    • University of Southern California, Norris Comprehensive Cancer Center Los Angeles, California, United States, 90033
    • University of Southern California, Hoag Memorial Hospital Newport Beach, California, United States, 92663
  • United States, Colorado
    • University of Colorado Anschutz Medical Campus Aurora, Colorado, United States, 80045
  • United States, Florida
    • Mayo Clinic Jacksonville Jacksonville, Florida, United States, 32224
    • University of Miami, Sylvester Comprehensive Cancer Center Miami, Florida, United States, 33136
  • United States, Illinois
    • Northwestern University, Lurie Comprehensive Cancer Center Chicago, Illinois, United States, 60611
  • United States, Iowa
    • Univerity of Iowa, Holden Comprehesive Cancer Institute Iowa City, Iowa, United States, 52242
  • United States, Kansas
    • The University of Kansas Cancer Center Westwood, Kansas, United States, 66205
  • 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
    • Northwell Health Monter Cancer Center Lake Success, New York, United States, 11042
    • Columbia University Medical Center New York, New York, United States, 10032
  • United States, Ohio
    • The Ohio State University, Wexner Medical School Columbus, Ohio, United States, 43210
  • 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
  • United States, Wisconsin
    • Medical College of Wisconsin, Froedtert Hospital Milwaukee, Wisconsin, United States, 53226
  • Australia, Victoria
    • Austin Hospital Heidelberg, Victoria, Australia, 3084
  • Australia,
    • Peter MacCallum Cancer Centre Melbourne, , Australia, VIC 3000
  • France,
    • Centre de Lutte Contre Cancre (CLCC) - Institute Bergonie Bordeaux, , France, 33076
    • Hospital de la Timone Marseille, , France, 13385
    • Institut Gustave Roussy Cancer Campus Villejuif, , France, 94800
  • Korea, Republic of,
    • Seoul National University Hospital Seoul, , Korea, Republic of, 03080
    • Asan Medical Center Seoul, , Korea, Republic of, 05505
    • Samsung Medical Center Seoul, , Korea, Republic of, 06351
  • Spain,
    • Vall D'Hebron University Hospital Barcelona, , Spain, 08035
    • Instituto Catalan de Oncologia Barcelona, , Spain, 08916
    • START Madrid Madrid, , Spain, 28040
    • Hospital Universitario La Paz Madrid, , Spain, 28046
    • Hospital Universitario Virgen del Rocio Sevilla, , Spain, 41015
  • United Kingdom,
    • Cancer Research Beatson Institute Glasgow, , United Kingdom, G12 OYN
    • St. James Institute of Oncology Leeds, , United Kingdom, LS9 7BE
    • 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:

Glioblastoma

Glioma

Cholangiocarcinoma

Chondrosarcoma

Neoplasms

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 September 03, 2020