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

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ClinicalTrials.gov Identifier: NCT03684811
Recruitment Status : Recruiting
First Posted : September 26, 2018
Last Update Posted : May 1, 2019
Sponsor:
Information provided by (Responsible Party):
Forma Therapeutics, Inc.

Brief Summary:

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 or disease Intervention/treatment Phase
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 Drug: FT-2102 Drug: Azacitidine Biological: Nivolumab Drug: Gemcitabine and Cisplatin Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b/2 Study of FT 2102 in Participants With Advanced Solid Tumors and Gliomas With an IDH1 Mutation
Actual Study Start Date : November 1, 2018
Estimated Primary Completion Date : September 1, 2021
Estimated Study Completion Date : April 1, 2022


Arm Intervention/treatment
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) 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 1b and 2 Cohorts Combination (Cohorts 1b and 3b) Drug: FT-2102
FT-2102 will be supplied as 150 mg capsule and will be administered per the protocol defined frequency and dose level.

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

Experimental: Phase 1b and 2 Cohort Combination (Cohort 2b) Drug: FT-2102
FT-2102 will be supplied as 150 mg capsule and will be administered per the protocol defined frequency and dose level.

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

Experimental: Phase 1b and 2 Cohort Combination (Cohort 4b) Drug: FT-2102
FT-2102 will be supplied as 150 mg capsule and will be administered per the protocol defined frequency and dose level.

Drug: Gemcitabine and Cisplatin
Gemcitabine and Cisplatin will be administered per site's standard of care
Other Name: Gemzar and Platinol




Primary Outcome Measures :
  1. Number of participants with a Dose Limiting Toxicity (DLT) [Phase 1] [ Time Frame: within first 4 weeks of treatment ]
  2. Doses recommended for future studies [Phase 1] [ Time Frame: Participants to be followed for duration of participation, an expected average of 16 weeks ]
  3. 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 ]

Secondary Outcome Measures :
  1. 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 ]
  2. 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 ]
  3. 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 ]
  4. 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 ]
  5. 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 ]
  6. 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 ]
  7. 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 ]
  8. 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 ]
  9. 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 ]
  10. Progression-Free Survival (PFS) [Phase 1b and 2] [ Time Frame: From time of entry on study through progression, up to 24 weeks, on average ]
  11. 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 ]
  12. 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 ]
  13. 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 ]
  14. 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 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03684811


Contacts
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Contact: Kathryn Lipford 857-209-2242 klipford@formatherapeutics.com

Locations
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United States, California
City of Hope National Medical Center Recruiting
Duarte, California, United States, 91010
Contact: Mengsha Li       meli@coh.org   
United States, Florida
University of Miami, Sylvester Comprehensive Cancer Center Recruiting
Miami, Florida, United States, 33136
Contact: Tamara Leon    305-243-0865    txl351@med.miami.edu   
United States, Iowa
Univerity of Iowa, Holden Comprehesive Cancer Institute Recruiting
Iowa City, Iowa, United States, 52242
Contact: Heidi Haugland       heidi-haugland@uiowa.edu   
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Rachel Annese       rannese2@mgh.harvard.edu   
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Philip Chieng       Philip_Chieng@DFCI.HARVARD.EDU   
United States, Michigan
Henry Ford Hospital Recruiting
Detroit, Michigan, United States, 48202
Contact: John Gaggin       Jgaggin1@hfhs.org   
United States, Missouri
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Melissa Meredith       awl2132@cumc.columbia.edu   
Contact: Sarah Chandler       s.chandler@wustl.edu   
United States, New Jersey
Rutgers Cancer Institute of New Jersey Recruiting
New Brunswick, New Jersey, United States, 08901
Contact: Eileen Capstraw       emc252@cinj.rutgers.edu   
United States, New York
Columbia University Medical Center Recruiting
New York, New York, United States, 10032
Contact: Alex Liu       awl2132@cumc.columbia.edu   
United States, Texas
Baylor Scott and White Medical Center Recruiting
Temple, Texas, United States, 76508
Contact: Dedra Preece       Dedra.Preece@bswhealth.org   
United States, Utah
University of Utah, Huntsman Cancer Hospital Recruiting
Salt Lake City, Utah, United States, 84112
Contact: Matt Halverson       matt.halverson@hci.utah.edu   
Australia
Peter MacCallum Cancer Centre Recruiting
Melbourne, Australia, VIC 3000
Contact: Nathan Reader Wilson       Nathan.ReaderWilson@petermac.org   
France
Centre de Lutte Contre Cancre (CLCC) - Institute Bergonie Recruiting
Bordeaux, France, 33076
Contact: Mitchelle Rinaldo       M.Rinaldo@bordeaux.unicancer.fr   
United Kingdom
The Royal Marsden Hospital Recruiting
London, United Kingdom, SW3 6JJ
Contact: Stephanie Elston       Stephanie.Elston@rmh.nhs.uk   
Sponsors and Collaborators
Forma Therapeutics, Inc.
Investigators
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Study Director: Blythe Thomson, MD Forma Therapeutics

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Responsible Party: Forma Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT03684811     History of Changes
Other Study ID Numbers: 2102-ONC-102
First Posted: September 26, 2018    Key Record Dates
Last Update Posted: May 1, 2019
Last Verified: April 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Sarcoma
Carcinoma, Hepatocellular
Glioblastoma
Glioma
Cholangiocarcinoma
Chondrosarcoma
Carcinoma, Ductal
Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Astrocytoma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms, Ductal, Lobular, and Medullary
Gemcitabine
Cisplatin
Nivolumab
Azacitidine
Antineoplastic Agents