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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03684811




Registration number
NCT03684811
Ethics application status
Date submitted
17/09/2018
Date registered
26/09/2018
Date last updated
18/11/2023

Titles & IDs
Public title
A Study of FT-2102 in Patients With Advanced Solid Tumors and Gliomas With an IDH1 Mutation
Scientific title
A Phase 1b/2 Study of FT-2102 in Patients With Advanced Solid Tumors and Gliomas With an IDH1 Mutation
Secondary ID [1] 0 0
2102-ONC-102
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cohort 1a and 1b: Glioma (Advanced Gliomas and Glioblastoma Multiforme) 0 0
Cohort 2a and 2b: Hepatobiliary Tumors (Hepatocellular Carcinoma, Bile Duct Carcinoma, Intrahepatic Cholangiocarcinoma, Other Hepatobiliary Carcinomas) 0 0
Cohort 3a and 3b: Chondrosarcoma 0 0
Cohort 4a and 4b: Intrahepatic Cholangiocarcinoma 0 0
Cohort 5a: Other Non-Central Nervous System Solid Tumors With IDH1 Mutations 0 0
Condition category
Condition code
Cancer 0 0 0 0
Brain
Cancer 0 0 0 0
Biliary tree (gall bladder and bile duct)
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Cancer 0 0 0 0
Bone
Cancer 0 0 0 0
Sarcoma (also see 'Bone') - soft tissue

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - FT-2102
Treatment: Drugs - Azacitidine
Treatment: Other - Nivolumab
Treatment: Drugs - Gemcitabine and Cisplatin

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

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

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

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

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


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

Treatment: Drugs: Azacitidine
Azacitidine will be administered per the site's standard of care.

Treatment: Other: Nivolumab
Nivolumab will be administered per the site's standard of care.

Treatment: Drugs: Gemcitabine and Cisplatin
Gemcitabine and cisplatin will be administered per the site's standard of care.
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With a Dose Limiting Toxicity (DLT)
Timepoint [1] 0 0
Day 1-28
Primary outcome [2] 0 0
Overall Response Rate (ORR)
Timepoint [2] 0 0
While on treatment
Secondary outcome [1] 0 0
Area Under the Plasma Concentration Versus Time Curve (AUC)
Timepoint [1] 0 0
Cycles 1: Day 1 (0, 1, 2, 4, 8 hours post dose), Days 2, 8, 15, 22 pre dose. Cycles 2 Day 1 (0, 1, 2, 4, 8 hours post dose).
Secondary outcome [2] 0 0
Peak Plasma Concentration (Cmax)
Timepoint [2] 0 0
Cycles 1: Day 1 (0, 1, 2, 4, 8 hours post dose), Days 2, 8, 15, 22 pre dose. Cycles 2 Day 1 (0, 1, 2, 4, 8 hours post dose).
Secondary outcome [3] 0 0
Time of Peak Plasma Concentration (Tmax)
Timepoint [3] 0 0
Cycles 1: Day 1 (0, 1, 2, 4, 8 hours post dose), Days 2, 8, 15, 22 pre dose. Cycles 2 Day 1 (0, 1, 2, 4, 8 hours post dose).
Secondary outcome [4] 0 0
Time for Half of the Drug to be Absent in Blood Stream Following Dose (T 1/2)
Timepoint [4] 0 0
Cycles 1: Day 1 (0, 1, 2, 4, 8 hours post dose), Days 2, 8, 15, 22 pre dose. Cycles 2 Day 1 (0, 1, 2, 4, 8 hours post dose).
Secondary outcome [5] 0 0
Apparent Clearance (CL/F)
Timepoint [5] 0 0
Cycles 1: Day 1 (0, 1, 2, 4, 8 hours post dose), Days 2, 8, 15, 22 pre dose. Cycles 2 Day 1 (0, 1, 2, 4, 8 hours post dose).
Secondary outcome [6] 0 0
Rate of Drug Distribution Within the Blood Stream (Vd/F)
Timepoint [6] 0 0
Cycles 1: Day 1 (0, 1, 2, 4, 8 hours post dose), Days 2, 8, 15, 22 pre dose. Cycles 2 Day 1 (0, 1, 2, 4, 8 hours post dose).
Secondary outcome [7] 0 0
Olutasidenib Concentration Within Cerebro-spinal Fluid (CSF)
Timepoint [7] 0 0
CSF sample for drug concentration was collected at Day 1 of Cycles 1 and 3 (each cycle is 28 days) and through study completion, up to 24 weeks, on average.
Secondary outcome [8] 0 0
Progression-Free Survival (PFS)
Timepoint [8] 0 0
From time of entry on study through progression, up to 24 weeks, on average
Secondary outcome [9] 0 0
Time to Progression (TTP)
Timepoint [9] 0 0
From first dose of study drug through time of disease progression
Secondary outcome [10] 0 0
Duration of Response (DOR)
Timepoint [10] 0 0
From date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 44 weeks
Secondary outcome [11] 0 0
Overall Survival (OS)
Timepoint [11] 0 0
From date of first dose until the date of death from any cause, assessed up to 101 weeks
Secondary outcome [12] 0 0
Time to Response (TTR)
Timepoint [12] 0 0
Response may be observed from time of first dose through time of treatment discontinuation, up to 2 years.

Eligibility
Key inclusion criteria
Key

* 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 (including: 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
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, and uncontrolled diabetes)
* Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy
* PD-1 only: active autoimmune disease

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/11/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
13/06/2022
Sample size
Target
Accrual to date
Final
93
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Austin Hospital - Heidelberg
Recruitment hospital [2] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 0 0
3084 - Heidelberg
Recruitment postcode(s) [2] 0 0
VIC 3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Iowa
Country [6] 0 0
United States of America
State/province [6] 0 0
Massachusetts
Country [7] 0 0
United States of America
State/province [7] 0 0
Michigan
Country [8] 0 0
United States of America
State/province [8] 0 0
Missouri
Country [9] 0 0
United States of America
State/province [9] 0 0
New Jersey
Country [10] 0 0
United States of America
State/province [10] 0 0
New York
Country [11] 0 0
United States of America
State/province [11] 0 0
Texas
Country [12] 0 0
United States of America
State/province [12] 0 0
Utah
Country [13] 0 0
United States of America
State/province [13] 0 0
Wisconsin
Country [14] 0 0
France
State/province [14] 0 0
Bordeaux
Country [15] 0 0
France
State/province [15] 0 0
Lyon
Country [16] 0 0
France
State/province [16] 0 0
Marseille
Country [17] 0 0
France
State/province [17] 0 0
Villejuif
Country [18] 0 0
Korea, Republic of
State/province [18] 0 0
Seoul
Country [19] 0 0
Spain
State/province [19] 0 0
Barcelona
Country [20] 0 0
United Kingdom
State/province [20] 0 0
Glasgow
Country [21] 0 0
United Kingdom
State/province [21] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Forma Therapeutics, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT03684811
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Emma Barrett
Address 0 0
Forma Therapeutics
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT03684811