Trial Review

Did you know?

The ANZCTR now automatically displays published trial results and simplifies the addition of trial documents such as unpublished protocols and statistical analysis plans.

These enhancements will offer a more comprehensive view of trials, regardless of whether their results are positive, negative, or inconclusive.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
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