Clinical trial NCT03684811: A Study of FT-2102 in Patients With Advanced Solid Tumors and Gliomas With an IDH1 Mutation
Official title: A Phase 1b/2 Study of FT-2102 in Patients With Advanced Solid Tumors and Gliomas With an IDH1 Mutation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Cohort 1a and 1b: Glioma (Advanced Gliomas and 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 Non-Central Nervous System Solid Tumors With IDH1 Mutations
Keywords: Olutasidenib
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2018-09-26
Enrollment: 93
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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 (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 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

Primary outcomes:
measure: Number of Participants With a Dose Limiting Toxicity (DLT)
timeFrame: Day 1-28
measure: Overall Response Rate (ORR)
timeFrame: While on treatment
Secondary outcomes:
measure: Area Under the Plasma Concentration Versus Time Curve (AUC)
timeFrame: 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).
measure: Peak Plasma Concentration (Cmax)
timeFrame: 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).
measure: Time of Peak Plasma Concentration (Tmax)
timeFrame: 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).
measure: Time for Half of the Drug to be Absent in Blood Stream Following Dose (T 1/2)
timeFrame: 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).
measure: Apparent Clearance (CL/F)
timeFrame: 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).
measure: Rate of Drug Distribution Within the Blood Stream (Vd/F)
timeFrame: 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).
measure: Olutasidenib Concentration Within Cerebro-spinal Fluid (CSF)
timeFrame: 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.
measure: Progression-Free Survival (PFS)
timeFrame: From time of entry on study through progression, up to 24 weeks, on average
measure: Time to Progression (TTP)
timeFrame: From first dose of study drug through time of disease progression
measure: Duration of Response (DOR)
timeFrame: 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
measure: Overall Survival (OS)
timeFrame: From date of first dose until the date of death from any cause, assessed up to 101 weeks
measure: Time to Response (TTR)
timeFrame: Response may be observed from time of first dose through time of treatment discontinuation, up to 2 years.
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Banner MD Anderson
state: Arizona
city: Aurora
country: United States
facility: University of Colorado Anschutz Medical Campus
state: Colorado
city: Miami
country: United States
facility: University of Miami, Sylvester Comprehensive Cancer Center
state: Florida
city: Chicago
country: United States
facility: Northwestern University, Lurie Comprehensive Cancer Center
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa, Holden Comprehensive Cancer Institute
state: Iowa
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Temple
country: United States
facility: Baylor Scott and White Medical Center
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah, Huntsman Cancer Hospital
state: Utah
city: Milwaukee
country: United States
facility: Medical College of Wisconsin, Froedtert Hospital
state: Wisconsin
city: Heidelberg
country: Australia
facility: Austin Hospital
state: Victoria
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
city: Bordeaux
country: France
facility: Centre de Lutte Contre Cancer (CLCC) - Institute Bergonie
city: Lyon
country: France
facility: Centre de Lutte Cancre (CLCC) - Lyon
city: Marseille
country: France
facility: Hospital de la Timone
city: Villejuif
country: France
facility: Institut Gustave Roussy Cancer Campus
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Barcelona
country: Spain
facility: Vall D'Hebron University Hospital
city: Glasgow
country: United Kingdom
facility: Cancer Research Beatson Institute
city: London
country: United Kingdom
facility: The Royal Marsden Hospital
Study officials:
affiliation: Forma Therapeutics
name: Emma Barrett
role: STUDY_DIRECTOR
References: