A Study of FORE8394 as a Single Agent in Patients With Advanced Unresectable Solid Tumors
|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 evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02428712|
Recruitment Status : Active, not recruiting
First Posted : April 29, 2015
Last Update Posted : March 27, 2023
- Study Details
- Tabular View
- No Results Posted
- How to Read a Study Record
|Condition or disease||Intervention/treatment||Phase|
|Advanced Unresectable Solid Tumors BRAF-mutated Tumors||Drug: FORE8394||Phase 1 Phase 2|
Dose Escalation (Part 1): To evaluate safety, pharmacokinetics, pharmacodynamics of FORE8394 in adult and pediatric patients with advanced BRAF- mutated tumors, and to identify the recommended Phase 2 Dose.
Dose Extension (Part 2): To access objective tumor response to FORE8394 treatment in adult and in adolescent patients with advanced BRAF- mutated tumors, to access RECIST, and to access pharmacokinetics, pharmacodynamics, and safety.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||113 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1/2a Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of FORE8394 in Patients With Advanced Unresectable Solid Tumors|
|Actual Study Start Date :||April 2015|
|Estimated Primary Completion Date :||February 2024|
|Estimated Study Completion Date :||April 2024|
Group A: Phase 1-Dose Escalation: Adult patients.
Group B: Phase 1-Dose Escalation: Pediatric patients.
Phase 2a-Dose Extension: Adult patients with advanced unresectable solid tumors will be enrolled among two cohorts.
Phase 2a-RP2D Confirmation: Adult patients.
Phase 2a-RP2D Redefinition and Extension:
Phase 2a-RP2D Redefinition:
- Area under the curve (AUC) of FORE8394 [ Time Frame: First dose of FORE8394 up to 30 days after end of treatment ]
- Maximum concentration (Cmax) of FORE8394 [ Time Frame: First dose of FORE8394 up to 30 days after end of treatment ]
- Time to peak concentration (Tmax) of FORE8394 [ Time Frame: First dose of FORE8394 up to 30 days after end of treatment ]
- Half life (T1/2) of FORE8394 [ Time Frame: First dose of FORE8394 up to 30 days after end of treatment ]
- Number of participants with Treatment Emergent Adverse Events (TEAEs) as assessed by CTCAE v4.0. [ Time Frame: First dose of FORE8394 up to 30 days after end of treatment ]
- To identify the recommended Phase 2 dose (RP2D) of FORE8394 in Group A (adult patients) for further evaluation in Dose Extension. [ Time Frame: 2 years ]
- Compare AUC of FORE8394 with FORE8394 [ Time Frame: First dose of FORE8394 up to 30 days after end of treatment ]
- Compare Cmax of FORE8394 with FORE8394 [ Time Frame: First dose of FORE8394 up to 30 days after end of treatment ]
- Compare Tmax of FORE8394 with FORE8394 [ Time Frame: First dose of FORE8394 up to 30 days after end of treatment ]
- Compare T1/2 of FORE8394 with FORE8394 [ Time Frame: First dose of FORE8394 up to 30 days after end of treatment ]
- To determine the overall response rate of FORE8394 treatment at the applicable RP2D in a) Group A, Cohort 1, and b) Group A, Cohort 2. [ Time Frame: 5 years ]
- To evaluate the duration of response (defined as time of initial response to progressive disease or death) at the applicable RP2D in Dose Extension. [ Time Frame: 5 years ]
- To evaluate the progression free survival (defined as time of first dose to progressive disease or death) at the applicable RP2D in Dose Extension. [ Time Frame: 5 years ]
- Clinical benefit rate (defined as stable disease, partial response and complete response) after 24 weeks on study [ Time Frame: 5 years ]
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
|Ages Eligible for Study:||10 Years and older (Child, Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
Inclusion Criteria- Group A:
- Age ≥ 10 years and at least 30 kg.
- Phase 1-Dose Escalation (no longer enrolling as of Protocol Amendment 10): Patients with histologically confirmed advanced solid tumors who are refractory to, relapsed after, or intolerant to standard therapy or for whom no standard therapy exists.
Phase 2a-Dose Extension: Criteria for Dose Extension [HME] Cohort 1 or Cohort 2, are specified below:
Phase 2a-Dose Extension-Cohort 1
- Patients with solid tumors (as of Amendment 10, only subjects with glioma tumors) driven by an activating BRAF-V600 mutation
- Patients with no prior exposure to BRAF-directed therapy and for whom no standard therapy exists.
Phase 2a-Dose Extension-Cohort 2
- Patients with solid tumors driven by an activating BRAF non-V600 mutation, which can include a point mutation, gene amplification, fusion, insertion, or deletion
- Participants with no prior exposure to BRAF-directed therapy and for whom no standard therapy exists.
Phase 2a - RP2D Redefinition Extension: Following RP2D redefinition, extension participants must meet criteria for Cohort 3 or Cohort 4 as specified below:
- Cohort 3: Participants with advanced unresectable gliomas driven by an activating BRAF V600 or activating non-V600 mutation who have no prior exposure to a BRAF, MEK, or ERK inhibitor and for whom no standard therapy exists.
- Cohorts 4-8: Participants with advanced solid tumors driven by activating BRAF non V600 mutations, which can include a point mutation, gene amplification, fusion, insertion, deletion, or alternative splicing, who have no prior exposure to a BRAF, MEK, or ERK inhibitor.
- Measurable disease by RECIST 1.1.
- RANOS (CNS tumors) - High Grade Glioma for high grade glioma (Grades 3 and 4) and RANO-Low Grade Glioma for low grade glioma.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
- Adequate hematologic, hepatic, and renal function.
- Women of child-bearing potential must have a negative pregnancy test and must agree to use an effective form of contraception from the time of the negative pregnancy test up to 3 months after the last dose of study drug. Women of non-child-bearing potential may be included if they are either surgically sterile or have been postmenopausal for ≥ 1 year.
- Fertile men must agree to use an effective method of birth control during the study and for up to 3 months after the last dose of study drug.
- Completion of previous anti-cancer therapy at least 2 weeks before study drug initiation.
Exclusion Criteria- Group A:
- Participants with known co-occurring RAS-related mutations or RTK activation are not allowed.
- Major surgical procedure, open biopsy (excluding skin cancer resection), or significant traumatic injury within 14 days of initiating study drug or anticipation of the need for major surgery during the study.
- Uncontrolled intercurrent illness.
- Patients with colorectal cancer or pancreatic cancer
- Active secondary malignancy unless the malignancy is not expected to interfere with the evaluation of safety and is approved by the Medical Monitor. Patients with a completely treated prior malignancy and no evidence of disease for ≥ 2 years are eligible.
- Refractory nausea and vomiting, malabsorption, external biliary shunt, or significant bowel resection that would preclude adequate absorption.
- Clinically significant cardiac disease.
- Known infection with HIV, HBV, or HCV or a known carrier of HBV or HCV.
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): NCT02428712
|United States, Arizona|
|Scottsdale, Arizona, United States, 85258|
|United States, California|
|St. Joseph's Hospital at Orange|
|Orange, California, United States, 92868|
|Stanford Hospitals and Clinics|
|Stanford, California, United States, 94305|
|United States, Florida|
|University of Miami|
|Miami, Florida, United States, 33136|
|United States, Indiana|
|Community Health Network|
|Indianapolis, Indiana, United States, 46011|
|United States, Massachusetts|
|Massachusetts General Hospital|
|Boston, Massachusetts, United States, 02114|
|United States, Michigan|
|Karmanos Cancer Institute|
|Detroit, Michigan, United States, 48201|
|United States, Missouri|
|Capital Regional Medical Center|
|Jefferson City, Missouri, United States, 65101|
|United States, New York|
|Memorial Sloan Kettering Cancer Center|
|New York, New York, United States, 10065|
|United States, Tennessee|
|Baptist Cancer Center|
|Memphis, Tennessee, United States, 38120|
|United States, Texas|
|MD Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Texas Children's Hospital (Baylor College of Medicine)|
|Houston, Texas, United States, 77030|
|United States, Utah|
|Huntsman Cancer Institute|
|Salt Lake City, Utah, United States, 84112|
|Study Chair:||Stacie Peacock Shepherd, MD, PhD||Fore Biotherapeutics U.S. Inc.|
|Responsible Party:||Fore Biotherapeutics|
|Other Study ID Numbers:||
|First Posted:||April 29, 2015 Key Record Dates|
|Last Update Posted:||March 27, 2023|
|Last Verified:||March 2023|