A Study to Assess the Safety and Tolerability of CFT8634 in Locally Advanced or Metastatic SMARCB1-Perturbed Cancers, Including Synovial Sarcoma and SMARCB1-Null Tumors

NCT ID: NCT05355753

Last Updated: 2024-12-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1

Total Enrollment

49 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-03-25

Study Completion Date

2023-12-19

Brief Summary

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This is an open-label, non-randomized, first-in-human Phase 1/2 study designed to evaluate the safety and tolerability of CFT8634 in subjects with synovial sarcoma and SMARCB1-null tumors who: have received prior systemic therapy; have relapsed/refractory tumors; have unresectable or metastatic disease; and are not candidates for available therapies known to confer clinical benefit. The study will characterize the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of CFT8634.

Detailed Description

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The study was intended to be Phase 1/2 trial but did not advance to Phase 2.

Conditions

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Synovial Sarcoma Soft Tissue Sarcoma

Keywords

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Synovial Sarcoma SMARB1-Null Tumors CFT8634 Soft Tissue Sarcoma Myoepithelial Carcinoma Extraskeletal Myxoid Chondrosarcoma Renal Medullary Carcinoma Chordoma Epithelioid Sarcoma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Dose Escalation Phase 1/Part1: CFT8634

Up to approximately 40 subjects ≥18 years of age or between ≥16 and \<18 years of age and weighing ≥50 kg with locally advanced or metastatic SMARCB1-perturbed cancers, including synovial sarcoma and SMARCB1-null tumors, having received ≥ 1 prior anticancer therapy

Group Type EXPERIMENTAL

CFT8634

Intervention Type DRUG

Oral dose of CFT8634

Dose Escalation Phase 1/Part 2: CFT8634

Up to approximately 6-12 subjects ≥12 and \<16 years of age and weighing ≥40 kg or ≥16 and \<18 years of age and weighing ≥40 kg and \<50 kg with locally advanced or metastatic SMARCB1-perturbed cancers, including synovial sarcoma and SMARCB1-null tumors

Group Type EXPERIMENTAL

CFT8634

Intervention Type DRUG

Oral dose of CFT8634

Phase 2 - Arm A: CFT8634

Approximately 30 subjects with locally advanced or metastatic synovial sarcoma at the recommended phase 2 dose (RP2D) having received 1-2 prior anticancer therapies

Group Type EXPERIMENTAL

CFT8634

Intervention Type DRUG

Oral dose of CFT8634

Phase 2 - Arm B: CFT8634

Approximately 20 subjects with locally advanced or metastatic SMARCB1-null tumors at the RP2D having received ≥1 prior anticancer therapy

Group Type EXPERIMENTAL

CFT8634

Intervention Type DRUG

Oral dose of CFT8634

Interventions

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CFT8634

Oral dose of CFT8634

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Subject (and legal guardian where applicable) is (are) willing and able to provide signed informed consent (or assent, where applicable) and can follow protocol requirements
2. Subject has histologically or cytologically confirmed synovial sarcoma or SMARCB1-null sold tumor that is relapsed/refractory, and unresectable or metastatic; the subject must not be a candidate for available therapies that are known to confer clinical benefit

a. Phase 1: subject must have received ≥1 prior line of systemic anticancer therapy considered to be Standard of Care per the Investigator's judgment, in the metastatic or unresectable setting b. Phase 2: i. Arm A: subject must have received only 1-2 prior lines of systemic anticancer therapy considered to be Standard of Care per the Investigator's judgment, in the metastatic or unresectable setting ii. Arm B: subject must have received ≥1 prior line of systemic anticancer therapy considered to be Standard of Care per the Investigator's judgment, in the metastatic or unresectable setting
3. Subject must be:

* ≥18 years of age (no minimum weight),
* ≥16 and \<18 years old and weighs ≥50 kg,
* ≥12 and \<16 years of age and weighs ≥40kg,
* or ≥16 and \<18 years of age and weighs ≥40kg and \<50kg
4. Subject must be able to safely swallow capsules
5. Subject must have measurable disease as defined by RECIST v1.1
6. Subject must have Eastern Cooperative Oncology Group performance status ≤2 or Lansky performance scale (LK scale) ≥ 60
7. Subject must have adequate organ function, defined as:

1. Bone marrow function: absolute neutrophil count ≥1.0 x 109/L independent of growth factor support for ≤7 days prior to first dose of study drug for granulocyte colony-stimulating factor and ≤14 days prior to first dose of study drug for peg-filgrastim; hemoglobin ≥8 g/dL independent of transfusion support for ≤7 days prior to first dose of study drug; platelet count ≥75 x 109 /L independent of transfusion support for ≤3 days prior to first dose of study drug
2. Coagulation: Prothrombin time (PT)/international normalized ratio (INR) \<1.5x the upper limit of normal (ULN) and activated partial thromboplastin time (aPTT) \<1.5x ULN (unless the subject is receiving anticoagulant therapy and INR and partial PT/aPTT are within therapeutic range of intended use of anticoagulants)
3. Liver function: total bilirubin ≤1.5x ULN (≤3.0x ULN for subjects with Gilbert's syndrome), aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3.0x ULN; except for subjects who have tumor infiltration of the liver, where ALT and AST ≤5x ULN
4. Renal function: must have a creatinine clearance ≥60 mL/min (via Cockcroft-Gault equation, institutional standard, or measured)
5. Cardiac function: baseline corrected QT interval using Fredericia's formula ≤470 ms (adolescents 12-17 years of age: ≤450 ms) and a left ventricular ejection fraction ≥50% evaluated via echocardiogram or multi-gated acquisition (MUGA) scan
8. Availability of archival tumor tissue sample or newly obtained core/excisional biopsy of a tumor not previously irradiated
9. A female subject may be eligible to participate if she is not pregnant or planning a pregnancy, not breastfeeding, and following protocol mediated guidance to avoid pregnancy
10. A male subject must have had a prior vasectomy and agree to use a condom during the treatment period and for at least 90 days after the last dose of study treatment
11. A male subject must refrain from donating sperm while taking CFT8634 and for 90 days post-last dose
12. A female subject must refrain from donating ova while taking CFT8634 and for 180 days after discontinuation
13. All subjects must refrain from donating blood and blood products while receiving study drug and for 30 days post-last dose

Exclusion Criteria

1. Subject has had major surgery within 21 days prior to the planned first dose of CFT8634

a. Minor surgery (eg, minor biopsy of extracranial site, central venous catheter placement, shunt revision) is permitted within 21 days prior to first dose of CFT8634
2. Subject has received standard of care or investigational systemic anti-neoplastic therapy within 14 days or 5 half-lives, whichever is shorter, prior to the planned first dose of CFT8634
3. Subject has received radiation therapy within 14 days prior to the planned first dose of CFT8634
4. Prior treatment with BRD9 degrader
5. Subject has central nervous system (CNS) involvement (primary tumor or metastatic disease), except in the following circumstances:

1. Subjects with previously treated brain metastases may be permitted to participate provided they are stable (without evidence of progression by imaging 14 days prior to the first dose of study drug and any neurologic symptoms have stabilized), have no evidence of new or enlarging brain metastases, and if they are taking corticosteroids, they are on stable or tapering doses for at least 7 days prior to first dose of study drug. Antiseizure therapy is permitted provided the medication is not otherwise excluded and seizures have been controlled for at least 28 days since the last antiseizure medication adjustment
2. Subjects with asymptomatic brain metastases found on Screening magnetic resonance imaging (MRI) may be permitted to be entered into the study without prior radiation therapy to the brain if they do not require immediate surgical or radiation therapy in the opinion of the treating investigator and in the opinion of a radiation therapy or neurosurgical consultant
6. Subject has any evidence of a CNS bleed including intra-tumoral hemorrhage
7. Subject has known bleeding diathesis
8. Subject has impaired cardiac function or clinically significant cardiac disease (i.e. uncontrolled heart disease/hypertension, clinically significant arrythmias, unstable angina/myocardia infarction/stroke within 180 days prior to screening)
9. Subject with presence of inflammatory vascular disease or microangiopathy (eg, thrombotic microangiopathies, hemolytic uremic syndrome \[HUS\], atypical HUS)
10. Subject with known malignancy, other than study indication, that is progressing or has required treatment within the past 3 years

a. Subject with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (i.e. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded
11. Subject has received live, attenuated vaccine within 28 days prior to first dose administration
12. Subject with known history of human immunodeficiency virus (HIV) infection
13. Subject had a venous thrombosis within 14 days prior to first dose of study drug
14. Subject with gastrointestinal absorption issues (e.g., malabsorption syndrome or other illness that could affect oral absorption).
15. Concurrent administration of strong cytochrome P450 (CYP) 3A4 inhibitors and inducers, and multidrug resistance mutation 1 (MDR1) inhibitors.
Minimum Eligible Age

12 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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C4 Therapeutics, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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City of Hope

Duarte, California, United States

Site Status

Sarcoma Oncology Research Center

Santa Monica, California, United States

Site Status

University of Colorado - Aurora Cancer Center

Aurora, Colorado, United States

Site Status

Mayo Clinic - Jacksonville

Jacksonville, Florida, United States

Site Status

University of Iowa Hospital and Clinics

Iowa City, Iowa, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Mayo Clinic - Rochester

Rochester, Minnesota, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

Columbia University

New York, New York, United States

Site Status

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Site Status

MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Countries

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United States

Other Identifiers

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CFT8634-1101

Identifier Type: -

Identifier Source: org_study_id