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Synovial SarcomaPhase 1NCT05355753

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

A Phase 1 study testing CFT8634 in people with Synovial Sarcoma and Soft Tissue Sarcoma, run by C4 Therapeutics, Inc. at 12 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

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… Read more about this study

Who is it for?
Ages 12 years and older
Conditions the study is for
Synovial Sarcoma, Soft Tissue Sarcoma
What is being tested?
CFT8634
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
49 participants
Where
12 sitesUnited States
Study dates
25 Mar 2022to 19 Dec 2023
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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
  • 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
  • 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
  • Subject must be:
  • ≥18 years of age (no minimum weight),
  • ≥16 and <18 years old and weighs ≥50 kg,
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  • ≥12 and <16 years of age and weighs ≥40kg,
  • or ≥16 and <18 years of age and weighs ≥40kg and <50kg
  • Subject must be able to safely swallow capsules
  • Subject must have measurable disease as defined by RECIST v1.1
  • Subject must have Eastern Cooperative Oncology Group performance status ≤2 or Lansky performance scale (LK scale) ≥ 60
  • Subject must have adequate organ function, defined as:
  • 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
  • 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)
  • 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
  • Renal function: must have a creatinine clearance ≥60 mL/min (via Cockcroft-Gault equation, institutional standard, or measured)
  • 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
  • Availability of archival tumor tissue sample or newly obtained core/excisional biopsy of a tumor not previously irradiated
  • 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
  • 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
  • A male subject must refrain from donating sperm while taking CFT8634 and for 90 days post-last dose
  • A female subject must refrain from donating ova while taking CFT8634 and for 180 days after discontinuation
  • All subjects must refrain from donating blood and blood products while receiving study drug and for 30 days post-last dose

Who cannot join

  • Subject has had major surgery within 21 days prior to the planned first dose of CFT8634
  • 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
  • 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
  • Subject has received radiation therapy within 14 days prior to the planned first dose of CFT8634
  • Prior treatment with BRD9 degrader
  • Subject has central nervous system (CNS) involvement (primary tumor or metastatic disease), except in the following circumstances:
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  • 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
  • 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
  • Subject has any evidence of a CNS bleed including intra-tumoral hemorrhage
  • Subject has known bleeding diathesis
  • 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)
  • Subject with presence of inflammatory vascular disease or microangiopathy (eg, thrombotic microangiopathies, hemolytic uremic syndrome [HUS], atypical HUS)
  • Subject with known malignancy, other than study indication, that is progressing or has required treatment within the past 3 years
  • 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
  • Subject has received live, attenuated vaccine within 28 days prior to first dose administration
  • Subject with known history of human immunodeficiency virus (HIV) infection
  • Subject had a venous thrombosis within 14 days prior to first dose of study drug
  • Subject with gastrointestinal absorption issues (e.g., malabsorption syndrome or other illness that could affect oral absorption).
  • Concurrent administration of strong cytochrome P450 (CYP) 3A4 inhibitors and inducers, and multidrug resistance mutation 1 (MDR1) inhibitors.

Trial locations and contacts

12 sites in 1 country.

12 sites in 1 country

United States12 sites
  • University of Colorado - Aurora Cancer Center

    Aurora, Colorado, 80045

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229

  • City of Hope

    Duarte, California, 91010

  • MD Anderson Cancer Center

    Houston, Texas, 77030

  • University of Iowa Hospital and Clinics

    Iowa City, Iowa, 52242

  • Mayo Clinic - Jacksonville

    Jacksonville, Florida, 32224

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

    New York, New York, 10021

  • Columbia University

    New York, New York, 10027

  • Mayo Clinic - Rochester

    Rochester, Minnesota, 55905

  • Sarcoma Oncology Research Center

    Santa Monica, California, 90403

  • Washington University School of Medicine

    St Louis, Missouri, 63110

Other trials in United States

About this study

Official title: A Phase 1/2 Open-Label, Multicenter Study to Characterize the Safety and Tolerability of CFT8634 in Subjects With Locally Advanced or Metastatic SMARCB1-Perturbed Cancers, Including Synovial Sarcoma and SMARCB1-Null Tumors

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.

Read the detailed description

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

Being tested
CFT8634
Keywords
Synovial Sarcoma, SMARB1-Null Tumors, CFT8634, Soft Tissue Sarcoma, Myoepithelial Carcinoma, Extraskeletal Myxoid Chondrosarcoma, Renal Medullary Carcinoma, Chordoma, Epithelioid Sarcoma
Medical subject headings
Sarcoma, Synovial, Sarcoma, Chondrosarcoma, Extraskeletal Myxoid, Chordoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CFT8634Drug

    Oral dose of CFT8634

Study groups in NCT05355753
Study groupRoleWhat they receive
Dose Escalation Phase 1/Part1: CFT8634ExperimentalUp 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
Receives: Drug: CFT8634
Dose Escalation Phase 1/Part 2: CFT8634ExperimentalUp 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
Receives: Drug: CFT8634
Phase 2 - Arm A: CFT8634ExperimentalApproximately 30 subjects with locally advanced or metastatic synovial sarcoma at the recommended phase 2 dose (RP2D) having received 1-2 prior anticancer therapies
Receives: Drug: CFT8634
Phase 2 - Arm B: CFT8634ExperimentalApproximately 20 subjects with locally advanced or metastatic SMARCB1-null tumors at the RP2D having received ≥1 prior anticancer therapy
Receives: Drug: CFT8634

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Frequency and severity of AEs and serious adverse events (SAEs)

    Phase 1 and Phase 2

    Measured: From screening until at least 30 days after completion of study treatment

  2. Number of subjects with changes between baseline and post-baseline safety assessments based on safety laboratory results graded by CTCAE v5.0

    Phase 1 and Phase 2

    Measured: From screening until at least 30 days after completion of study treatment

  3. Frequency of dose interruptions and dose reductions

    Phase 1 and Phase 2

    Measured: From first dose until end of treatment

  4. Incidence of dose limiting toxicities (DLTs)

    Phase 1 only

    Measured: From first dose until 28 days after first dose

  5. Overall Response Rate (ORR)

    Phase 2 only according to RECIST v1.1 criteria

    Measured: Up to approximately 24 months

Secondary outcomes (8)
  1. Plasma concentration of CFT8634 to characterize the pharmacokinetics (PK) parameters of CFT8634

    Plasma concentration of CFT8634 at the scheduled timepoints

    Measured: At multiple time points up to approximately 24 weeks

  2. Asses dose proportionality assessment

    Dose proportionately assessment at the scheduled timepoints

    Measured: At multiple time points up to approximately 24 weeks

  3. Assess the pharmacodynamics by percent reduction from baseline of target protein

    Tumor BRD9 degradation at scheduled timepoints

    Measured: At multiple time points up to approximately 24 weeks

  4. ORR

    Phase 1 only according to RECIST v1.1 criteria

    Measured: Up to approximately 24 months

  5. Duration of Response (DOR)

    DOR defined as time from first assessment of PR or CR to follow-on first assessment of progressive disease (PD)

    Measured: Up to approximately 24 months

  6. Progression Free Survival (PFS)

    PFS defined as the time from first treatment received until PD is assessed

    Measured: Up to approximately 24 months

  7. Overall Survival (OS)

    OS is defined as the time from first dose of study treatment to the date of death, irrespective of the cause of death. (Phase 2 only)

    Measured: Up to approximately 48 months

  8. Time to next treatment

    Interval from the date of initiation of a treatment to the date of commencement of the next line of therapy

    Measured: Up to approximately 8 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 May 2022
  2. Study start25 Mar 2022
  3. Primary completion19 Dec 2023
  4. Study completion19 Dec 2023

Why it stopped: High levels of BRD9 degradation did not result in sufficient efficacy in heavily pre-treated synovial sarcoma and SMARCB1-null solid tumor patients treated with CFT8634 as a single agent.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
49 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05355753
Sponsor's protocol ID
CFT8634-1101
Status last verified
Dec 2024
First submitted
23 Apr 2022
Last updated
17 Dec 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing CFT8634 in people with Synovial Sarcoma and Soft Tissue Sarcoma, run by C4 Therapeutics, Inc. at 12 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 17 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: High levels of BRD9 degradation did not result in sufficient efficacy in heavily pre-treated synovial sarcoma and SMARCB1-null solid tumor patients treated with CFT8634 as a single agent.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Frequency and severity of AEs and serious adverse events (SAEs) (time frame: From screening until at least 30 days after completion of study treatment). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Dec 2024.

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