Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Rare Diseases

Carcinoma

Sarcoma

Chondrosarcoma

Carcinoma, Medullary

Sarcoma, Synovial

Chordoma

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Neoplasms, Connective Tissue

Soft Tissue Sarcoma

Thyroid Cancer, Medullary

Renal Medullary Carcinoma

Synovial Sarcoma

Epithelioid Sarcoma

Myoepithelial Carcinoma

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

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

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

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

CFT8634

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.

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 1/2 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

Phase 2 only according to RECIST v1.1 criteria

Plasma concentration of CFT8634 at the scheduled timepoints

Dose proportionately assessment at the scheduled timepoints

Tumor BRD9 degradation at scheduled timepoints

Phase 1 only according to RECIST v1.1 criteria

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

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

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)

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

C4 Therapeutics, Inc.

Mouth and Tooth Diseases

Nervous System Diseases

Carcinoma, Squamous Cell

Melanoma

Salivary Gland Neoplasms

Carcinoma, Adenoid Cystic

Esthesioneuroblastoma, Olfactory

Carcinoma, Mucoepidermoid

Mucoepidermoid Tumor

Neoplasms, Glandular and Epithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Adenocarcinoma

Neoplasms, Cystic, Mucinous, and Serous

Neuroblastoma

Neuroectodermal Tumors, Primitive, Peripheral

Neoplasms, Neuroepithelial

Olfactory Nerve Diseases

Cranial Nerve Diseases

Adenoid Cystic Carcinoma

Olfactory Neuroblastoma

Sinonasal Undifferentiated Carcinoma

Mucoepidermoid Carcinoma

Neuroepithelioma

Subjects treated at Massachusetts General Hospital with proton beam therapy

Intensity-modulated radiation therapy at institutions other than Massachusetts General Hospital

Proton radiation therapy

Intensity-modulated radiotherapy

Annie W Chan, MD

The purpose of this study is to test the hypothesis that 1)intensity-modulated radiotherapy (IMRT) or proton radiation therapy would result in improved local control rate and lowered toxicity compared to conventional radiotherapy, and 2) proton radiation therapy would result in equivalent or improved local control rate with similar or lower toxicity compared to IMRT, in the treatment of locally advanced sinonasal malignancy.

Data from retrospective studies suggest that IMRT or proton radiation therapy resulted in promising outcome in patients with sinonasal malignancy. To this date, no prospective study has been conducted to evaluate the outcome of sinonasal cancer treated with IMRT or proton radiation therapy. This Phase II trial is the first prospective study conducted to determine the treatment outcome and toxicity of IMRT or proton in the treatment of sinonasal cancer.

IMRT and proton radiation therapy are the two most established and most commonly employed advanced radiotherapy techniques for the treatment of sinonasal cancer. It is highly controversial whether one is superior to the other in terms of local control and toxicity outcome. It is also not clear if a subset of patients would benefit more from one treatment technology versus the other.

Due to the rarity and heterogeneity of sinonasal malignancies and the fact that proton beam is only available at a few centers in the United States, it is not feasible at present to do a Phase III study randomizing patients between IMRT and proton radiation therapy. In this study, a planned secondary analysis will be performed, comparing the treatment and toxicity outcome between IMRT and proton. The data on the IMRT and proton comparison from this trial will be used to design future multi-center prospective trials and to determine if randomized trial is necessary.

In this study, the treatment technique employed for an individual case will not be determined by the treating physician(s), but rather by the most advanced technology available at the treating institution for the treatment of the sinonasal cancer. At the Massachusetts General Hospital (MGH), proton beam therapy will be used for patients who meet the eligibility criteria. For institutions where protons are not available or institutions where the proton planning systems have not been optimized, IMRT exclusively will be used for the treatment of sinonasal cancer. Patient and tumor characteristics are expected to be comparable between IMRT- and proton- institutions

Subjects will receive daily proton radiation treatment as outpatients at the Francis H. Burr Proton Center at Massachusetts General Hospital. The subjects may also receive concurrent standard chemotherapy every week during their radiation therapy. This chemotherapy is considered standard treatment for their cancer and is not being done for research purposes.

In addition to daily radiation treatments, subjects will have the following tests every week: review of side effects; physical exam, including weight, height, neurological exam and vital signs; and blood tests, only for those subjects also receiving chemotherapy.

Subjects will be followed for 5 years after the completion of study treatment. The first follow-up visit will be 6-8 weeks after completion of study treatment. Additional follow-up visits will be performed every 3 months during the first 2 years following completion of radiation then every 6 month during years 3-5. At each follow-up visit, subjects will receive a physical exam, chest CT scan (at 1st follow-up visit then at least every 6 months), a CT or MRI tumor assessment (at 1st follow-up visit then at least every 6 months), quality-of-life questionnaire, hearing test, neuro-ophthalmology test, and neurocognitive test.

Intensity-Modulated or Proton Radiation Therapy for Sinonasal Malignancy

A Phase II Study of Intensity-Modulated or Proton Radiation Therapy for Locally Advanced Sinonasal Malignancy

To determine the local control rates with IMRT or proton radiation therapy at 2 years.

To determine the late visual-orbital late effects of IMRT or proton beam

To determine the regional control at 2 years after IMRT or proton

To determine the long-term survival at 5 years after IMRT or proton

To assess quality-of-life (QOL) outcomes after IMRT or proton

To determine the patterns of tumor relapse after IMRT or proton

To determine long-term local control after IMRT or proton

To determine long-term neurocognitive function after IMRT or proton

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
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	NCT05355753	Synovial Sarcom... Soft Tissue Sar...	CFT8634	12 Years -	C4 Therapeutics, Inc.
Intensity-Modulated or Proton Radiation Therapy for Sinonasal Malignancy	NCT01586767	Adenoid Cystic ... Squamous Cell C... Sinonasal Carci... Sinonasal Undif... Mucoepidermoid ... Schneiderian Ca... Myoepithelial C... Esthesioneurobl... Melanoma	Proton radiatio... Intensity-modul...	18 Years -	Massachusetts General Hospital

Spots Global Cancer Trial Database for myoepithelial carcinoma