Cabozantinib and Temozolomide for the Treatment of Unresectable or Metastatic Leiomyosarcoma or Other Soft Tissue Sarcoma

NCT04200443 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 5 other identifiers: 20664STU00210699NU 19S01P30CA060553NCI-2019-08090
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 5

Brief Summary

This phase II trial studies how well cabozantinib and temozolomide work in treating patients with leiomyosarcoma or other soft tissue sarcoma that cannot be removed by surgery (unresectable) or has spread to other places in the body (metastatic). Cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving cabozantinib and temozolomide may work better than either one alone in treating patients with leiomyosarcoma or other soft tissue sarcoma. Cabozantinib is an investigational drug, which means that it has not been approved by the United States (US) Food and Drug Administration (FDA) or any other regulatory agencies for sale or use by the public for the indication under investigation in this study.

Conditions

Stage IIIB Uterine Corpus Leiomyosarcoma AJCC v8; Stage IIIC Uterine Corpus Leiomyosarcoma AJCC v8; Stage IV Uterine Corpus Leiomyosarcoma AJCC v8; Stage IVA Uterine Corpus Leiomyosarcoma AJCC v8; Stage IVB Uterine Corpus Leiomyosarcoma AJCC v8; Unresectable Leiomyosarcoma; Unresectable Soft Tissue Sarcoma; Metastatic Leiomyosarcoma; Metastatic Soft Tissue Sarcoma; Stage IIIA Uterine Corpus Leiomyosarcoma AJCC v8; Stage III Uterine Corpus Leiomyosarcoma AJCC v8

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (PFS)

  Progression will be evaluated in this study using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1). Per RECIST v1.1 criteria, for target lesions, progression is defined as at least a 20% increase in the sum of the longest diameter or the appearance of one or more new lesions; For non-target lesions, progression is defined as the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. PFS will be the time from the start of treatment to the time of progression, unequivocal clinical deterioration, or death from any cause. The proportion of patients who had a PFS event was calculated.

  After the first 12 weeks of therapy

Secondary Outcomes (6)

• Presence of Response

  At weeks 6 and 12, then every 2 cycles up to 5 years

• Clinical Benefit Rate

  At weeks 6 and 12, then every 2 cycles up to 5 years

• Median Progression Free Survival

  Up to 5 years

• Overall Survival (OS)

  Up to 2 years

• Number of Participants With Adverse Events

  From time of first treatment up to the end of last treatment, up to 5 years

Study Arms (1)

Treatment (cabozantinib, temozolomide)

EXPERIMENTAL

Patients receive cabozantinib PO QD on days 1-28 and temozolomide PO QD on days 1-5. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Cabozantinib; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Drug: Temozolomide

Interventions

Cabozantinib DRUG

Given PO

Treatment (cabozantinib, temozolomide)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Treatment (cabozantinib, temozolomide)

Questionnaire Administration OTHER

Ancillary studies

Treatment (cabozantinib, temozolomide)

Temozolomide DRUG

Given PO

Also known as: CCRG-81045, Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-, M & B 39831, M and B 39831, Methazolastone, RP-46161, SCH 52365, Temcad, Temodal, Temodar, Temomedac, TMZ

Treatment (cabozantinib, temozolomide)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must have a histologically confirmed diagnosis of unresectable or metastatic:
• Uterine and non-uterine leiomyosarcoma
• Other soft tissue sarcoma (non-leiomyosarcoma)
• Note: Subjects with any one of the following soft tissue sarcoma histological subtypes will not be eligible for participation: alveolar soft-part sarcoma, dermatofibrosarcoma, gastrointestinal stromal tumor (GIST), Kaposi sarcoma, mixed mesodermal tumor/carcinosarcoma, rhabdomyosarcoma (embryonal and alveolar), and low grade (grade 1) sarcomas
• Subjects must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Subjects with 0 - 5 prior chemotherapy regimens for recurrent/metastatic disease are eligible. It will be up to the investigator to determine what constitutes a regimen in each case
• Subjects with prior next generation sequencing (NGS) reports completed on their tumor specimen will have this data collected
• Subjects must have measurable disease by RECIST 1.1
• Subjects must have adequate organ and bone marrow function, based upon meeting all of the following laboratory:
• White blood cell count \>= 2500/mm\^3 (\>= 2.5 GI/L)
• Absolute neutrophil count (ANC) \>= 1,500/mm\^3 (\>= 1.5 GI/L) without granulocyte colony stimulating factor support
• Hemoglobin \>= 9 g/dL (\>= 90 g/L)
• Platelets \>= 100,000/mm\^3 (\>= 100 GI/L) without transfusion
• Total bilirubin =\< 1.5 x upper limit of normal (ULN) (for subjects with Gilbert's disease =\< 3 x ULN)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SPGT\]) =\< 3 X upper limit of normal (ULN)

You may not qualify if:

• Inability to swallow tablets
• Previously identified allergy or hypersensitivity to components of the study treatment formulation or dacarbazine
• Subjects with a prior or concurrent malignancy whose natural history or treatment does have the potential to interfere with the safety or efficacy assessment of the investigational regiment are ineligible for this trial
• Pregnant or lactating females. Pregnant women are excluded from this study because cabozantinib and temozolomide are antineoplastic agents with potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with cabozantinib and temozolomide, breastfeeding should be discontinued if the mother is treated with cabozantinib and temozolomide
• Prior treatment with cabozantinib or temozolomide
• Receipt of any of the following:
• Any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 14 days before first dose of study treatment
• Any type of cytotoxic, biologic or other systemic anticancer therapy (including investigational) within 28 days before first dose of study treatment
• Radiation therapy for bone metastasis within 14 days before first dose of study treatment
• Any other radiation therapy within 28 days before first dose of study treatment
• Systemic treatment with radionuclides within 42 days before the first dose of study treatment
• Note: Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible
• Major surgery (e.g., GI surgery, removal or biopsy of brain metastasis) within 56 days before the first dose of study treatment
• Note: Complete wound healing from major surgery must have occurred 28 days before first dose and from minor surgery (e.g., simple excision, tooth extraction) at least 10 days before first dose. Subjects with clinically relevant ongoing complications from prior surgery are not eligible
• Corrected QT interval calculated by the Bazetts formula (QTcF) \> 500 ms per electrocardiogram (ECG) within 28 days before first dose of study treatment

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (5)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, 52242, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (1)

• Monga V, Okuno S, Van Tine B, Pollack SM, Weiss M, Hirbe A, Viveiros P, Schulte B, Attia S, Siontis B, Milhem MM, Charlson JA, Robinson S, Okunowo O, Frankel P, Woo D, Yoon J, Agulnik M. Cabozantinib and temozolomide in patients with unresectable or metastatic leiomyosarcoma and other soft tissue sarcomas: a multicentre, single-arm, lead-in phase 2 trial. Lancet Oncol. 2026 Feb;27(2):223-232. doi: 10.1016/S1470-2045(25)00654-0. Epub 2026 Jan 16.

  PMID: 41554272 DERIVED

MeSH Terms

Conditions

Leiomyosarcoma; Sarcoma

Interventions

cabozantinib; Temozolomide

Condition Hierarchy (Ancestors)

Neoplasms, Muscle Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Paul Frankel, Ph.D.
• Organization: City of Hope

pfrankel@coh.org

6262185265

Study Officials

• Janet Yoon, MD

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 13, 2019
• First Posted: December 16, 2019
• Study Start: January 14, 2020
• Primary Completion: April 4, 2025
• Study Completion (Estimated): September 10, 2026
• Last Updated: May 1, 2026
• Results First Posted: May 1, 2026

Record last verified: 2026-04

Locations

US (5)