Atezolizumab and Cabozantinib for the Treatment of Adolescents and Young Adults With Recurrent or Metastatic Osteosarcoma, TACOS Study

NCT05019703 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 2021-0409NCI-2021-06970
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 2

Brief Summary

This phase II trial studies the effect of atezolizumab and cabozantinib in treating adolescents and young adults with osteosarcoma that has come back (recurrent) or has spread to other places in the body (metastatic). Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving atezolizumab and cabozantinib may help to control the osteosarcoma.

Conditions

Locally Advanced Osteosarcoma; Metastatic Osteosarcoma; Recurrent Osteosarcoma; Refractory Osteosarcoma; Unresectable Osteosarcoma

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS)

  Defined by Response Evaluation Criteria in Solid Tumors (RECIST). Will estimate the PFS using the Kaplan-Meier method.

  From treatment onset to either disease progression or death from any cause, whichever occurs first, assessed up to 2 years

Secondary Outcomes (4)

• Objective response rate

  Up to 2 years

• PFS

  At 4 and 6 months

• Overall survival (OS)

  From treatment onset to death, assessed up to 2 years

• Incidence of adverse events

  Up to 2 years

Study Arms (1)

Treatment (atezolizumab, cabozantinib)

EXPERIMENTAL

Patients receive atezolizumab IV over 60 minutes on day 1 and cabozantinib PO QD on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Biological: Atezolizumab; Drug: Cabozantinib

Interventions

Atezolizumab BIOLOGICAL

Given IV

Also known as: MPDL 3280A, MPDL 328OA, MPDL-3280A, MPDL3280A, MPDL328OA, RG7446, RO5541267, Tecentriq

Treatment (atezolizumab, cabozantinib)

Cabozantinib DRUG

Given PO

Treatment (atezolizumab, cabozantinib)

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent form
• Age \>= 12 years at time of signing informed consent form
• Ability to comply with the study protocol, in the investigator's judgment
• Histologically confirmed diagnosis of osteosarcoma
• Metastatic or unresectable locally advanced disease
• Patients must have relapsed or become refractory to conventional therapy including some combination of cisplatin, doxorubicin, methotrexate, and/or ifosfamide
• Measurable disease per RECIST version (v)1.1 (Note: Previously irradiated lesions can be considered as measurable disease only if progressive disease has been unequivocally documented at that site since radiation)
• Availability of a representative tumor specimen for exploratory biomarker research. Archival samples are permitted if the tumor samples been obtained within 6 months prior to enrollment and the patient has not received intervening therapy
• A formalin-fixed paraffin-embedded (FFPE) tumor specimen in a paraffin block (preferred) or at least 15 slides containing unstained, freshly cut, serial sections should be submitted along with an associated pathology report prior to study enrollment. If only 10-14 slides are available, the patient may still be eligible for the study, after principal investigator confirmation has been obtained
• If archival tumor tissue is unavailable or is determined to be unsuitable for required testing, tumor tissue must be obtained from a biopsy performed at screening
• Eastern Cooperative Oncology Group (ECOG) of 0, 1 or 2. Use Karnofsky \>= 50 for patients \> 16 years of age and Lansky \>= 50 for patients =\< 16 years of age
• Body surface area (BSA) \>= 1 m\^2
• Life expectancy \>= 6 months
• Recovery to baseline or =\< grade 1 CTCAE v5 from toxicities related to any prior treatments, unless adverse events (AE\[s\]) are clinically nonsignificant and/or stable on supportive therapy
• Absolute neutrophil count (ANC) \>= 1.0 x 10\^9/L (1000/uL) without granulocyte colony-stimulating factor support (obtained within 14 days prior to initiation of study treatment)

You may not qualify if:

• Inability to swallow tablets
• Prior treatment with cabozantinib
• Prior treatment with immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies if given in combination with a VEGF-targeted tyrosine kinase inhibitor (TKI). Patients receiving prior anti-PD-1, anti-PD-L1, with or without anti-CTLA-4 antibodies will not be excluded
• Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before first dose of study treatment
• Receipt of any type of cytotoxic, biologic or other systemic anticancer therapy (including investigational) within 4 weeks before first dose of study treatment
• Radiation therapy for bone metastasis within 2 weeks or any other radiation therapy within 4 weeks before first dose of study treatment. Systemic treatment with radionuclides within 6 weeks before first dose of study treatment. Patients with clinically relevant ongoing complications from prior radiation therapy are not eligible
• Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks prior to first dose of study treatment after radiotherapy or at least 4 weeks prior to first dose of study treatment after major surgery (e.g., removal or biopsy of brain metastasis). Patients must have complete wound healing from major surgery or minor surgery before first dose of study treatment. Eligible patients must be neurologically asymptomatic and without corticosteroid treatment at the time of first dose of study treatment
• History of leptomeningeal disease
• Uncontrolled tumor-related pain
• Patients requiring pain medication must be on a stable regimen at study entry
• Symptomatic lesions (e.g., bone metastases or metastases causing nerve impingement) amenable to palliative radiotherapy should be treated prior to enrollment. Patients should be recovered from the effects of radiation
• Asymptomatic metastatic lesions that would likely cause functional deficits or intractable pain with further growth (e.g., epidural metastasis that is not currently associated with spinal cord compression) should be considered for loco-regional therapy if appropriate prior to enrollment
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
• Patients with indwelling catheters (e.g., PleurX) are allowed
• Concomitant anticoagulation with coumarin agents (e.g., warfarin), direct thrombin inhibitors (e.g., dabigatran), direct factor Xa inhibitor betrixaban, or platelet inhibitors (e.g., clopidogrel). Allowed anticoagulants are the following:

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (2)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

M D Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• M D Anderson Cancer Center

MeSH Terms

Conditions

Osteosarcoma

Interventions

atezolizumab; cabozantinib

Condition Hierarchy (Ancestors)

Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma

Study Officials

• John A Livingston, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

John A Livingston, MD

CONTACT

(713) 792-3626; jalivingston@mdanderson.org

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: August 18, 2021
• First Posted: August 25, 2021
• Study Start: April 25, 2023
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: April 17, 2026

Record last verified: 2026-04

Locations

US (2)