Atezolizumab and Cabozantinib for the Treatment of Adolescents and Young Adults With Recurrent or Metastatic Osteosarcoma, TACOS Study
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|ClinicalTrials.gov Identifier: NCT05019703|
Recruitment Status : Not yet recruiting
First Posted : August 25, 2021
Last Update Posted : March 2, 2022
|Condition or disease||Intervention/treatment||Phase|
|Locally Advanced Osteosarcoma Metastatic Osteosarcoma Recurrent Osteosarcoma Refractory Osteosarcoma Unresectable Osteosarcoma||Biological: Atezolizumab Drug: Cabozantinib||Phase 2|
I. To assess the efficacy of cabozantinib in combination with atezolizumab in recurrent/metastatic osteosarcoma as determined by the progression-free survival (PFS) defined as the time from treatment onset to either disease progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST) or death from any cause, whichever occurs first.
I. To estimate the objective response rate (ORR) by RECIST 1.1 criteria, immune-based (i)RECIST, and immune-modified (im)RECIST.
II. To estimate the progression-free survival (PFS) rates at 4 months and 6 months.
III. To estimate the overall survival (OS) in patients with recurrent/metastatic osteosarcoma receiving cabozantinib + atezolizumab.
IV. To evaluate the safety and tolerability of the combination as assessed by toxicity rates according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
I. To determine the expression of selected biomarkers including PD-1/PD-L1, MET, and VEGFR in pre-treatment and on-treatment tumor biopsy specimens.
II. To assess the immunologic response by change in immune infiltrate in tumors from baseline and on-treatment biopsy specimens and correlate findings with clinical benefit/response to therapy.
III. To characterize and quantify immunologic changes in peripheral blood and correlate with clinical benefit/treatment response.
Patients receive atezolizumab intravenously (IV) over 60 minutes on day 1 and cabozantinib orally (PO) once daily (QD) on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up within 30 days, then every 3 months for 2 years.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||40 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 2 Trial of Atezolizumab and Cabozantinib in Adolescents and Young Adults With Recurrent/Metastatic Osteosarcoma (TACOS)|
|Estimated Study Start Date :||June 1, 2022|
|Estimated Primary Completion Date :||December 31, 2027|
|Estimated Study Completion Date :||December 31, 2027|
Experimental: Treatment (atezolizumab, cabozantinib)
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.
- Progression-free survival (PFS) [ Time Frame: From treatment onset to either disease progression or death from any cause, whichever occurs first, assessed up to 2 years ]Defined by Response Evaluation Criteria in Solid Tumors (RECIST). Will estimate the PFS using the Kaplan-Meier method.
- Objective response rate [ Time Frame: Up to 2 years ]Estimated by RECIST 1.1 criteria, immune-based RECIST, and immune-modified RECIST.
- PFS [ Time Frame: At 4 and 6 months ]Will be estimated along with a 95% confidence interval. Will be estimated using the Kaplan-Meier method. Log-rank test will be performed to test the difference in survival between groups. Regression analyses of survival data based on the Cox proportional hazards model will be conducted on PFS. The proportional hazards assumption will be evaluated graphically and analytically, and regression diagnostics (e.g., martingale and Shoenfeld residuals) will be examined to ensure that the models are appropriate.
- Overall survival (OS) [ Time Frame: From treatment onset to death, assessed up to 2 years ]Will be estimated along with a 95% confidence interval. Will be estimated using the Kaplan-Meier method. Log-rank test will be performed to test the difference in survival between groups. Regression analyses of survival data based on the Cox proportional hazards model will be conducted on OS. The proportional hazards assumption will be evaluated graphically and analytically, and regression diagnostics (e.g., martingale and Shoenfeld residuals) will be examined to ensure that the models are appropriate.
- Incidence of adverse events [ Time Frame: Up to 2 years ]Common Terminology Criteria for Adverse Events version 5.0. Toxicity data will be summarized by frequency tables. For the toxicity endpoint, per-treated analysis will be used to include any patient who received the treatment regardless of the eligibility nor the duration or dose of the treatment received. Toxicity rate will be estimated with 95% credible interval.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05019703
|United States, Texas|
|M D Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Contact: John A. Livingston 713-792-3626 email@example.com|
|Principal Investigator: John A. Livingston|
|Principal Investigator:||John A Livingston||M.D. Anderson Cancer Center|