Cabozantinib S-malate and Nivolumab in Treating Patients With Advanced, Recurrent, or Metastatic Endometrial Cancer
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|ClinicalTrials.gov Identifier: NCT03367741|
Recruitment Status : Suspended (Other - Data assessment)
First Posted : December 11, 2017
Last Update Posted : July 28, 2020
|Condition or disease||Intervention/treatment||Phase|
|Advanced Endometrial Carcinoma Metastatic Endometrial Carcinoma Recurrent Endometrial Carcinoma Stage III Uterine Corpus Cancer AJCC v7 Stage IIIA Uterine Corpus Cancer AJCC v7 Stage IIIB Uterine Corpus Cancer AJCC v7 Stage IIIC Uterine Corpus Cancer AJCC v7 Stage IIIC1 Uterine Corpus Cancer AJCC v7 Stage IIIC2 Uterine Corpus Cancer AJCC v7 Stage IV Uterine Corpus Cancer AJCC v7 Stage IVA Uterine Corpus Cancer AJCC v7 Stage IVB Uterine Corpus Cancer AJCC v7||Drug: Cabozantinib Drug: Cabozantinib S-malate Other: Laboratory Biomarker Analysis Biological: Nivolumab||Phase 2|
I. To evaluate the clinical anti-tumor activity of cabozantinib s-malate (XL184 ([cabozantinib]) and nivolumab based on progression free survival (PFS) in patients with advanced, recurrent or metastatic endometrial cancer previously treated with at least one line of platinum-based chemotherapy compared to patients receiving nivolumab alone.
I. To evaluate the efficacy of XL184 and nivolumab in terms of overall response rate (ORR) compared to nivolumab alone.
II. To evaluate overall survival (OS) of patients receiving XL184 and nivolumab compared to patients receiving nivolumab alone.
III. To evaluate the safety of combination treatment using XL184 and nivolumab in patients with advanced, recurrent metastatic endometrial cancer.
IV. To evaluate correlation between PD-L1 expression, CD3, CD4 and CD8 infiltrates and outcome (PFS, ORR, OS).
V. To compare PD-L1 expression, CD3, CD4 and CD8 infiltrates in the primary tumor (archival tissue) and in the tissue from baseline biopsy.
VI. To assess activity (PFS, ORR and OS) of nivolumab alone or in combination with XL184 according to microsatellite instability (MSI)/mismatched repair (MMR) status.
I. To assess activity (PFS, ORR and OS) of XL184 and nivolumab in patients progressed after previous exposure to anti PD-1, PD-L1 or PD-L2 agents or crossed-over from single agent nivolumab, and in patients with diagnosis of carcinosarcoma.
II. To compare microsatellite (MS) and MMR status, in the primary tumor (archival tissue) and in the tissue from baseline biopsy.
III. To assess the genomic and immune-markers landscape at baseline on tumor tissue and changes in immune landscape in peripheral blood during treatment and correlate with outcome.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM A: Patients receive cabozantinib s-malate orally (PO) once daily (QD) on days 1-28 and nivolumab intravenously (IV) over 30 minutes on days 1 and 15, then on day 1 beginning cycle 5.
ARM B: Patients receive nivolumab as in Arm A. Patients may cross-over to Arm A at the time of disease progression.
In both arms, cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30-37 days, then every 8-12 weeks.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||54 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Randomized Phase 2 Study of Cabozantinib in Combination With Nivolumab in Advanced, Recurrent Metastatic Endometrial Cancer|
|Actual Study Start Date :||January 26, 2018|
|Estimated Primary Completion Date :||January 23, 2021|
|Estimated Study Completion Date :||January 23, 2021|
Experimental: Arm A (cabozantinib s-malate, nivolumab)
Patients receive cabozantinib s-malate PO QD on days 1-28 and nivolumab IV over 30 minutes on days 1 and 15, then on day 1 beginning cycle 5. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: Cabozantinib S-malate
Other: Laboratory Biomarker Analysis
Experimental: Arm B (nivolumab)
Patients receive nivolumab as in Arm A. Patients may cross-over to Arm A at the time of disease progression. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
- Progression free survival (PFS) [ Time Frame: Up to 1 year ]
- Overall response rate (ORR) [ Time Frame: Up to 1 year ]Summary statistics, such as mean, median, counts and proportion, will be used to summarize the patients. Potential association between variables will be measured using Pearson correlation coefficients, chi-square tests, one- or two-sample t-tests or logistic regression analyses as appropriate. Non-parametric tests such as Spearman correlation coefficients, Fisher's exact tests and Wilcoxon rank sum test may be substituted if necessary. 95% percent confidence intervals will be constructed and selected results will be illustrated using figures and plots.
- Overall survival (OS) [ Time Frame: Up to 1 year ]Survival estimates will be computed using the Kaplan-Meier method.
- Incidence of adverse events [ Time Frame: Up to 1 year ]Frequency and severity of adverse events will be tabulated using counts and proportions detailing frequently occurring, serious and severe events of interest.
- PD-L1 expression, CD3, CD4 and CD8 analysis [ Time Frame: Up to 1 year ]Correlated with outcomes (PFS, ORR, OS). The log rank test, cox model or Chi-Square test will apply to access the association between PD-L1, CD3, CD4, CD8 expression and outcome (PFS, OS, ORR) where appropriate.
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): NCT03367741
|Principal Investigator:||Stephanie Lheureux||University Health Network Princess Margaret Cancer Center LAO|