Cabozantinib With Pemetrexed in Advanced Non-small Cell Lung Cancer, Urothelial Cancer and Malignant Mesothelioma

Study Overview
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Brief Summary
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This study will combine cabozantinib with pemetrexed to treat patients with non-small cell lung cancer, urothelial cancer and advanced malignant mesothelioma. This study will test the safety of both drugs used together and see what effect (good or bad) it has no participants and their cancer.

Official Title
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Phase I Study of Cabozantinib in Combination With Pemetrexed in Advanced Non-squamous Non-small Cell Lung Cancer (NSCLC), Urothelial Cancer and Advanced Malignant Mesothelioma

Conditions
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Non Small Cell Lung Cancer, Non-squamous Non-small-cell Lung Cancer, Urothelial Carcinoma, Malignant Mesothelioma

Intervention / Treatment
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* Drug: Cabozantinib
* Drug: Pemetrexed


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Locally advanced NSCLC, urothelial cancer or malignant mesothelioma. 18 years or older. At least one prior chemotherapy before entering in this trial. Not pregnant or breastfeeding. Exclusion Criteria: Prior treatment with cabozantinib. Currently receiving cancer treatment (last dose 2 weeks prior to enrollment in study). History of bleeding disorder/bleeding history within 12 weeks before first study treatment dose.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cabozantinib + Pemetrexed<br>Pemetrexed 500mg/m2 IV day 1 of each 21 day cycle + Cabozantinib 20-60mg by mouth once a day. | Drug: Cabozantinib<br>* start at 20mg then increase by 20mg every cycle or until there's a dose-limiting toxicity.<br>Drug: Pemetrexed<br>* Start with 400mg/m2, then increase and maintain 500mg/m2 unless dose-limiting toxicity.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess the maximum tolerated dose (MTD) of cabozantinib in combination with pemetrexed | Dose-limiting toxicity of grade 3 or higher using CTCAE 5 | 4 weeks or 28 days assessment. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess objective response rate (RR) | RR measured by Tumor response evaluation with RECIST | To be measured through study completion; an average of 1 year. | 
| Progression-free survival (PFS) | PFS measured from the time of study treatment to the date of progression. | To be measured through study completion; an average of 1 year. | 
| Overall survival (OS). | Measured from the time of start of treatment to time of death or time of last assessment. | OS measured through study completion, and an average of 1 year |