NCT04214418

Study of Combination Therapy With the MEK Inhibitor, Cobimetinib, Immune Checkpoint Blockade, Atezolizumab, and the AUTOphagy Inhibitor, Hydroxychloroquine in KRAS-mutated Advanced Malignancies

Phase 1/2 Open-label Study of Combination Therapy With the MEK Inhibitor, Cobimetinib, Immune Checkpoint Blockade, Atezolizumab, and the AUTOphagy Inhibitor, Hydroxychloroquine in KRAS-mutated Advanced Malignancies

• Status: Terminated
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 27 (actual)
• Sponsor: Columbia University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This research study is for patients with an advanced cancer that carries a mutation in a gene called KRAS. Genes are parts of our DNA which carry instructions for a cell (the smallest component of an body part). In many cancers, the KRAS gene contains errors (mutations) which allows the tumors to grow. The purpose of this study is to determine if combination treatment with atezolizumab, cobimetinib, and hydroxychloroquine is safe, and if it will decrease the size of the tumor and prolong life in patients whose tumors contain this mutation. Cobimetinib and atezolizumab are both approved by the FDA for use in other cancers, but not in some cancer types being studied in this trial. Hydroxychloroquine is FDA approved to treat malaria and other conditions, but has also not been approved for these cancer types. Preliminary results have shown that this combination of drugs is effective at killing cancer cells and shrinking tumors in several KRAS-mutated cancers in animals.

Detailed description

The overall objective of this study is to investigate the safety and preliminary efficacy of combination therapy with cobimetinib and hydroxychloroquine, with or without atezolizumab in patients with KRAS-mutated advanced malignancies. Given that the pre-clinical and clinical benefit from this combination is from within poorly differentiated endocrine carcinoma (PDAC) animal models and human subjects with PDAC and duodenal cancer, we will include at least 12 of the 18 evaluable subjects from PDAC and/or colorectal malignancies. The phase 2 portion of the study will be amended after preliminary safety and efficacy results from phase 1 and other ongoing clinical trials have been analyzed and a summary incorporated within the protocol as an amendment including a rationale of the cohorts to be tested.

Conditions

• Gastrointestinal Cancer

Interventions

Type	Name	Description
DRUG	Cobimetinib	(40-60 mg) orally once daily (morning) on days 1-21 of each 28-day selective small molecule inhibitor for MEK1 and MEK2
DRUG	Hydroxychloroquine	(600mg) orally twice daily on days 1-28 of each 28-day cycle
DRUG	Atezolizumab	840 mg IV on Days 1 and 15 of each cycle humanized IgG1 monoclonal antibody (MAb)

Timeline

• Start date: 2020-02-12
• Primary completion: 2022-04-11
• Completion: 2022-07-01
• First posted: 2020-01-02
• Last updated: 2024-12-18
• Results posted: 2024-12-18

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study