Metastatic Malignant Skin Neoplasm Clinical Trial
Official title:
Short-Term Fasting Prior to Standard Checkpoint Blockade Using PD-1/PD-L1 Inhibition: A Pilot Safety and Feasibility Study
This trial studies the side effects of short-term fasting in patients with skin malignancy that has spread to other places in the body (advanced or metastatic) treated with a PD-L1 or PD-1 inhibitor. Immunotherapy with monoclonal antibodies, such as pembrolizumab, nivolumab, cemiplimab, avelumab, atezolizumab, or durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Undergoing short-term fasting prior to treatment with one of these PD-L1 or PD-1 inhibitors may potentially reduce the side effects of immunotherapy or even improve the effectiveness of immunotherapy in patients with skin malignancy.
PRIMARY OBJECTIVES: I. To evaluate the safety and feasibility of short term fasting in combination with PD-1 inhibition therapy for patients with advanced malignancy. Ia. To estimate the percentage of patients who adhere completely to short term fasting (STF) in combination with PD-1 inhibition therapy for 3 cycles. Ib. To estimate the percentage of patients who develop unacceptable fasting-related toxicity. SECONDARY OBJECTIVES: I. To measure how many patients can adhere with STF for at least 2 cycles in combination with PD-1 inhibition. Ia. To estimate the percentage of patients who adhere to STF in combination with PD-1 inhibition therapy for at least 2 cycles, or a total of at least 6 out of 9 days. II. To measure all grades of fasting-related toxicity. IIa. To estimate the percentage of patients who develop any grades of fasting-related toxicity, including acceptable fasting-related toxicity. EXPLORATORY OBJECTIVES: I. The efficacy of combining STF with PD-1/PD-L1 inhibition will be assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 response rate, as measured at the time of tumor assessment after 3 cycles of treatment. II. The immune-related toxicity of combining STF with PD-1/PD-L1 inhibition will be recorded at the start of each cycle, and graded per Common Terminology Criteria for Adverse Events (CTCAE) v 4.0. III. Quality of life during STF combined with PD-1/PD-L1 inhibition will be recorded using the Functional Assessment of Cancer Therapy - General (FACT-G) version 4, questionnaire tool. IV. Fasting-related biomarkers to measure the impact of STF during PD-1/PD-L1 inhibition include measurement of serum insulin/IGF-1, PI3K/AKT/mTOR signaling, MAPK pathway signaling, and markers of oxidative stress. V. Immune biomarkers will be analyzed using immunohistochemistry and ribonucleic acid (RNA) expression studies. OUTLINE: Patients undergo STF for 47-48 hours prior to immunotherapy and for 24 hours after immunotherapy with standard of care pembrolizumab given intravenously (IV) over 30 minutes, nivolumab IV over 30 minutes, cemiplimab IV over 30 minutes, avelumab IV over 60 minutes, atezolizumab IV over 60 minutes, or durvalumab IV over 60 minutes on day 3. Treatment repeats every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up in 3-6 weeks. ;
| Status | Clinical Trial | Phase | |
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| Recruiting |
NCT06349642 -
Predicting Response to Immune Checkpoint Inhibitors Across Solid Tumors Using a Live Tumor Diagnostic Platform
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