Short-term Fasting Prior to PD-1/PD-L1 Inhibitor Therapy for of Advanced or Metastatic Skin Malignancy
Short-Term Fasting Prior to Standard Checkpoint Blockade Using PD-1/PD-L1 Inhibition: A Pilot Safety and Feasibility Study
3 other identifiers
interventional
10
1 country
2
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Aug 2020
Longer than P75 for phase_1
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 9, 2020
CompletedFirst Posted
Study publicly available on registry
May 13, 2020
CompletedStudy Start
First participant enrolled
August 12, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 12, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
August 12, 2027
March 23, 2026
March 1, 2026
6 years
May 9, 2020
March 18, 2026
Conditions
Outcome Measures
Primary Outcomes (2)
Percentage of patients completely adhering to 3 cycles of short term fasting (STF) (9 days of fasting)
Complete adherence will be defined as patients who adhere to STF (consumption of less than 200 kilocalorie \[kCal\] per 24 hours) in combination with PD-1/PD-L1 inhibition therapy for all 3 cycles of therapy (total of 9 days of fasting). Will be described with descriptive statistics.
Up to 3 cycles (each cycle is 21 days)
Percentage of patients who develop unacceptable fasting-related toxicity
Will be graded per Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. The safety benchmark will be set at 0 subjects in the total cohort experiencing fasting-related toxicity, i.e., if even 1 patient experiences unacceptable fasting-related toxicity, the study will be discontinued.
At the start of each cycle (prior to immunotherapy infusion), up to 3 cycles (each cycle is 21 days)
Secondary Outcomes (2)
Percentage of patients who can partially adhere to 3 cycles of STF (9 days of fasting)
Up to 3 cycles (each cycle is 21 days)
Incidence of acceptable fasting related toxicity
At the start of each cycle (prior to immunotherapy infusion), up to 3 cycles (each cycle is 21 days)
Study Arms (1)
Treatment (STF, PD-1/PD-L1 inhibitor)
EXPERIMENTALPatients undergo STF for 47-48 hours prior to immunotherapy and for 24 hours after immunotherapy with standard of care pembrolizumab given IV over 30 minutes, nivolumab IV over 30 minutes, cemiplimab IV over 30 minutes, dostarlimab IV over 30 minutes, retifanlimab IV over 30 minutes, toripalimab IV over 60 minutes, 30 minutes for subsequent dose, tislelizumab IV over 60 minutes for 1st dose, 30 minutes for subsequent doses, 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.
Interventions
Given IV
Given IV
Given IV
Given IV
Given IV
Given IV
Ancillary studies
Undergo STF
Given IV
Given IV
Given IV
Given IV
Eligibility Criteria
You may qualify if:
- Histologically confirmed solid tumor malignancy for which PD-1/PDL1 inhibition based immunotherapy is recommended as standard of care therapy, as monotherapy or in combination with other checkpoint inhibitors. Acceptable PD-1/PD-L1 inhibitors include\*:
- Pembrolizumab
- Nivolumab
- Cemiplimab
- Dostarlimab
- Retifanlimab
- Toripalimab
- Tislelizumab
- Atezolizumab
- Avelumab
- Durvalumab \* Additional PD-1/PD-L1 inhibitors may be considered, with the approval of the principal investigator (PI), and will require a future amendment to the protocol
- Other immune checkpoint inhibitors (such as those targeting CTLA-4, LAG-3, etc) that may be used in combination with PD-1/PD-L1 inhibitors as standard of care therapy include\*\*:
- Ipilimumab
- Tremelimumab
- Relatlimab
- +17 more criteria
You may not qualify if:
- Patients with history of diabetes mellitus are not eligible for this study
- Note: patients with pre-diabetes or a history of diabetes which subsequently resolves, who are not taking metformin or any other diabetes medications are eligible
- Patients with recent significant or unexplained weight loss that the investigator feels may pose an unacceptable risk for enrollment should be excluded. (Candidates who are overweight and have intentionally lost weight via diet or exercise should be excluded, for instance)
- Subjects on medications that may not be safely stopped during the fasting portion of the study, or which may not be safely consumed without food
- Prior history of syncope with caloric restriction in the past or other medical comorbidity which would make fasting potentially dangerous
- Prior treatment with any agent that blocks the PD-1 or PD-L1 pathway
- Prior treatment with other immune modulating agents within fewer than 4 weeks, prior to the first dose of PD-1/PD-L1 inhibition. Examples of immune modulating agents include blockers of CTLA-4, 4-1BB, OX-40, therapeutic vaccines, or cytokine therapies
- Patients must not be receiving other concomitant biologic therapy, hormonal therapy, chemotherapy, other anti-cancer therapy or any other investigational agents while on this protocol
- Radiation therapy, non-cytotoxic agents or investigational agents in the 4 weeks prior to the first dose of PD-1/PD-L1 inhibition
- Immunosuppressive systemic corticosteroids equivalent to prednisone 10 mg or greater in the 14 days prior to the first dose of PD-1/PD-L1 inhibition
- Any major surgery within 14 days prior to the first dose of PD-1/PD-L1 inhibition. Patients must have recovered from any major complications before registration
- Active autoimmune disease requiring systemic treatment in the past 2 years (i.e. use of disease modifying agents or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc) is not considered a form of systemic treatment
- Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to PD-1 or PD-L1 inhibitor
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- +2 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University of Southern Californialead
- National Cancer Institute (NCI)collaborator
Study Sites (2)
Los Angeles General Medical Center
Los Angeles, California, 90033, United States
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Gino K In, MD
University of Southern California
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- SUPPORTIVE CARE
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 9, 2020
First Posted
May 13, 2020
Study Start
August 12, 2020
Primary Completion (Estimated)
August 12, 2026
Study Completion (Estimated)
August 12, 2027
Last Updated
March 23, 2026
Record last verified: 2026-03