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Advanced Malignant Skin NeoplasmPhase 1NCT04387084

Short-term Fasting Prior to PD-1/PD-L1 Inhibitor Therapy for of Advanced or Metastatic Skin Malignancy

A Phase 1 study testing Atezolizumab, Avelumab and Cemiplimab in people with Advanced Malignant Skin Neoplasm and Metastatic Malignant Skin Neoplasm, run by University of Southern California at 2 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Atezolizumab, Avelumab and Cemiplimab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
10 participants
Where
2 sitesUnited States
Study dates
12 Aug 2020to 31 Mar 2028
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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
  • Additional checkpoint inhibitors may be considered, with the approval of the PI, and will require a future amendment to the protocol.
  • Advanced or metastatic cutaneous tumor with measurable disease evaluable by RECIST criteria. Patients with other solid tumors may be eligible if they have a cutaneous metastasis amenable to biopsy (with approval of PI only)
  • No more than 2 lines of prior systemic therapy (not including neoadjuvant or adjuvant therapy)
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Absolute neutrophil count >= 1,000/mcL
  • Absolute lymphocyte count >= 500/mcL
  • Hemoglobin >= 8.0 g/dL
  • Platelets >= 75,000/mcl
  • Total bilirubin =< 1.5 x institutional upper limit of normal
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x institutional upper limit of normal
  • Creatinine =< 1.8 mg/dl or calculated creatinine clearance > 40 ml/min
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
  • Has not undergone a hysterectomy or bilateral oophorectomy; or
  • Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)
  • Body mass index (BMI) >= 18.5
  • Ability to understand and the willingness to sign a written informed consent and comply with short-term fasting during study and other study-related procedures

Who cannot join

  • 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
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  • 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
  • Positive pregnancy test, active pregnancy or nursing/breast-feeding, due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants
  • History of solid organ or bone marrow transplantation

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Los Angeles General Medical Center

    Los Angeles, California, 90033

  • USC / Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

Other trials in United States

About this study

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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:

  1. 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.

  1. 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.

Medical subject headings
Skin Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AtezolizumabDrug

    Also called MPDL 3280A, MPDL 328OA, MPDL-3280A, MPDL3280A

    Given IV

  • AvelumabDrug

    Also called Bavencio, MSB-0010718C, MSB0010718C

    Given IV

  • CemiplimabBiological

    Also called Cemiplimab RWLC, Cemiplimab-rwlc, Libtayo, REGN2810

    Given IV

  • DurvalumabBiological

    Also called Imfinzi, Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer, MEDI-4736, MEDI4736

    Given IV

  • NivolumabBiological

    Also called BMS-936558, MDX-1106, NIVO, ONO-4538

    Given IV

  • PembrolizumabBiological

    Also called Keytruda, Lambrolizumab, MK-3475, SCH 900475

    Given IV

  • Quality-of-Life AssessmentOther

    Also called Quality of Life Assessment

    Ancillary studies

  • Short-Term FastingOther

    Also called Intermittent Fasting, Short-term Intermittent Fasting

    Undergo STF

  • DostarlimabBiological

    Also called Jemperli, dostarlimab-gxly

    Given IV

  • RetifanlimabBiological

    Also called Zynyz, retifanlimab-dlwr, MGA012, INCMGA-00012

    Given IV

  • ToripalimabBiological

    Also called Loqtorzi, toripalimab-tpzi, Tuoyi, ZYTORVI

    Given IV

  • TislelizumabBiological

    Also called Tevimbra, tislelizumab-jsgr, BGB-A317

    Given IV

Study groups in NCT04387084
Study groupRoleWhat they receive
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.
Receives: Drug: Atezolizumab; Drug: Avelumab; Biological: Cemiplimab; Biological: Durvalumab; Biological: Nivolumab; Biological: Pembrolizumab; Other: Quality-of-Life Assessment; Other: Short-Term Fasting; Biological: Dostarlimab; Biological: Retifanlimab; Biological: Toripalimab; Biological: Tislelizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Up to 3 cycles (each cycle is 21 days)

  2. 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.

    Measured: At the start of each cycle (prior to immunotherapy infusion), up to 3 cycles (each cycle is 21 days)

Secondary outcomes (2)

  1. Percentage of patients who can partially adhere to 3 cycles of STF (9 days of fasting)

    Partial adherence will be defined as patients who adhere to STF (consumption of less than 200 kCal per 24 hours) in combination with PD-1/PD-L1 inhibition therapy for at least 2 cycles of therapy, or at least 6 out of total 9 days of fasting. Will be described with descriptive statistics.

    Measured: Up to 3 cycles (each cycle is 21 days)

  2. Incidence of acceptable fasting related toxicity

    Fasting-related toxicity is to be recorded at the start of each cycle (prior to immunotherapy infusion), and graded per CTCAE v 4.0. Incidence of adverse events related to fasting, including acceptable fasting-related toxicity, will be evaluated.

    Measured: At the start of each cycle (prior to immunotherapy infusion), up to 3 cycles (each cycle is 21 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 May 2020
  2. Study start12 Aug 2020
  3. Primary completion31 Mar 2027 (estimated)
  4. Study completion31 Mar 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Supportive care
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04387084
Sponsor's protocol ID
0S-20-1
Other IDs
NCI-2020-01590, 0S-20-1, P30CA014089
Status last verified
Sep 2026
First submitted
9 May 2020
Last updated
21 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Atezolizumab, Avelumab and Cemiplimab in people with Advanced Malignant Skin Neoplasm and Metastatic Malignant Skin Neoplasm, run by University of Southern California at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 32 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 21 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of patients completely adhering to 3 cycles of short term fasting (STF) (9 days of fasting) (time frame: Up to 3 cycles (each cycle is 21 days)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04387084.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Sep 2026.

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