Neoplasms

All Conditions

Infections

Symptoms and General Pathology

Rare Diseases

Carcinoma

Carcinoma, Merkel Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Communicable Diseases

Polyomavirus Infections

Virus Diseases

DNA Virus Infections

Tumor Virus Infections

Carcinoma, Neuroendocrine

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Adenocarcinoma

Neoplasms, Nerve Tissue

Merkel Cell Carcinoma

Neuroendocrine Tumor

Neuroepithelioma

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Pembrolizumab

Immunomodulating Agents

Immunoglobulins

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Patients receive pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

Patients receive pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo SBRT for 3 doses during cycle 1.

Stereotactic Body Radiation Therapy

Jason J Luke

This randomized phase II trial studies how well pembrolizumab with or without stereotactic body radiation therapy works in treating patients with Merkel cell cancer that has spread to other places in the body (advanced). Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Stereotactic body radiation therapy uses special equipment to position a patient and deliver radiation to tumors with high precision. This method can kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. Giving pembrolizumab with stereotactic body radiation therapy may work better in treating patients with Merkel cell cancer.

PRIMARY OBJECTIVE:

I. To describe the progression-free survival (PFS) of stereotactic body radiation therapy (SBRT) + pembrolizumab (MK-3475) compared to pembrolizumab (MK-3475) alone in advanced/metastatic Merkel cell carcinoma (MCC) patients.

SECONDARY OBJECTIVES:

I. To describe the PFS of SBRT + MK-3475 compared to pembrolizumab (MK-3475) alone across Response Evaluation Criteria in Solid Tumors (RECIST) measurable (including both radiated and non-radiated) cancer deposits.

II. To describe the overall response rate of SBRT + pembrolizumab (MK-3475) compared to pembrolizumab(MK-3475) alone in both radiated and in non-radiated deposit(s).

III. To determine the PFS at 6 months of SBRT + pembrolizumab (MK-3475) compared to pembrolizumab (MK-3475) alone across all cancerous deposits by RECIST.

IV. To determine the rate of grade \> 3-4 adverse events, by organ system, by Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0.

V. To determine the local control of SBRT treated tumors. VI. To calculate delivered radiation dose using cone-beam computed tomography (CT) images collected on the radiation treatment table in the final treatment position.

CORRELATIVE SCIENCE OBJECTIVES:

I. To test the utility of CT-based radiomics to predict radiation-induced pneumonitis and true delivered dose of SBRT based on cone beam collected imaging and diagnostic scans.

II. Biobanking for future correlative science projects.

OUTLINE: Patients are randomized to 1 of 2 groups.

GROUP I: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

GROUP II: Patients receive pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo SBRT for 3 doses during cycle 1.

After completion of study treatment, patients are followed up every 6 months for up to 5 years.

Testing the Addition of Radiation Therapy to Immunotherapy for Merkel Cell Carcinoma

A Randomized Phase II Study of Anti-PD1 Antibody [MK-3475 (Pembrolizumab)] Alone Versus Anti-PD1 Antibody Plus Stereotactic Body Radiation Therapy in Advanced Merkel Cell Carcinoma

Will compare PFS in non-radiated lesion(s) of patients receiving either (a) stereotactic body radiation therapy (SBRT) + pembrolizumab compared to (b) pembrolizumab alone in patients with advanced Merkel cell carcinoma. Kaplan- Meier curves will be constructed and median PFS times will be calculated for each arm. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

Same as the primary endpoint, but includes both irradiated and non-radiated lesions. It is a time to event endpoint and will be evaluated using the Kaplan- Meier method. Median PFS times will be calculated for each arm and a cox proportional hazards model will be constructed to determine if there is a PFS benefit for patients receiving SBRT + pembrolizumab compared to pembrolizumab alone.

Defined as partial response (PR) on 2 consecutive evaluations. Response rates will be calculated and compared across treatment arms utilizing a chi-square test.

The rates of success will be calculated and compared across treatment arms utilizing a chi-square test.

Graded according to National Cancer Institute's Common Terminology Criteria for Adverse Events, version 5.0. Maximum grade adverse events will be summarized by treatment arm in a tabular setting.

The protocol irradiated tumors are considered to be controlled if they have no evidence of progression. No evidence of progression is defined as complete response, PR, or stable disease. Local control of the protocol-irradiated tumor will be described using the Kaplan-Meier technique.

Radiation doses will be summarized descriptively and compared to the planned dose.

National Cancer Institute (NCI)

Group I (Pembrolizumab)

Stereotactic Body Radiation Therapy: Undergo SBRT

Group II (Pembrolizumab, SBRT)

Patients receive pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.\>

\> Pembrolizumab: Given IV

Patients receive pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo SBRT for 3 doses during cycle 1.\> \> Pembrolizumab: Given IV\>

\> Stereotactic Body Radiation Therapy: Undergo SBRT

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Dr. Jason Luke

Patients receive pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

\>

\> Pembrolizumab: Given IV

Patients receive pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo SBRT for 3 doses during cycle 1.

\>

\> Pembrolizumab: Given IV

\>

\> Stereotactic Body Radiation Therapy: Undergo SBRT

Progression-free Survival (PFS)

PFS Among All Response Evaluation Criteria in Solid Tumors Lesions

Overall Response Rate

Progression-free Survival

Incidence of Adverse Events

Group I did not receive radiation per protocol.

PFS for Lesions Chosen for Radiation Prior to Randomization

Planned Dose Cycle 1

Actual Dose Cycle 1

Planned Dose Cycle 2

Actual Dose Cycle 2

Delivered Radiation Dose Using Cone-beam Computed Tomography (CT) Images

Overall Study

Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 17 cycles in the absence of disease progression or unacceptable toxicity. Patients may also undergo standard of care radiation therapy within 14 days of day 1, cycle 1. Patients undergo PET-CT, CT, or MRI throughout the trial. Patients may also undergo blood sample collection as clinically indicated at the discretion of the treating investigator.

Patients receive standard of care observation every 3 months for 1 year, and then every 6 months for 5 years. Patients may also undergo standard of care radiation therapy within 14 days of day 1, cycle 1. Patients undergo PET-CT, CT, or MRI throughout the trial. Patients may also undergo blood sample collection as clinically indicated at the discretion of the treating investigator.

Best Practice

Biospecimen Collection

Computed Tomography

Magnetic Resonance Imaging

Positron Emission Tomography

Radiation Therapy

Janice Mehnert

This phase III trial studies how well pembrolizumab works compared to standard of care observation in treating patients with stage I-III Merkel cell cancer that has been completely removed by surgery (resected). Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

PRIMARY OBJECTIVE:

I. To compare recurrence free survival (RFS) and overall survival (OS) as co-primary endpoints across the two arms.

SECONDARY OBJECTIVES:

I. To evaluate adverse events. II. To evaluate distant metastasis free survival (DMFS). III. To evaluate the impact of radiation on clinical outcomes (OS, RFS, DMFS).

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1 of each cycle. Treatment repeats every 21 days for up to 17 cycles in the absence of disease progression or unacceptable toxicity. Patients may also undergo standard of care radiation therapy within 14 days of day 1, cycle 1. Patients undergo positron emission tomography (PET)-computed tomography (CT), CT, or magnetic resonance imaging (MRI) throughout the trial. Patients may also undergo blood sample collection as clinically indicated at the discretion of the treating investigator.

ARM B: Patients receive standard of care observation every 3 months for 1 year, and then every 6 months for 5 years. Patients may also undergo standard of care radiation therapy within 14 days of day 1, cycle 1. Patients undergo PET-CT, CT, or MRI throughout the trial. Patients may also undergo blood sample collection as clinically indicated at the discretion of the treating investigator.

After completion of study treatment, patients are followed up every 3-6 months for 5 years from the date of registration.

Testing Pembrolizumab Versus Observation in Patients With Merkel Cell Carcinoma After Surgery, STAMP Trial

STAMP: Surgically Treated Adjuvant Merkel Cell Carcinoma With Pembrolizumab, a Phase III Trial

An intention-to-treat (ITT) analysis using the stratified log-rank test will be performed to compare overall survival (OS) and RFS between the two arms.

An ITT analysis using the stratified log-rank test will be performed to compare OS and RFS between the two arms.

RFS in each arm will be evaluated by radiation treatment status (radiation versus \[vs.\] no radiation therapy). The analysis will be a planned post-hoc analysis with primary goal of examining whether use of post-operative radiation therapy is associated with RFS. Cox multivariate models for RFS will be developed to evaluate the impact of radiation therapy while adjusting for pembrolizumab treatment and clinical/ pathological factors. The treatment fields and dose data will also be included in the Cox model as covariates. Secondary analyses for radiation therapy (RT) will examine factors associated with use of post-operative RT. Multivariate logistic regression models (radiation therapy vs. no radiation therapy) will be developed to evaluate the associations with demographic, clinical/pathologic, and treatment-related factors and pembrolizumab treatment.

OS in each arm will be evaluated by radiation treatment status (radiation vs. no radiation therapy). The analysis will be a planned post-hoc analysis with primary goal of examining whether use of post-operative radiation therapy is associated with OS. Cox multivariate models for OS will be developed to evaluate the impact of radiation therapy while adjusting for pembrolizumab treatment and clinical/ pathological factors. The treatment fields and dose data will also be included in the Cox model as covariates. Secondary analyses for radiation therapy will examine factors associated with the the use of post-operative RT. Multivariate logistic regression models (radiation therapy vs. no radiation therapy) will be developed to evaluate the associations with demographic, clinical/pathologic, and treatment-related factors and pembrolizumab treatment.

DMFS will be evaluated by treatment arms. If there is no distant metastasis, cases will be censored at the time of last assessment.

Measured per Common Terminology Criteria for Adverse Events version 5.0. Adverse events from each arm will be summarized and compared using Fisher's exact test.

Skin and Connective Tissue Diseases

Melanoma

Carcinoma, Squamous Cell

Neoplasm Metastasis

Carcinoma, Basal Cell

Melanoma, Cutaneous Malignant

Skin Neoplasms

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Diseases

Neoplastic Processes

Neoplasms, Basal Cell

Anti-Inflammatory Agents

Nivolumab

Tacrolimus

Antibodies, Monoclonal

Prednisone

Ipilimumab

Cortisone

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Immunosuppressive Agents

Immunologic Factors

Calcineurin Inhibitors

Enzyme Inhibitors

Patients receive tacrolimus PO BID and prednisone PO QD. Within 28 days, patients then receive nivolumab IV over 30 minutes on day 1. Cycles repeat every 4 weeks for up to 24 cycles (96 weeks) in the absence of disease progression or unacceptable toxicity.

Patients who experience PD or patients who have experienced allograft loss at 16 weeks receive nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes on day 1. Patients also receive tacrolimus PO BID and prednisone PO QD. Cycles repeat every 3 weeks for 4 cycles (12 weeks) in the absence of disease progression or unacceptable toxicity. Starting 6 weeks later, patients receive nivolumab IV over 30 minutes every 4 weeks for up to 21 cycles (84 weeks) in the absence of disease progression or unacceptable toxicity.

Evan J Lipson

This phase I trial studies how well tacrolimus, nivolumab, and ipilimumab work in treating kidney transplant recipients with cancer that cannot be removed by surgery (unresectable) or has spread to other places in the body (metastatic). Tacrolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving tacrolimus, nivolumab, and ipilimumab may work better in treating kidney transplant recipients with cancer compared to chemotherapy, surgery, radiation therapy, or targeted therapies.

PRIMARY OBJECTIVE:

I. To estimate the percent of kidney transplant recipients with selected advanced cancers for whom standard therapies would be insufficient who, 16 weeks after administration of prednisone, tacrolimus, and nivolumab, experience complete response (CR), partial response (PR), or stable disease (SD) without allograft loss.

SECONDARY OBJECTIVES:

I. To estimate the objective response rate (ORR), rate of allograft loss, and durations of progression-free survival (PFS) and overall survival (OS) in the study population.

II. To estimate the ORR and rate of allograft loss in patients who experience progressive disease (PD) after administration of nivolumab and 1) receive ipilimumab and nivolumab, or 2) decrease or discontinue immunosuppression.

EXPLORATORY OBJECTIVES:

I. To characterize correlates of the host immune response, possibly including, but not limited to:

Ia. Histopathological characteristics of allograft rejection/loss. Ib. Immunological changes in the tumor microenvironment (e.g., changes in T-cell subset populations or expression of immune checkpoint molecules) in paired biopsies obtained pre-treatment and on-treatment.

Ic. Changes in donor-derived cell-free deoxyribonucleic acid (DNA) (dd-cfDNA) as a marker for allograft rejection.

Id. Characteristics of anti-programmed death-1 (PD-1)-associated immune-mediated adverse reactions (IMAR) in this patient population treated with immunosuppression.

OUTLINE:

Patients receive tacrolimus orally (PO) twice daily (BID) and prednisone PO once daily (QD). Within 28 days, patients then receive nivolumab intravenously (IV) over 30 minutes on day 1. Cycles repeat every 4 weeks for up to 24 cycles (96 weeks) in the absence of disease progression or unacceptable toxicity.

Patients who experience progressive disease (PD) or patients who have experienced allograft loss at 16 weeks receive nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes on day 1. Patients also receive tacrolimus PO BID and prednisone PO QD. Cycles repeat every 3 weeks for 4 cycles (12 weeks) in the absence of disease progression or unacceptable toxicity. Starting 6 weeks later, patients receive nivolumab IV over 30 minutes every 4 weeks for up to 21 cycles (84 weeks) in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 90 days, every 8 weeks for year 1, every 12 weeks for year 2, every 16 weeks for year 3, then every 24 weeks for year 4. Patients with PD are followed up every 12 weeks for up to 5 years.

Tacrolimus, Nivolumab, and Ipilimumab in Treating Kidney Transplant Recipients With Selected Unresectable or Metastatic Cancers

Immune Checkpoint Blockade for Kidney Transplant Recipients With Selected Unresectable or Metastatic Cancers

NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page

Percentage of kidney transplant recipients who experienced complete response (CR), partial response (PR) or stable disease (SD) without allograft loss.

Number (and percentage) of patients with a complete response (CR) or partial response (PR) based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria after receiving at least one dose of nivolumab.

Number of subjects who experienced allograft loss after receiving at least one dose of nivolumab.

From the first dose of nivolumab to the date of the first documented tumor progression or death due to any cause, whichever occurs first.

The time from the participant's first dose of nivolumab to the date of death from any cause.

The number of participants with a CR or PR response after receiving ipilimumab, nivolumab, tacrolimus, and prednisone.

Number of patients who experienced allograft loss after receiving nivolumab, ipilimumab, tacrolimus, and prednisone.

Patients received low-dose tacrolimus (serum trough goal 2-5 ng/mL), prednisone 5mg by mouth once a day, and nivolumab 480mg by infusion every 4 weeks for up to 96 weeks in the absence of disease progression or unacceptable toxicity.

Nivolumab, Tacrolimus, and Prednisone

Patients received low-dose tacrolimus (serum trough goal 2-5 ng/mL), prednisone 5mg by mouth once a day, nivolumab 3 mg/kg by infusion and ipilimumab 1 mg/kg by infusion every 3 weeks for 4 doses followed by maintenance nivolumab 480mg by infusion every 4 weeks for up to 96 weeks in the absence of disease progression or unacceptable toxicity.

Ipilimumab, Nivolumab, Tacrolimus, and Prednisone

Patients received low-dose tacrolimus (serum trough goal 2-5 ng/mL), prednisone 5mg by mouth once a day, and nivolumab 480mg by infusion every 4 weeks for up to 96 weeks in the absence of disease progression or unacceptable toxicity.

Patients who experienced disease progression by the 16-week time point, could receive tacrolimus, prednisone, nivolumab 3 mg/kg IV + ipilimumab 1 mg/kg by infusion every 3 weeks for 4 doses followed by maintenance nivolumab 480mg by infusion every 4 weeks for up to 96 weeks in the absence of disease progression or unacceptable toxicity.

Treatment (Tacrolimus, Prednisone, Nivolumab, Ipilimumab)

Age, Categorical

United States

Region of Enrollment

Height

Weight

The second treatment period where participants received ipilimumab, nivolumab, tacrolimus, and prednisone was optional.

Grants Administrative Manager

Complete response (CR), partial response (PR) or stable disease (SD) without allograft loss

Progressive Disease (PD) without allograft loss

Patients received low-dose tacrolimus (serum trough goal 2-5 ng/mL), prednisone 5 mg by mouth once a day, and nivolumab 480 mg by infusion over 30 minutes on day 1. Cycles repeated every 4 weeks for up to 24 cycles (96 weeks) in the absence of disease progression or unacceptable toxicity.

Number (and Percentage) of Outcome Responses After Receiving Nivolumab, Tacrolimus, and Prednisone

Objective Response (CR or PR) Rate (ORR) After Receiving Nivolumab, Tacrolimus, and Prednisone

Rate of Allograft Loss After Receiving Nivolumab, Tacrolimus, and Prednisone

Duration of Progression-free Survival After Receiving Nivolumab, Tacrolimus, and Prednisone

Duration of Overall Survival After Receiving Nivolumab, Tacrolimus, and Prednisone

Patients received low-dose tacrolimus (serum trough goal 2-5 ng/mL), prednisone 5 mg every day, nivolumab 3 mg/kg by infusion and ipilimumab 1 mg/kg by infusion every 3 weeks for 4 doses followed by maintenance nivolumab 480mg by infusion every 4 weeks for up to 96 weeks in the absence of disease progression or unacceptable toxicity.

Two participants who completed the initial treatment period did not start the second, optional treatment period due to disease progression or death.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Testing the Addition of Radiation Therapy to Immunotherapy for Merkel Cell Carcinoma	NCT03304639	Advanced Merkel... Clinical Stage ... Clinical Stage ... Metastatic Merk... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag...	Pembrolizumab Stereotactic Bo...	18 Years -	National Cancer Institute (NCI)
Testing Pembrolizumab Versus Observation in Patients With Merkel Cell Carcinoma After Surgery, STAMP Trial	NCT03712605	Pathologic Stag... Pathologic Stag... Pathologic Stag...	Best Practice Biospecimen Col... Computed Tomogr... Magnetic Resona... Pembrolizumab Positron Emissi... Radiation Thera...	18 Years -	National Cancer Institute (NCI)
Testing the Addition of Radiation Therapy to Immunotherapy for Merkel Cell Carcinoma	NCT03304639	Advanced Merkel... Clinical Stage ... Clinical Stage ... Metastatic Merk... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag...	Pembrolizumab Stereotactic Bo...	18 Years -	National Cancer Institute (NCI)
Tacrolimus, Nivolumab, and Ipilimumab in Treating Kidney Transplant Recipients With Selected Unresectable or Metastatic Cancers	NCT03816332	Clinical Stage ... Clinical Stage ... Clinical Stage ... Clinical Stage ... Metastatic Basa... Metastatic Mela... Metastatic Merk... Metastatic Skin... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Unresectable Ba... Unresectable Me... Unresectable Me...	Ipilimumab Nivolumab Prednisone Tacrolimus	18 Years -	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for pathologic stage iii cutaneous merkel cell carcinoma ajcc v8