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Phase II Trial of Combination Anti-PD-1 and Aldesleukin for Metastatic Melanoma and Renal Cell Carcinoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05155033
Recruitment Status : Recruiting
First Posted : December 13, 2021
Last Update Posted : January 25, 2023
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

Brief Summary:

Background:

Aldesleukin is used to treat metastatic or advanced melanoma and renal cell carcinoma. Pembrolizumab is used to treat many cancers including melanoma. Researchers want to see if these drugs can be used together to produce better results in people with these types of cancer.

Objective:

To learn if the combination of pembrolizumab and aldesleukin can be used to treat metastatic or advanced melanoma and renal cell cancer.

Eligibility:

Adults aged 18 years or older who have metastatic or advanced melanoma or renal cell carcinoma.

Design:

Participants will be screened with:

  • Medical history
  • Physical exam
  • Electrocardiogram
  • Blood and urine tests
  • Ability to perform tasks of daily living
  • Imaging scans (CT, MRI, PET, and/or X-rays). They may get a contrast agent to enhance the images.
  • Photographs, if needed

Some of these tests will be repeated during the study.

Participants will receive the study drugs by IV (a plastic tube that is put into a vein) for 4 days. A second cycle of treatment will be given 21 days later. They will stay in the hospital for each of the cycles in the first course of treatment. After 2 months, their cancer will be evaluated. They may receive a second course of pembrolizumab alone on Days 1 and 21. They will not have to stay in the hospital for this course.

About 30 days after treatment ends, participants will have a safety follow-up visit. Then they will have visits every 3 months for up to 1 year, and then every 6 months for up to 4 years. Follow-up can also be done by phone, email, and mail. If their cancer gets worse, they will stop having visits.

Participation will last for 5 years.


Condition or disease Intervention/treatment Phase
Metastatic Melanoma Advanced Locoregional Melanoma Metastatic Renal Cell Carcinoma Clear Cell Histology Drug: Pembrolizumab Drug: Aldesleukin Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 78 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Trial of Combination Anti-PD-1 and Aldesleukin for Metastatic Melanoma and Renal Cell Carcinoma
Actual Study Start Date : August 18, 2022
Estimated Primary Completion Date : September 1, 2024
Estimated Study Completion Date : September 1, 2025


Arm Intervention/treatment
Experimental: 1 - Pembro and IL-2
Course 1: pembrolizumab (200 mg IV) on Day 1 of each cycle with aldesleukin (600,000 IU/kg intravenous bolus every eight hours) continuing for up to 4 days (maximum 10 doses) for 2 cycles (each 21 days). Course 2: pembrolizumab (200 mg IV) on Day 1 of each cycle for 2 cycles (each 21 days).
Drug: Pembrolizumab
Pembrolizumab 200 mg IV over approximately 30 minutes on Day 1 of cycles 1 and 2 during Courses 1 and 2.

Drug: Aldesleukin
Aldesleukin (IL-2) administration [600,000 IU/kg IV bolus every 8 hours continuing for up to 4 days (maximum 10 doses)] starting on Day 1 of cycles 1 and 2 during Course 1.




Primary Outcome Measures :
  1. Response rate in treatment refractory disease [ Time Frame: 8 weeks after Course 1 Cycle 1 then after Course 2, every 3 months x 3 (up to one year), every 6 months x 8 (up to five years) ]
    Determine the rate of objective response (using RECIST v1.1 criteria)


Secondary Outcome Measures :
  1. Progression Free Survival [ Time Frame: Every 2-6 months for up to 5 years ]
    Elapsed duration from enrollment to progression of disease

  2. Response rate in treatment naive melanoma [ Time Frame: 8 weeks after Course 1 Cycle 1 then after Course 2, every 3 months x 3 (up to one year), every 6 months x 8 (up to five years) ]
    Determine the rate of objective response (using RECIST v1.1 criteria)

  3. Safety and tolerance [ Time Frame: First dose through 30 days after last treatment ]
    Using standard CTCAE 5.0



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:
  • Participants must have histologically or cytologically confirmed cancer that falls into one of three cohorts: (1) metastatic melanoma or advanced locoregional melanoma not amenable to curative surgical resection and refractory to anti-PD-1 therapy; (2) metastatic renal cell carcinoma (clear cell histology) refractory to at least one line of PD1/PDL1 based therapy; (3) metastatic or advanced locoregional melanoma not amenable to curative surgical resection and naive to anti-PD-1 therapy.
  • Participants must have measurable disease (per RECIST v1.1 criteria), metastatic melanoma or renal cell cancer.
  • Age >=18 years of age.
  • Clinical performance status of ECOG 0 or 1.
  • Willing to practice birth control from the time of enrollment on this study and for four months after treatment.
  • Must have a negative pregnancy test because of the potentially dangerous effects of the treatment on the fetus.
  • Seronegative for HIV antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Participants who are HIV seropositive may have decreased immune-competence and thus be less responsive to the experimental treatment and more susceptible to its toxicities.)
  • Seronegative for hepatitis B antigen and for hepatitis C antibody. If hepatitis C antibody test is positive, then participant must be tested for the presence of antigen by RT-PCR and be HCV RNA negative.
  • Participants must have adequate organ and marrow function as defined below:

    • ANC > 1000/mm^3 without the support of filgrastim
    • WBC >= 3000/mm^3
    • Platelet count >= 100,000/mm^3
    • Hemoglobin > 8.0 g/d (Subject may be transfused to reach this cut-off)
    • Serum ALT/AST <= 5.0 x ULN
    • Serum creatinine <= 1.6 mg/dL
    • Total bilirubin <= 2.0 mg/dL, except in participants with Gilbert s Syndrome, who must have a total bilirubin < 3.0 mg/dL.
  • More than four weeks must have elapsed since completion of any prior systemic therapy at the time of enrollment.

Note: Participant may have undergone minor surgical procedures or limited field radiotherapy within the four weeks prior to enrollment, as long as related major organ toxicities have recovered to <= grade 1.

  • Ability of subject to understand and the willingness to sign a written informed consent document.
  • Willing to sign a Durable Power of Attorney Form.
  • Subject must be co-enrolled on protocol 03-C-0277

EXCLUSION CRITERIA:

  • Participant is breastfeeding because of the potentially dangerous effects of the treatment on the fetus or infant.
  • Concurrent systemic steroid therapy.
  • Active systemic infections requiring anti-infective treatment, coagulation disorders, or any other active or uncompensated major medical illnesses.
  • Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease and AIDS).
  • History of major organ autoimmune disease.
  • Grade 3 or 4 major organ irAEs following treatment with anti-PD-1/PD-L1 monotherapy, including but not limited to myocarditis, pneumonitis, colitis, and hepatotoxicity.
  • Concurrent opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Participants who have decreased immune-competence may be less responsive to the experimental treatment and more susceptible to its toxicities.)
  • History of severe immediate hypersensitivity reaction to pembrolizumab or aldesleukin.
  • History of coronary revascularization or ischemic symptoms.
  • For select participants with a clinical history prompting cardiac evaluation: last known LVEF <= 45%.
  • For select participants with a clinical history prompting pulmonary evaluation: known FEV1 <= 50%.
  • Participant is receiving any other investigational agents.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05155033


Contacts
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Contact: NCI SB Immunotherapy Recruitment Center (866) 820-4505 irc@nih.gov
Contact: Stephanie L Goff, M.D. (240) 760-6214 stephanie.goff@nih.gov

Locations
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United States, Maryland
National Institutes of Health Clinical Center Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact NCI/Surgery Branch Recruitment Center    866-820-4505    irc@nih.gov   
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Stephanie L Goff, M.D. National Cancer Institute (NCI)
Additional Information:
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Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT05155033    
Other Study ID Numbers: 10000354
000354-C
First Posted: December 13, 2021    Key Record Dates
Last Update Posted: January 25, 2023
Last Verified: January 18, 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: .All IPD recorded in the medical record will be shared with intramural investigators upon request. @@@@@@All collected IPD will be shared with collaborators under the terms of collaborative agreements
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Time Frame: Clinical data will be available during the study and indefinitely.
Access Criteria: Clinical data will be made available via subscription to BTRIS and with the permission of the study PI.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ):
Immunotherapy
Monoclonal Antibody
Additional relevant MeSH terms:
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Carcinoma
Melanoma
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Nevi and Melanomas
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Aldesleukin
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents