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Radiation and Combination Immunotherapy for Melanoma

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ClinicalTrials.gov Identifier: NCT03850691
Recruitment Status : Suspended (amendment pending)
First Posted : February 22, 2019
Last Update Posted : February 3, 2021
Sponsor:
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota

Brief Summary:
This is a Phase 2 study designed to evaluate the combination of checkpoint blockade and aldesleukin (IL-2) therapy after a course of standard of care palliative radiation in the management of unresectable metastatic melanoma. To be eligible, a patient must have a minimum of 3 (preferably >5) radiographically distinct, measurable (>1.5 cm) lesions based on RECIST 1.1. Metastatic cutaneous melanoma must be refractory to standard immunotherapy drugs, molecular targeted agents and/or chemotherapy. Patients with ocular melanoma subtypes may enroll in this study without prior therapy, as there is no standard front-line therapy for this subset of patients.

Condition or disease Intervention/treatment Phase
Metastatic Melanoma Drug: Aldesleukin: All Patients Drug: Nivolumab: Cohort 1 (Cutaneous) Drug: Nivolumab: Cohort 2 (Ocular) Drug: Ipilimumab: Cohort 2 (Ocular) Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 44 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Study of Palliative Radiation and Combination Sequential Immunotherapy for Metastatic Cutaneous Melanoma and Ocular Melanoma
Actual Study Start Date : May 28, 2019
Estimated Primary Completion Date : December 2025
Estimated Study Completion Date : December 2025

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Melanoma
MedlinePlus related topics: Melanoma
Drug Information available for: Nivolumab

Arm Intervention/treatment
Experimental: Cohort 1: Nivolumab Drug: Aldesleukin: All Patients

Cycle 1:

(600,000 U/kg/dose) given as a bolus infusion once every 8 to 12 hours over 5 days or until no longer tolerated (to a maximum of 10 doses). Administered as an inpatient.

Days 1-5 and Days 15-19 (all patients)

Other Name: IL-2

Drug: Nivolumab: Cohort 1 (Cutaneous)

Cycle 1: 6 Week Duration Nivolumab 240 mg IV

Cycle 2: 6 Week Duration Nivolumab 240 mg IV on Day 1, 15 and 29

Cycle 3: 4 Week Duration Nivolumab 240 mg IV on Day 1 and 15

Patients may continue maintenance nivolumab 240 mg IV every 2 weeks OR nivolumab 480 mg IV every 4 weeks per 2018 FDA approval at discretion of the treating physician and independent of this study


Experimental: Cohort 2: Nivolumab & Ipilimumab Drug: Aldesleukin: All Patients

Cycle 1:

(600,000 U/kg/dose) given as a bolus infusion once every 8 to 12 hours over 5 days or until no longer tolerated (to a maximum of 10 doses). Administered as an inpatient.

Days 1-5 and Days 15-19 (all patients)

Other Name: IL-2

Drug: Nivolumab: Cohort 2 (Ocular)

Cycle 1: 6 Week Duration Nivolumab 3 mg/kg IV on Day 29

OR for a high risk patient with an excellent performance status, the following regimen may be given at the discretion of the treating investigator:

Nivolumab 1 mg/kg IV on Day 29

Cycle 2: 6 Week Duration Nivolumab on Day 8 and on Day 29 using the same dose regimen as used Cycle 1 Day 29

Cycle 3: 4 Week Duration Nivolumab on Day 8 using the same dose regimen as used Cycle 1 Day 29.

Patients may continue maintenance nivolumab 240 mg IV every 2 weeks OR nivolumab 480 mg IV every 4 weeks per 2018 FDA approval at discretion of the treating physician and independent of this study


Drug: Ipilimumab: Cohort 2 (Ocular)

Cycle 1: 6 Week Duration Ipilimumab 1 mg/kg IV on Day 29

OR for a high risk patient with an excellent performance status, the following regimen may be given at the discretion of the treating investigator:

Ipilimumab 3 mg/kg IV on Day 29

Cycle 2: 6 Week Duration Ipilimumab on Day 8 and on Day 29 using the same dose regimen as used Cycle 1 Day 29

Cycle 3: 4 Week Duration Ipilimumab on Day 8 using the same dose regimen as used Cycle 1 Day 29





Primary Outcome Measures :
  1. Objective Response Rate (ORR) [ Time Frame: 2 Year ]
    Proportion of patients who achieved complete response (CR) or partial response (PR).

  2. Safety and Tolerability of Sequential Combination Immunotherapy (Incidence of adverse events) [ Time Frame: 2 Year ]
    Incidence of adverse events

  3. Safety and Tolerability of Sequential Combination Immunotherapy (Incidence of stopping rule events) [ Time Frame: 2 Year ]
    Incidence of stopping rule events


Secondary Outcome Measures :
  1. Progression-Free Survival (PFS) [ Time Frame: 6 Month ]
    Based on RECIST 1.1 criteria

  2. Overall Survival (OS) [ Time Frame: 12 Month ]
    Incidence of survival



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Biopsy-proven unresectable, metastatic melanoma refractory to standard immunotherapy drugs or regimens, including prior treatment with Aldesleukin (IL-2), GM-CSF, Ipilimumab, Nivolumab, Pembrolizumab, and/or Imlygic (T- VEC).

    • Prior clinical trial participation or treatment with molecularly targeted agents (i.e. Vemurafenib/Cobimetinib, Dabrafenib/Trametinib) or chemotherapy (i.e. Temozolomide, Dacarbazine, Platinum, or Taxanes) is permitted.
    • Patients with ocular melanoma may enroll (Cohort 2) without prior therapy as there is no standard 1st line therapy for this subset of melanoma.
  • Must have a minimum of 3 radiographically distinct (>1.5 cm) lesions measurable by RECIST 1.1 at time of study enrollment (>5 preferred).

    • A maximum of 2 metastases per treated organ may be targeted for palliative radiation, but must be separated by more than 5 cm of normal tissue
    • At least 2 non-irradiated lesions are required for systemic response assessments
  • Pulmonary metastases: Pulmonary metastasis permissible. Appropriate candidates with lung lesions may be considered for ablative hypofractionation using SBRT.
  • Hepatic metastases: Hepatic metastasis permissible. Appropriate candidates with metastasis to liver may be considered for ablative hypofractionation using SBRT .
  • Brain metastases: Brain metastases may be treated using Gamma Knife Radiosurgery (GKR) or whole brain radiation therapy (WBRT) per the treating radiation oncologist. Total radiation dose and number of fractions will be determined by the treating radiation oncologist based on anatomic and dosing constraints. MRI of the vertebral column is required for all patients with suspected epidural tumor extension.
  • Must have sufficient archival tissue block material (1.5 x 1.5 x 1.5 cm) and/or newly obtained core or excisional biopsy of tumor tissue; minimum of 2 cores.
  • ECOG performance status 0 or 1 (Appendix 2)
  • Age 18 through 80 years of age; > 80 years of age must be approved by Principal Investigator.
  • Adequate organ function within 14 days of enrollment (30 days for pulmonary and cardiac assessments) defined as:

    • Hematologic: leukocytes ≥ 2,000/mcL, ANC ≥ 1,000/mcL, hemoglobin ≥ 9.0 g/dL, platelets ≥ 100,000/mcL unsupported by transfusions
    • Renal: Serum creatinine ≤ 1.8 mg/dL; for patients with a creatinine > 1.5 mg/dL or a history of renal dysfunction, an estimated glomerular filtration rate ≥ 35 mL/min/1.73 m2 is required
    • Hepatic: AST, ALT, and alkaline phosphatase ≤ 5 x upper limit of normal and total bilirubin ≤ 2.0 mg/dL
    • Pulmonary: oxygen saturation ≥90% on room air; corrected DLCO and FEV1, ≥ 60% predicted
    • Cardiac: Absence of clinical decompensated congestive heart failure or uncontrolled arrhythmia; left ventricular ejection fraction (echocardiogram within 6 months permitted) ≥ 40%. QTc must be < 450 ms in males and < 470 ms in females.
  • A minimum of 1 week between last anti-tumor treatment if given, and 1st dose of radiation therapy (not applicable for patients enrolling after palliative radiation therapy).
  • Recovery from previous cancer treatment if applicable defined as ≤ Grade 1 (by CTCAE 5.0 criteria) at enrollment
  • Women of childbearing potential and males with partners of childbearing potential must agree to the use of barrier methods of contraception, hormonal contraceptives, or abstain from heterosexual activity for the duration of study treatment and for 3 months after the last dose of study drug.
  • Ability to understand and provide voluntary written consent

Exclusion Criteria:

  • Pregnant or breast feeding. The agents used in this study have the potential to harm a fetus. Radiation is a known teratogen. There is insufficient information regarding potential for fetal harm during immunotherapy at this time. Biological females of childbearing potential must have a negative pregnancy test within 14 days of enrollment.
  • Concurrent use of high dose steroids; chronic steroid use of < 2 mg dexamethasone or equivalent per day is permissible
  • Concurrent malignancy requiring active treatment, except basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ
  • Severe and active autoimmune diseases requiring systemic immunosuppression
  • Prior organ allograft or allogeneic transplantation
  • Other contraindication to IL-2, nivolumab, ipilimumab, or combination immunotherapy per treating medical oncologist
  • Live vaccines within 30 days prior to the first dose of IL-2 and while participating in the trial. Examples of live vaccines include, but are not limited to, measles, mumps, rubella, chicken pox, yellow fever, rabies, BCG, and typhoid (oral) vaccine. Seasonal influenza vaccines for injection are generally inactivated virus vaccines and are allowed. Intranasal influenza vaccine (eg, Flu - Mist®) is a live attenuated vaccine, and is not allowed.

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): NCT03850691


Locations
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United States, Minnesota
University of Minnesota Masonic Cancer Center
Burnsville, Minnesota, United States, 55337
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
Investigators
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Principal Investigator: Evidio Domingo-Musibay, MD Division of Hematology, Oncology and Transplantation, University of Minnesota
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Responsible Party: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT03850691    
Other Study ID Numbers: 2018LS110
First Posted: February 22, 2019    Key Record Dates
Last Update Posted: February 3, 2021
Last Verified: February 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Masonic Cancer Center, University of Minnesota:
MM
Additional relevant MeSH terms:
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Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Aldesleukin
Nivolumab
Ipilimumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents