Radiation Therapy With Combination Immunotherapy for Relapsed/Refractory Metastatic Melanoma

NCT03297463 | Withdrawn Phase 1 FDA Drug

• 1 other identifier: 2016LS172
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 1b/2 study designed to evaluate combination of the human T-cell cytokine Interleukin-2 (IL-2) and a checkpoint inhibitor Ipilimumab immediately following a course of hypofractionated palliative radiation therapy in the management of unresectable, relapsed/refractory metastatic melanoma.

Conditions

Metastatic Melanoma; Pulmonary Metastases; Hepatic Metastases; Brain Metastases

Outcome Measures

Primary Outcomes (5)

• Phase 1: Maximum Tolerated Dose (MTD)

  Incidence of Adverse Events

  Cycle 2 Day 1

• Phase 1: Maximum Tolerated Dose (MTD)

  Incidence of Adverse Events

  Cycle 2 Day 15

• Phase 1: Maximum Tolerated Dose (MTD)

  Incidence of Adverse Events

  30 days after last IL-2

• Phase 2: Objective Response Rate (ORR)

  Disease re-assessment includes physical examination, as well as radiographic response assessment (RECIST v1.1) of non-irradiated target lesions using CT (or PET/CT) and/or at MRI.

  Day 35

• Phase 2: Objective Response Rate (ORR)

  Disease re-assessment includes physical examination, as well as radiographic response assessment (RECIST v1.1) of non-irradiated target lesions using CT (or PET/CT) and/or at MRI.

  30 days after last IL-2

Secondary Outcomes (2)

• Progression-free survival (PFS)

  Every 3 Months until 2 Years from 1st IL-2 Dose

• Overall survival (OS)

  Every 3 Months until 2 Years from 1st IL-2 Dose

Study Arms (2)

Phase Ib (Dose Escalation)

EXPERIMENTAL

Drug: Interleukin-2 & Ipilimumab (P-Ib)

Phase II (Dose Expansion)

EXPERIMENTAL

Drug: Interleukin-2 & Ipilimumab (P-II)

Interventions

Interleukin-2 & Ipilimumab (P-Ib) DRUG

Phase Ib: \- Ipilimumab will be administered in a 3 + 3 dose escalation design. * The starting dose will be 0.3 mg/kg administered within 7 days of day 1 cycle 2 ALdesleukin (IL-2). * If dose limiting autoimmune toxicities (DLTs) are not observed, the next cohort will receive 1.5 mg/kg. * The final cohort will receive 3 mg/kg, in the event that cohort 2 does not exhibit DLTs. * In the event of excessive toxicity in cohort 1, then a -1 dose level of 0.1 mg/kg may be evaluated in subsequent cohorts. Cohort sizes will increase to 6 patients if 1 of 3 patients in a cohort experience a DLT. * Once the maximum tolerated dose/recommended phase 2 dose (MTD/RP2D) is declared, no staggering of enrollment is required for accrual.

Also known as: IL-2, Yervoy

Phase Ib (Dose Escalation)

Interleukin-2 & Ipilimumab (P-II) DRUG

Phase II: \- Interleukin-2 \& Ipilimumab will be administered at the maximum tolerated dose/recommended phase 2 dose (MTD/RP2D).

Also known as: IL-2, Yervoy

Phase II (Dose Expansion)

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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 HD-XRT, 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 to 85 years of age; \> 85 years of age must be approved by Principal Investigator.
• Adequate organ function within 14 days of registration (30 days for pulmonary and cardiac assessments) defined as:
• Hematologic: Leukocytes ≥ 3,000/mcL, ANC ≥ 1,000/mcL, Hemoglobin ≥ 9.0 g/dL, Platelets ≥ 120,000/mcL
• 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 ≤ 10 x upper limit of normal and total bilirubin ≤ 2.0 mg/dL Pulmonary: oxygen saturation ≥90% on room air; corrected DLCO and FEV1, ≥ 50% predicted

You may not qualify if:

• 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 serum pregnancy test within 14 days of registration.
• Diagnosis of immunodeficiency
• 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
• Prior organ allograft or allogeneic transplantation
• Autoimmune disease
• Uncontrolled intercurrent or psychiatric illness or social situation that would limit compliance with study requirements
• 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 killed virus vaccines and are allowed. However, intranasal influenza vaccines (eg, Flu - Mist®) are live attenuated vaccines, and are not allowed.

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota: lead

Study Sites (1)

Masonic Cancer Center - University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

MeSH Terms

Conditions

Melanoma; Brain Neoplasms

Interventions

Interleukin-2; Ipilimumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins

Study Officials

• Domingo-Musibay Evidio, MD

  Masonic Cancer Center, University of Minnesota

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 26, 2017
• First Posted: September 29, 2017
• Study Start: January 31, 2018
• Primary Completion: February 1, 2020
• Study Completion: February 1, 2020
• Last Updated: August 1, 2018

Record last verified: 2018-07

Locations

US (1)