SAbR Plus Ipilimumab Plus Nivolumab in Metastatic Melanoma Patients

NCT03126461 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: STU 082016-058
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

A one-arm, single center phase 2 trial of SAbR plus ipilimumab plus nivolumab in advanced metastatic melanoma patients

Conditions

Melanoma; Metastatic Melanoma

Keywords

metastatic melanoma

Outcome Measures

Primary Outcomes (1)

• Change of tumor size from baseline to follow up

  treatment response rate-RR based on RECISTv1.1

  at 12, 24, 36 weeks

Secondary Outcomes (3)

• disease control rate

  at 12, 24, 36 weeks

• Number of treatment-related adverse events

  2 years

• programmed death ligand-1 (PD-L1) expression

  baseline, cycle 1 Day 1, and week 15

Study Arms (1)

SAbR plus ipilimumab plus nivolumab

EXPERIMENTAL

SAbR/GRID plus ipilimumab 3mg/kg IV q3wk x 4 plus nivolumab 1 mg/kg IV q3wk x 4, followed by nivolumab 240 mg IV q 2wk until progression or intolerable toxicity

Radiation: SAbR; Drug: Ipilimumab; Drug: Nivolumab

Interventions

SAbR RADIATION

For patients treated on the "GRID A" regimen, a dose of 15-20 Gy will be delivered with the GRID device in either a single field, with prescription to dmax, or with parallel opposed GRID fields (matching beamlets from the opposed directions). For patients treated on the "GRID B" regimen, this same dose will be delivered, with a subsequent regimen of 3 Gy X 10 fractions, with the first of these fractions following the GRID dose.

Also known as: Stereotactic ablative body radiation

SAbR plus ipilimumab plus nivolumab

Ipilimumab DRUG

ipilimumab 3mg/kg IV q3wk x 4

Also known as: Yervoy®

SAbR plus ipilimumab plus nivolumab

Nivolumab DRUG

nivolumab 1 mg/kg IV q3wk x 4

Also known as: Opdivo®

SAbR plus ipilimumab plus nivolumab

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologic diagnosis of metastatic melanoma.
• Any number of prior systemic therapeutic regimens including chemotherapy, pathway inhibitors, biochemotherapy, investigational agents, and immunotherapies other than ipilimumab, nivolumab or other CTLA-4, PD-1 or PD-L1 inhibitors.
• Patients must have measurable disease in at least 2 non-radiated sites as defined by RECIST v1.1. All sites must be evaluated within 4 weeks prior to registration.
• Age ≥ 18 years.
• Eligible for SABR to 1-5 sites of disease (Refer to 3.2.10)
• Performance status ECOG 0-2.
• Adequate organ and marrow function as defined below:
• leukocytes ≥ 1,000/mcL
• absolute neutrophil count ≥ 1,000/mcL
• platelets ≥ 75,000/mcl
• total bilirubin \< 2.5X institutional upper limit of normal or
• in subjects with Gilbert's Syndrome
• AST(SGOT)/ALT(SPGT) ≤ 4 X institutional upper limit of normal
• creatinine \< 4X institutional upper limit of normal
• hemoglobin \>7g/dL

You may not qualify if:

• No concomitant therapy with any of the following: IL2, interferon, or other non-study immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive agents; or other investigational therapies; all such therapies must have been discontinued \>4weeks prior to registration.
• No infection with HIV and no known history of hepatitis B or hepatitis C virus indicating acute or chronic infection or active TB.
• Patients are excluded if they have a history of any other malignancy from which the patient has been disease-free for less than 2 years, with the exception of adequately treated (Surgery or radiation) and cured basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix, or localized adenocarcinoma of the cervix.
• 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.
• Patients must not be pregnant or nursing.
• Patients are excluded if they have a history of prior treatment with ipilimumab, CTLA-4 inhibitor or agonist, nivolumab, PD-1 or PD-L1 inhibitor.
• Subjects who have had major surgery within 2 weeks prior to first dose of drug
• Subjects who have had radiation therapy within 2 weeks prior to first dose of drug
• Uncontrolled adrenal insufficiency or active chronic liver disease
• Any history of CNS metastases that is not adequately treated (surgery or radiation ) \>14 days prior to registration.
• Any active known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
• Any condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days prior to the first dose of study drug. Inhaled steroids and adrenal replacement steroid doses up to 10 mg daily prednisone equivalent are permitted (although not encouraged) in the absence of active autoimmune disease.
• Subjects with life expectancy \< 6 months
• Subjects receiving any other investigational or standard antineoplastic agents.

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead

Study Sites (1)

University of Texas Southwestern Medical Center - Dallas

Dallas, Texas, 75390, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

Ipilimumab; Nivolumab

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Kevin Albuquerque, MD

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 23, 2017
• First Posted: April 24, 2017
• Study Start: March 1, 2018
• Primary Completion: December 31, 2022
• Study Completion: December 31, 2022
• Last Updated: August 20, 2020

Record last verified: 2018-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)