SBRT as a Vaccination for Metastatic Melanoma

NCT04042506 | Withdrawn Phase 2 FDA Drug

• 2 other identifiers: J18145IRB00188445
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

Brief Summary

Immunotherapy with PD-1 blockade is a first-line treatment for patients with advanced melanoma, but unfortunately most patients progress on this therapy. Recent evidence suggests that radiation can enhance the immune response in the presence of checkpoint blockade. The investigators aim to determine if radiation can elicit increased immune responses in patients who have stable or progressive disease on nivolumab.

Conditions

Metastatic Melanoma

Keywords

immune checkpoint blockade; SBRT; Nivolumab

Outcome Measures

Primary Outcomes (1)

• Safety of SBRT in the presence of immune checkpoint blockade (ICB) as measured by number of participants experiencing adverse events

  Number of participants with advanced unresectable melanoma, receiving SBRT in the presence of ICB who experience metabolic or hematological, or non-hematological adverse events Grade 3 or higher, as defined by CTCAE v4.0

  12 weeks

Secondary Outcomes (1)

• Clinical abscopal effect as assessed by number of unradiated lesions with response per RECIST 1.1.

  12 weeks

Study Arms (1)

Extracranial SBRT and Nivolumab

EXPERIMENTAL

Stereotactic body radiation therapy (SBRT) will be given to a single extracranial metastatic site in combination with nivolumab. Patients will receive nivolumab 480mg intravenously (IV) every 4 weeks (1 cycle = 8 weeks), as well as SBRT dose of 8-10 Gy x 3 fractions (at maximum 3 doses per week) delivered to 1 extracranial site between days 1-14 of Cycle 1. Nivolumab will be continued until confirmed progression, unacceptable toxicity, or total of 6 Cycles (whichever occurs first).

Drug: Nivolumab 10 MG/ML Intravenous Solution [OPDIVO]; Radiation: Stereotactic Body Radiation Therapy (SBRT)

Interventions

Nivolumab 10 MG/ML Intravenous Solution [OPDIVO] DRUG

480mg IV every 4 weeks

Also known as: Opdivo

Extracranial SBRT and Nivolumab

Stereotactic Body Radiation Therapy (SBRT) RADIATION

SBRT dose of 8-10 Gy x 3 fractions (at maximum 3 doses per week) delivered to 1 extracranial site between days 1-14 of Cycle 1.

Extracranial SBRT and Nivolumab

Eligibility Criteria

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

You may qualify if:

• Signed Written Informed Consent
• Willing and able to provide informed consent
• Age ≥ 18 years
• Target Population
• Histological confirmation of melanoma
• Advanced unresectable (AJCC Stage III or IV) disease (cutaneous, mucosal, acral or ocular)
• Stable disease or progression (RECIST 1.1) after anti-PD-1 monotherapy (≥ 16 weeks and ≥ 2 CT assessments). The maximum time period off anti-PD-1 monotherapy, prior to protocol therapy, cannot exceed 2 months.
• Prior systemic treatment regimen in the advanced/metastatic setting is allowed (BRAF inhibitor, chemotherapy, cytokine/biologic therapy or clinical trial)
• Prior treatment with anti-CTLA-4 checkpoint inhibitor is allowed
• Minimum of 2 or more measurable lesions by RECIST 1.1, with at least 1 lesion accessible for clinical, US, or CT-guided needle biopsy. If 2 lesions, then one of those must measure 4cm in maximum diameter and be amenable for biopsy; this lesion will be utilized for abscopal effect determination as well. Otherwise, if 3 or more lesions are present, one lesion will receive SBRT, 2nd lesion will be used for radiographic abscopal response assessment, and 3rd lesion will be used for pre- and post-treatment biopsies.
• ECOG Performance Status of 0-1

You may not qualify if:

• Target Disease Exceptions
• Prior radiation within 6 months of enrollment (excluding brain metastases), or at any time to one of the 3 lesions for treatment/assessment
• If patient has \>1 lesion which requires immediate/urgent management with RT due to present or impending clinical consequences (uncontrolled pain, risk of loss of function), such a patient will not be enrolled on this trial
• Medical History and Concurrent Diseases
• Major toxicity from prior anti-PD-1 which precludes continuation of anti-PD-1 therapy.
• Pregnancy or inability to use contraception (if childbearing age)
• Any active or recent history of a known or suspected autoimmune disease or recent history of a syndrome that required systemic corticosteroids (\> 10 mg daily prednisone equivalent) or immunosuppressive medications except for syndromes which would not be expected to recur in the absence of an external trigger. Subjects with vitiligo or type I diabetes mellitus or residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement are permitted to enroll. Patients with psoriasis not requiring active, systemic treatment are allowed.
• Any condition requiring systemic treatment with corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days prior to first dose of study drug. Inhaled steroids and adrenal replacement steroid doses up to 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
• Uncontrolled adrenal insufficiency
• Requirement for anti-coagulation with Coumadin, low molecular weight heparin and anti-thrombin inhibitors will be accepted if anticoagulation has been stable for at least 4 weeks and no recent history of prior bleeding complications.
• Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix, breast or low risk Gleason 6 prostate cancer
• Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS); Any positive test for hepatitis B or hepatitis C virus indicating acute or chronic infection
• Known medical condition (e.g., a condition associated with diarrhea or acute diverticulitis) that, in the investigator's opinion, would increase the risk associated with study participation or study drug administration or interfere with the interpretation of safety results
• Major surgery (i.e., nephrectomy) less than 28 days prior to the first dose of study drug
• Anti-cancer therapy less than 14 days prior to the first dose of study drug or palliative, focal radiation therapy less than 14 days prior to the first dose of study drug

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• Bristol-Myers Squibb: collaborator

Study Sites (2)

Johns Hopkins Bayview

Baltimore, Maryland, 21224, United States

Location

The Sidney Kimmel Comprehensive Cancer Center at The Johns Hopkins University

Baltimore, Maryland, 21231, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

Nivolumab; Radiosurgery

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; Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Daniel Song, MD

  Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a single-institution, single-arm phase II study. SBRT will be given to a single extracranial metastatic site in combination with nivolumab.

Study Record Dates

• First Submitted: July 31, 2019
• First Posted: August 2, 2019
• Study Start: November 26, 2019
• Primary Completion: November 26, 2019
• Study Completion: January 26, 2021
• Last Updated: April 12, 2021

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)