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Metastatic MelanomaPhase 2NCT04042506

SBRT as a Vaccination for Metastatic Melanoma

A Phase 2 study testing Nivolumab 10 MG/ML Intravenous Solution [OPDIVO] and Stereotactic Body Radiation Therapy (SBRT) in people with Metastatic Melanoma, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 2 sites in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Melanoma
What is being tested?
Nivolumab 10 MG/ML Intravenous Solution [OPDIVO] and Stereotactic Body Radiation Therapy (SBRT)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
2 sitesUnited States
Study dates
26 Nov 2019to 26 Jan 2021
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
Show all 11Show fewer
  • 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

Who cannot join

  • 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)
Show all 28Show fewer
  • 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
  • Presence of any toxicities attributed to prior immunotherapy, other than alopecia, that have not resolved to Grade 1 (NCI CTCAE v4) or baseline before administration of study drug
  • Physical and Laboratory Test Findings: Any of the following laboratory test findings:
  • WBC < 2,000/mm3
  • Neutrophils < 1,500/mm3
  • Platelets < 100,000/mm3
  • AST or ALT > 3 x ULN (> 5 x ULN if liver metastases are present)
  • Total Bilirubin > 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL)
  • Serum creatinine > 1.5 x upper limit of normal (ULN) or creatinine clearance < 40 mL/min (measured or calculated by Cockroft-Gault formula)
  • Allergies and Adverse Drug Reaction: History of severe hypersensitivity reaction to any monoclonal antibody or study drug components
  • Other Exclusion Criteria
  • Prisoners or subject who are involuntarily incarcerated
  • Not suitable for SBRT treatment
  • Subjects who are compulsorily detained for treatment of either a psychiatric or physical illness

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Johns Hopkins Bayview

    Baltimore, Maryland, 21224

  • The Sidney Kimmel Comprehensive Cancer Center at The Johns Hopkins University

    Baltimore, Maryland, 21231

Other trials in United States

About this study

Official title: In Situ Vaccination With Stereotactic Body Radiation Therapy (SBRT) as a Strategy to Overcome Resistance to Immune Checkpoint Blockade: a Phase II Clinical Trial of SBRT and Anti-PD-1 Therapy With Immunologic Correlates

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.

Read the detailed description

To determine safety of stereotactic body radiation therapy (SBRT) in presence of ICB in patients with advanced unresectable melanoma. Toxicity will be deemed acceptable if the rate of Grade 3+ adverse events (CTC v4) is ≤ 33%, with relevant AEs defined as either of the following occurring between the start of SBRT and 12 weeks following SBRT completion:

  • Any grade 3-5 metabolic or hematological toxicity that is related, probably related or possibly related to nivolumab or SBRT.
  • Any grade 3-5 non-hematological toxicity that is related, probably related or possibly related to SBRT.

Secondary Endpoints:

  • To determine whether SBRT results in a clinical abscopal effect on unirradiated lesions. The hypothesized rate of abscopal effect is >14%.

Exploratory Correlative studies:

  • In select patients for whom TCRseq reveals clonal expansion in non-irradiated tumor and serial blood specimens, the relevance of such expansion to tumor-specific responses will be investigated using mutation-associated neoantigens (MANAFEST) assays.
  • Serial stool specimens will be studied to correlate potential changes in microbiome with abscopal effect.
  • To determine whether SBRT promotes clonal expansion of melanoma-specific T-cells, in both peripheral blood and within TME of non-irradiated lesions.
  • To determine whether TCR clonal expansion correlates with clinically observed abscopal response.
  • To identify additional immunological biomarkers in the non-irradiated (abscopal) TME using intratumoral gene expression profiling to assess for induction and upregulation of a Type I IFN signature among responders1-3. IHC in TME will be used to characterize modulation of immune cell populations pre- and post-SBRT, and to assess correlation of PD-L1 and other immune-checkpoint receptor expression with responsiveness to SBRT and changes in TME post-SBRT.
Being tested
Nivolumab 10 MG/ML Intravenous Solution [OPDIVO], Stereotactic Body Radiation Therapy (SBRT)
Keywords
immune checkpoint blockade, SBRT, Nivolumab
Medical subject headings
Melanoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Nivolumab 10 MG/ML Intravenous Solution [OPDIVO]Drug

    Also called Opdivo

    480mg IV every 4 weeks

  • 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.

Study groups in NCT04042506
Study groupRoleWhat they receive
Extracranial SBRT and NivolumabExperimentalStereotactic 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).
Receives: Drug: Nivolumab 10 MG/ML Intravenous Solution [OPDIVO]; Radiation: Stereotactic Body Radiation Therapy (SBRT)

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 12 weeks

Secondary outcomes (1)

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

    Number of lesions that are not targeted by SBRT with any response as defined by RECIST 1.1 criteria. Complete response (CR) = disappearance of all target lesions and normalization of tumor marker levels; Partial response (PR) = decrease from baseline >= 30% in the sum of the longest diameter of all target lesions.

    Measured: 12 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Aug 2019
  2. Study start26 Nov 2019
  3. Primary completion26 Nov 2019
  4. Study completion26 Jan 2021

Why it stopped: Unable to enroll patients in this study

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
This is a single-institution, single-arm phase II study. SBRT will be given to a single extracranial metastatic site in combination with nivolumab.
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04042506
Sponsor's protocol ID
J18145
Other IDs
IRB00188445
Status last verified
Apr 2020
First submitted
31 Jul 2019
Last updated
12 Apr 2021
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Nivolumab 10 MG/ML Intravenous Solution [OPDIVO] and Stereotactic Body Radiation Therapy (SBRT) in people with Metastatic Melanoma, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 12 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety of SBRT in the presence of immune checkpoint blockade (ICB) as measured by number of participants experiencing adverse events (time frame: 12 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04042506.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Apr 2021.

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