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Hepatic Ablation of Melanoma Metastases to Enhance Immunotherapy Response, a Phase I Clinical Trial (HAMMER I)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05169957
Recruitment Status : Recruiting
First Posted : December 27, 2021
Last Update Posted : September 6, 2022
Sponsor:
Information provided by (Responsible Party):
University of Michigan Rogel Cancer Center

Brief Summary:
The primary purpose of this study is to determine the feasibility of liver stereotactic body radiation therapy (SBRT) given in combination with systemic therapy (ipilimumab and nivolumab) in adults with metastatic melanoma with liver metastases who are at significant risk of not benefiting from systemic therapy alone.

Condition or disease Intervention/treatment Phase
Melanoma, Ocular Melanoma, Cutaneous Metastatic Melanoma Melanoma, Mucosal Liver Metastases Drug: Ipilimumab Drug: Nivolumab Procedure: Stereotactic Body Radiation Therapy Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 18 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Hepatic Ablation of Melanoma Metastases to Enhance Immunotherapy Response, a Phase I Clinical Trial (HAMMER I)
Actual Study Start Date : August 9, 2022
Estimated Primary Completion Date : August 2023
Estimated Study Completion Date : August 2024

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Melanoma
MedlinePlus related topics: Melanoma

Arm Intervention/treatment
Experimental: Ipilimumab + Nivolumab + Stereotactic Body Radiation Therapy (SBRT)
Liver SBRT following the second cycle of ipilimumab + nivolumab, which will then be continued up to 4 total cycles prior to subsequent maintenance nivolumab for duration of clinical benefit and tolerance (standard of care systemic therapy)
Drug: Ipilimumab
Ipilimumab administered IV over 85-100 minutes at 3 mg/kg (combined with nivolumab administered IV over 30-60 minutes at 1 mg/kg) every 3 weeks for a total of 4 doses or until progression or unacceptable toxicity.

Drug: Nivolumab
Nivolumab administered IV over 30-60 minutes at 1 mg/kg (combined with ipilimumab administered IV over 85-100 minutes at 3 mg/kg) every 3 weeks for a total of 4 doses of the combination therapy or until progression or unacceptable toxicity. Subjects may receive maintenance dosing of nivolumab alone administered IV over 30-60 minutes at 240 mg every 2 weeks or 480 mg every 4 weeks for a maximum of 52 weeks or until progression or unacceptable toxicity.

Procedure: Stereotactic Body Radiation Therapy
24-45 Gy delivered in three fractions to up to 4 liver metastases
Other Name: SBRT




Primary Outcome Measures :
  1. Percentage of patients who receive all planned radiotherapy. [ Time Frame: Up to 5 weeks after start of study treatment ]
    Percentage of patients who receive all fractions of radiotherapy as planned following the second cycle of ipilimumab/nivolumab (I/N). Radiotherapy will be administered on C2D8 of I/N (±7days)


Secondary Outcome Measures :
  1. Proportion of patients who develop grade 3 or higher toxicity [ Time Frame: Up to 14 weeks after start of study treatment ]
    Proportion of patients who develop grade three or higher toxicities within 60 days after treatment with SBRT or thirty days after the last cycle of I/N, whichever occurs later. Any serious adverse event that occurs after this time frame and is considered related to the study treatment will also be reported.

  2. Overall survival (OS) [ Time Frame: Up to 2 years after end of study treatment ]
    OS defined as the time from start of treatment to death. This will be analyzed using Kaplan-Meier curves and descriptive statistics.

  3. Progression free-survival (PFS) [ Time Frame: Up to 2 years after end of study treatment ]
    PFS defined as the time from start of treatment to date of radiological or clinical progression (leading to withdrawal from the study), or death from any cause, whichever comes first. Assessed Per RECIST v1.1; analyzed using Kaplan-Meier curves and descriptive statistics.

  4. Proportion of patients with local control [ Time Frame: Up to 2 years after end of study treatment ]
    Freedom from local progression (local control) is defined as the lack of progression of the tumors treated by RT, either by tumor size or enhancement. Progression or development of new tumors elsewhere in the liver or outside of the liver would not constitute a local control failure. Tumors which increase in size or demonstrate new or increasing enhancement are considered progression. Analyzed using Kaplan-Meier curves and descriptive statistics.

  5. Objective response rate (ORR) [ Time Frame: Up to 2 years after end of study treatment ]
    The percentage of patients whose disease decreases (Partial response - PR) and/or disappears (Complete response - CR) after treatment according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

  6. Best overall response (BoR) [ Time Frame: Up to 2 years after end of study treatment ]
    The best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started).



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

Inclusion Criteria:

  • Adult patients (≥18 years of age) with histologically or cytologically confirmed metastatic melanoma that is unresectable with liver metastases; disease must be measurable per RECIST criteria
  • Patients must have a life expectancy of at least 6 months
  • Patients must have a performance status of 0 - 2 on the ECOG Performance Scale.
  • Allowable prior therapy:

    • Previous adjuvant or neoadjuvant treatment for melanoma is allowed, which may include molecularly-targeted agents, IFN-alpha, ipilimumab, nivolumab, and pembrolizumab, if it was completed at least 6 weeks before enrollment in the study.
    • Patients who had experienced treatment-related adverse events from prior adjuvant or neoadjuvant treatment for melanoma are allowed if symptoms had returned to baseline or had stabilized.
    • Prior stereotactic radiotherapy (SBRT) of extrahepatic metastases is permitted.
  • Patients must be willing to undergo multiple liver tissue samplings and samples should be of adequate quality for correlative studies
  • Patients must have adequate organ function per protocol
  • Patients must understand and be willing to sign an informed consent form approved for this purpose by the Institutional Review Board (IRB) of the University of Michigan Medical Center indicating that they are aware of the investigational aspects of the treatment and the potential risks.
  • Participants of childbearing potential

    • Female subject of childbearing potential should have a serum pregnancy within 14 days of enrollment and 72 hours prior to receiving the first dose of I/N, and must be willing to use a highly effective method of contraception for the course of the study through 180 days after the last dose of I/N. (Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.)
    • Male subjects of childbearing potential must agree to use an adequate method of contraception, starting with the first dose of study therapy through 180 days after the last dose of study therapy. Sperm donation is prohibited while on study. (Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.)

Exclusion Criteria:

  • Patients will be excluded from the trial if participants have the following:
  • Diffuse involvement of liver by cancer on CT, PET, or MRI imaging
  • More than 4 liver metastases on CT scan at time of initial assessment. If a flare occurs during the initial I/N cycles, up to 8 metastases may be targeted if able to be targeted by a minimum of 8 Gy per fraction while meeting normal tissue constraints.
  • Diagnosis of underlying parenchymal end stage liver disease (cirrhosis) or biliary disease (primary biliary cirrhosis).
  • Other invasive malignancy active within last 3 years, excluding in situ cancers
  • Patients who had received previous systemic anticancer therapy for unresectable or metastatic melanoma
  • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least two weeks prior to enrollment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to enrollment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
  • Has active autoimmune disease that has required systemic treatment within the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs).

    • Note: Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.

  • Require daily corticosteroids >10 mg of prednisone (or its equivalent)

    • Note: Subjects with asthma that require intermittent use of bronchodilators, inhaled steroids, or local steroid injections would NOT be excluded from the study.
    • Note: Patients who require the use of topical steroids would not be excluded.
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with informed consent through 180 days after the last dose of trial treatment.
  • Has a diagnosis of immunodeficiency (including Human Immunodeficiency Virus (HIV) or acquired immunodeficiency (AIDS)-related illness) or has received a bone marrow transplant or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to enrollment.
  • Has a known history of active TB (Bacillus Tuberculosis).
  • Has known active Hepatitis B or Hepatitis C.
  • Prior Gr3/4 life threatening immune related adverse event that is considered an unacceptable risk per the treating investigator
  • Has received a live vaccine within 30 days of enrollment.

    • Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.
    • COVID vaccination acceptable; preferably all doses administered 7 days prior to start of therapy
  • Lacks insurance preapproval for SBRT

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): NCT05169957


Locations
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United States, Michigan
University of Michigan Rogel Cancer Center Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Radiation Oncology    734-936-4300    CancerAnswerLine@med.umich.edu   
Principal Investigator: Michael D. Green, MD, PhD         
Sponsors and Collaborators
University of Michigan Rogel Cancer Center
Investigators
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Principal Investigator: Michael D. Green, MD, PhD University of Michigan Rogel Cancer Center
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Responsible Party: University of Michigan Rogel Cancer Center
ClinicalTrials.gov Identifier: NCT05169957    
Other Study ID Numbers: UMCC 2021.036
HUM00201698 ( Other Identifier: University of Michigan )
First Posted: December 27, 2021    Key Record Dates
Last Update Posted: September 6, 2022
Last Verified: August 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University of Michigan Rogel Cancer Center:
Liver SBRT
ipilimumab
nivolumab
Additional relevant MeSH terms:
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Melanoma
Neoplasm Metastasis
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Neoplastic Processes
Pathologic Processes
Nivolumab
Ipilimumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action