Melanoma, OcularPhase 1NCT05169957
Hepatic Ablation of Melanoma Metastases to Enhance Immunotherapy Response, a Phase I Clinical Trial (HAMMER I)
A Phase 1 study testing Ipilimumab, Nivolumab and Stereotactic Body Radiation Therapy in people with Melanoma, Ocular and Melanoma, Cutaneous, run by University of Michigan Rogel Cancer Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma, Ocular, Melanoma, Cutaneous, Metastatic Melanoma
- What is being tested?
- Ipilimumab, Nivolumab and Stereotactic Body Radiation Therapy
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- 9 Aug 2022to 17 Jul 2024
- Phase
- Phase 1
- 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
- Adult patients (≥18 years of age) with histologically or cytologically confirmed metastatic melanoma for which surgery is not recommended 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.
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- Prior stereotactic radiotherapy (SBRT) of extrahepatic metastases is permitted.
- Patients must be willing to undergo multiple liver tissue biopsies
- 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.)
Who cannot join
- 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 locally advanced or metastatic invasive malignancy active within last 3 years, excluding in situ or localized cancers or malignancies which have been treated
- Patients who had received previous systemic anticancer therapy for unresectable or metastatic melanoma
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- Has known active 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Michigan Rogel Cancer Center
Ann Arbor, Michigan, 48109
About this study
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.
- Conditions
- Melanoma, Ocular, Melanoma, Cutaneous, Metastatic Melanoma, Melanoma, Mucosal, Liver Metastases
- Being tested
- Ipilimumab, Nivolumab, Stereotactic Body Radiation Therapy
- Keywords
- Liver SBRT, ipilimumab, nivolumab
- Medical subject headings
- Uveal Melanoma, Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IpilimumabDrug
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.
NivolumabDrug
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.
Stereotactic Body Radiation TherapyProcedure or surgery
Also called SBRT
24-45 Gy delivered in three fractions to up to 4 liver metastases
| Study group | Role | What they receive |
|---|---|---|
| Ipilimumab + Nivolumab + Stereotactic Body Radiation Therapy (SBRT) | Experimental | 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) Receives: Drug: Ipilimumab; Drug: Nivolumab; Procedure: Stereotactic Body Radiation Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of patients who receive all planned radiotherapy.
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)
Measured: Up to 5 weeks after start of study treatment
Secondary outcomes (6)
Proportion of patients who develop grade 3 or higher toxicity
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.
Measured: Up to 14 weeks after start of study treatment
Overall survival (OS)
OS defined as the time from start of treatment to death. This will be analyzed using Kaplan-Meier curves and descriptive statistics.
Measured: Up to 2 years after end of study treatment
Progression free-survival (PFS)
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.
Measured: Up to 2 years after end of study treatment
Proportion of patients with local control
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.
Measured: Up to 2 years after end of study treatment
Objective response rate (ORR)
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.
Measured: Up to 2 years after end of study treatment
Best overall response (BoR)
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).
Measured: Up to 2 years after end of study treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Dec 2021
- Study start9 Aug 2022
- Primary completion13 Jun 2023
- Study completion17 Jul 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Melanoma, OcularStudies of the same condition, open and under way.
- More trials run by University of Michigan Rogel Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Michigan Rogel Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Michael D. Green, MD, PhD, Principal investigator, University of Michigan Rogel Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05169957
- Sponsor's protocol ID
- UMCC 2021.036
- Other IDs
- HUM00201698
- Status last verified
- Nov 2024
- First submitted
- 9 Dec 2021
- Last updated
- 5 Nov 2024
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hepatic Ablation of Melanoma Metastases to Enhance Immunotherapy Response, a Phase I Clinical Trial (HAMMER I)
- ClinicalTrials.gov ID
- NCT05169957
- Acronym / sponsor ID
- UMCC 2021.036
- Conditions
- Melanoma, Ocular, Melanoma, Cutaneous, Metastatic Melanoma, Melanoma, Mucosal, Liver Metastases
- Keywords
- Liver SBRT, ipilimumab, nivolumab
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 2 participants (actual)
- Lead sponsor
- University of Michigan Rogel Cancer CenterUniversity, hospital or other
- Study start
- 9 Aug 2022 (actual)
- Primary completion
- 13 Jun 2023 (actual)
- Study completion
- 17 Jul 2024 (actual)
- First posted
- 27 Dec 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ipilimumab + Nivolumab + Stereotactic Body Radiation Therapy (SBRT) | Experimental | Drug: Ipilimumab, Drug: Nivolumab, Procedure: Stereotactic Body Radiation TherapyLiver 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) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Adult patients (≥18 years of age) with histologically or cytologically confirmed metastatic melanoma for which surgery is not recommended 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:
- Patients must be willing to undergo multiple liver tissue biopsies
Key exclusion criteria (22 listed)
- 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 locally advanced or metastatic invasive malignancy active within last 3 years, excluding in situ or localized cancers or malignancies which have been treated
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IpilimumabIpilimumab 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 | Ipilimumab + Nivolumab + Stereotactic Body Radiation Therapy (SBRT) |
| NivolumabNivolumab 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. | Drug | Ipilimumab + Nivolumab + Stereotactic Body Radiation Therapy (SBRT) |
| Stereotactic Body Radiation TherapyAlso: SBRT24-45 Gy delivered in three fractions to up to 4 liver metastases | Procedure or surgery | Ipilimumab + Nivolumab + Stereotactic Body Radiation Therapy (SBRT) |
Primary outcome
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)
6 secondary outcomes
Proportion of patients who develop grade 3 or higher toxicity
Time frame: Up to 14 weeks after start of study treatment
Overall survival (OS)
Time frame: Up to 2 years after end of study treatment
Progression free-survival (PFS)
Time frame: Up to 2 years after end of study treatment
Proportion of patients with local control
Time frame: Up to 2 years after end of study treatment
Objective response rate (ORR)
Time frame: Up to 2 years after end of study treatment
Best overall response (BoR)
Time frame: Up to 2 years after end of study treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Nov 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael D. Green, MD, PhD principal investigator
University of Michigan Rogel Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ipilimumab, Nivolumab and Stereotactic Body Radiation Therapy in people with Melanoma, Ocular and Melanoma, Cutaneous, run by University of Michigan Rogel Cancer Center at 1 site 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 13 inclusion and 22 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: finished, as of the sponsor's last update on 5 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Percentage of patients who receive all planned radiotherapy. (time frame: Up to 5 weeks after start of study treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 5 Nov 2024.