MelanomaPhase 2SARTNCT01565837
Concurrent Ipilimumab and Stereotactic Ablative Radiation Therapy (SART) for Oligometastatic But Unresectable Melanoma
A Phase 2 study testing Ipilimumab and Stereotactic Ablative Radiosurgery (SART) in people with Melanoma, run by Wolfram Samlowski at 1 site in United States.
Trial summary
The purpose of this study is to evaluate if precisely-targeted radiation therapy, known as stereotactic ablative radiotherapy (SART), given during treatment with the drug ipilimumab (Yervoy) will improve survival for patients with melanoma that has spread to five or fewer sites (oligometastatic). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma
- What is being tested?
- Ipilimumab and Stereotactic Ablative Radiosurgery (SART)
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2012to Nov 2017
- 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
- Stage III or IV melanoma (AJCC 6th edition) with 5 or less metastatic sites that are not amenable to curative surgical resection, but can be adequately delineated for SART
- All sites of metastatic disease acceptable except brain-only and eye metastases, provided SART can be safely delivered to the site.
- Up to 2 prior systemic treatments for metastatic disease.
- Mucosal or ocular melanoma is allowed.
- Radiotherapy consultation and insurance preapproval for SART prior to enrollment.
- CT or MRI within 28 days of enrollment showing no evidence of brain metastases. Brain metastases allowed if stable by scans for ≥ 28 days following treatment.
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- CT, PET/CT or MRI scan of chest, abdomen, pelvis (and soft tissue as indicated); bone scan (as indicated); and photographs of skin lesions (if applicable) within 28 days of enrollment.
- Hematology, liver function and renal function lab tests within required parameters.
- Recovered from all prior surgery and/or adjuvant treatment.
- No active or chronic infection with HIV, Hepatitis B or Hepatitis C.
- ECOG Performance Status 0 or 1.
- Men and women ≥ 18 years old.
- Men/Women of childbearing potential must use adequate contraception.
Who cannot join
- Untreated or uncontrolled brain metastases.
- Prior treatment with CTLA-4 agent, PD-1 or PD-1 ligand mAb or inhibitor for metastatic disease or as adjuvant therapy (or participation in blinded study).
- History of melanoma-associated retinopathy.
- History of other active malignancy within last 2 years, except adequately treated basal cell carcinoma or squamous cell skin cancer or carcinoma in situ of cervix, unless disease-free for 2 years.
- Autoimmune disease (vitiligo is not a basis for exclusion).
- History of clinically active diverticulitis (diverticulosis is not exclusion criterion per se).
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- Serious uncontrolled medical disorder or active infection that would impede treatment.
- Underlying medical or psychiatric condition that would cause administration of ipilimumab to be hazardous, or would obscure interpretation of AEs.
- Any non-oncology vaccine therapy up to 1 month before or after any dose of ipilimumab.
- Concomitant therapy with IL-2, interferon, other non-study immunotherapy, or cytotoxic chemotherapy; immune-suppressive agents within 30 days of registration; other investigational therapies; chronic use of systemic corticosteroids (however, a low stable dose steroid for mild brain edema or adrenal insufficiency is allowed; topical and inhaled standard dose corticosteroids are allowed).
- Dementia or significantly altered mental status that would prohibit understanding or rendering of informed consent and compliance with protocol requirements.
- Pregnant or breastfeeding women.
- Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g. infectious) illness.
Trial locations and contacts
1 site in 1 country.
United States1 site, 1 recruiting
- Recruiting
Comprehensive Cancer Centers of Nevada
Las Vegas, Nevada, 89148
Khin Win, 702-419-5550, khin.win@usoncology.com
About this study
Official title: Phase II Evaluation of Concurrent Ipilimumab Therapy and Stereotactic Ablative Radiation Therapy (SART) for Oligometastatic But Unresectable Malignant Melanoma
The purpose of this study is to evaluate if precisely-targeted radiation therapy, known as stereotactic ablative radiotherapy (SART), given during treatment with the drug ipilimumab (Yervoy) will improve survival for patients with melanoma that has spread to five or fewer sites (oligometastatic).
Blood samples will be collected for research purposes. Planned studies include exploration of certain gene mutations and serum markers as predictors of response to ipilimumab treatment. Research lab studies will also evaluate if circulating tumor cells (CTC) can be accurately detected and isolated from the blood using novel laboratory techniques and if they are a prognostic/predictive marker for treatment response. Test results will not be given to participants or their physicians. In some cases, CTC may be grown for long-term cell lines for further research.
Read the detailed description
Primary Objectives:
- To evaluate the effectiveness of concurrent ipilimumab therapy and SART of melanoma based on 1-year and 2-year overall survival.
- To evaluate the safety and tolerability of concurrent ipilimumab therapy and SART of melanoma based on CTCAE grading of toxicities, and to identify any novel or unexpected Grade 3 or 4 toxicities thought specifically related to ipilimumab and concurrent SART during first 3 cycles of ipilimumab therapy (prior to week 9) in a Phase II study.
Secondary Objectives:
- To evaluate the 1-year and 2-year disease control rates (CR+PR+SD)
- Assess treatment response based on Immune Related Response Criteria (irRC) and mWHO criteria.
- Characterize overall survival by Kaplan-Meier analysis.
Exploratory Objectives:
- Evaluate individual lesion control (<25% progression) following body SART at 6, 12, 24 months.
- Describe number of patients requiring retreatment of any local lesion with surgery or other treatments.
- Describe the incidence of new brain metastases following ipilimumab therapy.
- Describe the incidence of treatment related toxicity and/or symptomatic bleeding, perforation, or necrosis at SART treated tumor sites.
- Explore the use of circulating melanoma cells and serum metastasis gene expression levels as prognostic and predictive (intermediate) markers to identify responding patients.
- Assess the effect of therapy on quality of life, using ECOG score as a surrogate.
Study Rationale:
Ipilimumab may markedly enhance the immunologic responses to tumor antigen released from necrotic tumor cells by radiotherapy by promoting cytotoxic T cell activation, while preventing induction of antigen tolerance. In addition, further beneficial immunologic effects may be achieved by the reduction in the amount of viable tumor cell mass. The net effect may be to promote a significantly enhanced antitumor T cell response. This will result in improved 1-year and 2-year survival, especially if a minimal or microscopic disease state can be achieved within a patient following SART.
Biologic Correlation Studies:
There are currently no standard prognostic or predictive markers to evaluate or predict outcome of ipilimumab therapy. This study provides the opportunity for exploratory analysis of several candidate hypotheses that may predict outcome.
- Conditions
- Melanoma
- Being tested
- Ipilimumab, Stereotactic Ablative Radiosurgery (SART)
- Keywords
- Melanoma, Malignant Melanoma, Metastatic, Oligometastatic, Radiosurgery, Radiosurgery, Stereotactic, Stereotactic Radiosurgery, Ipilimumab, Yervoy, MDX-010, Circulating Tumor Cells
- Medical subject headings
- Melanoma, Neoplasm Metastasis, Neoplastic Cells, Circulating
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IpilimumabDrug
Also called Yervoy, MDX-010
Ipilimumab 10mg/kg administered intravenously over 90-minute period every 3 weeks for a total of four doses as tolerated. Maintenance ipilimumab (10 mg/kg intravenously every 3 months) will be administered beginning Week 24, as long as there is clinical benefit in the opinion of the investigator using immune related response criteria, and there are no novel or unexpected Grade 3 or 4 toxicities.
Stereotactic Ablative Radiosurgery (SART)Radiation
Definitive radiotherapy will be administered to up to 1-5 lesions using SART techniques after initial dose of ipilimumab. Radiotherapy will be timed before start of 3rd cycle of ipilimumab treatment to maximize synergy (week 6).
| Study group | Role | What they receive |
|---|---|---|
| Ipilimumab + SART | Experimental | Patients with oligometastatic but unresectable malignant melanoma will receive induction ipilimumab plus concurrent SART followed by maintenance ipilimumab. Receives: Drug: Ipilimumab; Radiation: Stereotactic Ablative Radiosurgery (SART) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability of concurrent ipilimumab and SART - Acute Toxicity
Measured: Week 9
Safety and tolerability of concurrent ipilimumab and SART - Subacute Toxicity
Measured: Week 15
Secondary outcomes (4)
1-year disease control rates (CR+PR+SD) based on irRC and mWHO criteria
Measured: 2 year minimum follow up on study participants
2-year disease control rates (CR+PR+SD) based on irRC and mWHO criteria
Measured: 2 year minimum follow up on study participants
1-year overall survival
Measured: 2 year minimum follow up on study participants
2-year overall survival
Measured: 2 year minimum follow up on study participants
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Mar 2012 (estimated)
- Study startAug 2012
- Primary completionNov 2016 (estimated)
- Study completionNov 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MelanomaStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Wolfram Samlowski
- Sponsor type
- University, hospital or other
- Collaborators
- Comprehensive Cancer Centers of Nevada
- Responsible party
- Sponsor-investigator, Wolfram Samlowski, Comprehensive Cancer Centers of Nevada
- Investigators
- Wolfram Samlowski, MD, Principal investigator, Comprehensive Cancer Centers of Nevada
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01565837
- Sponsor's protocol ID
- BMS CA184-168
- Acronym
- SART
- Status last verified
- Jan 2016
- First submitted
- 26 Mar 2012
- Last updated
- 1 Feb 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 1 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Evaluation of Concurrent Ipilimumab Therapy and Stereotactic Ablative Radiation Therapy (SART) for Oligometastatic But Unresectable Malignant Melanoma
- ClinicalTrials.gov ID
- NCT01565837
- Acronym / sponsor ID
- SART / BMS CA184-168
- Conditions
- Melanoma
- Keywords
- Melanoma, Malignant Melanoma, Metastatic, Oligometastatic, Radiosurgery, Radiosurgery, Stereotactic, Stereotactic Radiosurgery, Ipilimumab
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Wolfram SamlowskiUniversity, hospital or other
- Collaborators
- Comprehensive Cancer Centers of Nevada
- Study start
- Aug 2012
- Primary completion
- Nov 2016 (estimated)
- Study completion
- Nov 2017 (estimated)
- First posted
- 29 Mar 2012 (estimated)
- 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 purpose of this study is to evaluate if precisely-targeted radiation therapy, known as stereotactic ablative radiotherapy (SART), given during treatment with the drug ipilimumab (Yervoy) will improve survival for patients with melanoma that has spread to five or fewer sites (oligometastatic).
Blood samples will be collected for research purposes. Planned studies include exploration of certain gene mutations and serum markers as predictors of response to ipilimumab treatment. Research lab studies will also evaluate if circulating tumor cells (CTC) can be accurately detected and isolated from the blood using novel laboratory techniques and if they are a prognostic/predictive marker for treatment response. Test results will not be given to participants or their physicians. In some cases, CTC may be grown for long-term cell lines for further research.
Detailed description
Primary Objectives:
- To evaluate the effectiveness of concurrent ipilimumab therapy and SART of melanoma based on 1-year and 2-year overall survival.
- To evaluate the safety and tolerability of concurrent ipilimumab therapy and SART of melanoma based on CTCAE grading of toxicities, and to identify any novel or unexpected Grade 3 or 4 toxicities thought specifically related to ipilimumab and concurrent SART during first 3 cycles of ipilimumab therapy (prior to week 9) in a Phase II study.
Secondary Objectives:
- To evaluate the 1-year and 2-year disease control rates (CR+PR+SD)
- Assess treatment response based on Immune Related Response Criteria (irRC) and mWHO criteria.
- Characterize overall survival by Kaplan-Meier analysis.
Exploratory Objectives:
- Evaluate individual lesion control (<25% progression) following body SART at 6, 12, 24 months.
- Describe number of patients requiring retreatment of any local lesion with surgery or other treatments.
- Describe the incidence of new brain metastases following ipilimumab therapy.
- Describe the incidence of treatment related toxicity and/or symptomatic bleeding, perforation, or necrosis at SART treated tumor sites.
- Explore the use of circulating melanoma cells and serum metastasis gene expression levels as prognostic and predictive (intermediate) markers to identify responding patients.
- Assess the effect of therapy on quality of life, using ECOG score as a surrogate.
Study Rationale:
Ipilimumab may markedly enhance the immunologic responses to tumor antigen released from necrotic tumor cells by radiotherapy by promoting cytotoxic T cell activation, while preventing induction of antigen tolerance. In addition, further beneficial immunologic effects may be achieved by the reduction in the amount of viable tumor cell mass. The net effect may be to promote a significantly enhanced antitumor T cell response. This will result in improved 1-year and 2-year survival, especially if a minimal or microscopic disease state can be achieved within a patient following SART.
Biologic Correlation Studies:
There are currently no standard prognostic or predictive markers to evaluate or predict outcome of ipilimumab therapy. This study provides the opportunity for exploratory analysis of several candidate hypotheses that may predict outcome.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ipilimumab + SART | Experimental | Drug: Ipilimumab, Radiation: Stereotactic Ablative Radiosurgery (SART)Patients with oligometastatic but unresectable malignant melanoma will receive induction ipilimumab plus concurrent SART followed by maintenance ipilimumab. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Stage III or IV melanoma (AJCC 6th edition) with 5 or less metastatic sites that are not amenable to curative surgical resection, but can be adequately delineated for SART
- All sites of metastatic disease acceptable except brain-only and eye metastases, provided SART can be safely delivered to the site.
- Up to 2 prior systemic treatments for metastatic disease.
- Mucosal or ocular melanoma is allowed.
- Radiotherapy consultation and insurance preapproval for SART prior to enrollment.
Key exclusion criteria (13 listed)
- Untreated or uncontrolled brain metastases.
- Prior treatment with CTLA-4 agent, PD-1 or PD-1 ligand mAb or inhibitor for metastatic disease or as adjuvant therapy (or participation in blinded study).
- History of melanoma-associated retinopathy.
- History of other active malignancy within last 2 years, except adequately treated basal cell carcinoma or squamous cell skin cancer or carcinoma in situ of cervix, unless disease-free for 2 years.
- Autoimmune disease (vitiligo is not a basis for exclusion).
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 |
|---|---|---|
| IpilimumabAlso: Yervoy, MDX-010Ipilimumab 10mg/kg administered intravenously over 90-minute period every 3 weeks for a total of four doses as tolerated. Maintenance ipilimumab (10 mg/kg intravenously every 3 months) will be administered beginning Week 24, as long as there is clinical benefit in the opinion of the investigator using immune related response criteria, and there are no novel or unexpected Grade 3 or 4 toxicities. | Drug | Ipilimumab + SART |
| Stereotactic Ablative Radiosurgery (SART)Definitive radiotherapy will be administered to up to 1-5 lesions using SART techniques after initial dose of ipilimumab. Radiotherapy will be timed before start of 3rd cycle of ipilimumab treatment to maximize synergy (week 6). | Radiation | Ipilimumab + SART |
Primary outcome
Safety and tolerability of concurrent ipilimumab and SART - Acute Toxicity
Time frame: Week 9
Safety and tolerability of concurrent ipilimumab and SART - Subacute Toxicity
Time frame: Week 15
4 secondary outcomes
1-year disease control rates (CR+PR+SD) based on irRC and mWHO criteria
Time frame: 2 year minimum follow up on study participants
2-year disease control rates (CR+PR+SD) based on irRC and mWHO criteria
Time frame: 2 year minimum follow up on study participants
1-year overall survival
Time frame: 2 year minimum follow up on study participants
2-year overall survival
Time frame: 2 year minimum follow up on study participants
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Feb 2016.
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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.
Wolfram Samlowski, MD principal investigator
Comprehensive Cancer Centers of Nevada
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ipilimumab and Stereotactic Ablative Radiosurgery (SART) in people with Melanoma, run by Wolfram Samlowski 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 13 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: status not confirmed, as of the sponsor's last update on 1 Feb 2016. 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 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Wolfram Samlowski, MD (702-952-1251, wolf.samlowski@usoncology.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and tolerability of concurrent ipilimumab and SART - Acute Toxicity (time frame: Week 9). The study lists 2 primary outcomes in all. 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 1 Feb 2016.