- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01565837
Concurrent Ipilimumab and Stereotactic Ablative Radiation Therapy (SART) for Oligometastatic But Unresectable Melanoma (SART)
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.
Study Overview
Status
Conditions
Intervention / Treatment
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 Type
Enrollment (Anticipated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Wolfram Samlowski, MD
- Phone Number: 702-952-1251
- Email: wolf.samlowski@usoncology.com
Study Contact Backup
- Name: Khin Win
- Phone Number: 702-419-5550
- Email: khin.win@usoncology.com
Study Locations
-
-
Nevada
-
Las Vegas, Nevada, United States, 89148
- Recruiting
- Comprehensive Cancer Centers of Nevada
-
Contact:
- Khin Win
- Phone Number: 702-419-5550
- Email: khin.win@usoncology.com
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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.
- 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.
Exclusion Criteria:
- 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).
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Ipilimumab + SART
Patients with oligometastatic but unresectable malignant melanoma will receive induction ipilimumab plus concurrent SART followed by maintenance ipilimumab.
|
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.
Other Names:
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).
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Safety and tolerability of concurrent ipilimumab and SART - Acute Toxicity
Time Frame: Week 9
|
Week 9
|
Safety and tolerability of concurrent ipilimumab and SART - Subacute Toxicity
Time Frame: Week 15
|
Week 15
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
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 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
|
2 year minimum follow up on study participants
|
1-year overall survival
Time Frame: 2 year minimum follow up on study participants
|
2 year minimum follow up on study participants
|
2-year overall survival
Time Frame: 2 year minimum follow up on study participants
|
2 year minimum follow up on study participants
|
Collaborators and Investigators
Sponsor
Collaborators
Study record dates
Study Major Dates
Study Start
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- Neuroendocrine Tumors
- Nevi and Melanomas
- Melanoma
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Immune Checkpoint Inhibitors
- Ipilimumab
Other Study ID Numbers
- BMS CA184-168
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Melanoma
-
H. Lee Moffitt Cancer Center and Research InstituteTurnstone Biologics, Corp.RecruitingMetastatic Melanoma | Conjunctival Melanoma | Ocular Melanoma | Unresectable Melanoma | Uveal Melanoma | Cutaneous Melanoma | Mucosal Melanoma | Iris Melanoma | Acral Melanoma | Non-Cutaneous MelanomaUnited States
-
University of Southern CaliforniaNational Cancer Institute (NCI)CompletedRecurrent Melanoma | Stage IV Melanoma | Mucosal Melanoma | Ciliary Body and Choroid Melanoma, Medium/Large Size | Ciliary Body and Choroid Melanoma, Small Size | Iris Melanoma | Metastatic Intraocular Melanoma | Recurrent Intraocular Melanoma | Stage IV Intraocular Melanoma | Stage IIIA Melanoma | Stage... and other conditionsUnited States
-
National Cancer Institute (NCI)CompletedRecurrent Melanoma | Stage IIIA Melanoma | Stage IIIB Melanoma | Stage IIIC Melanoma | Stage IIB Melanoma | Stage IIC Melanoma | Stage IA Melanoma | Stage IB Melanoma | Stage IIA MelanomaUnited States
-
MelanomaPRO, RussiaRecruitingMelanoma | Melanoma (Skin) | Melanoma Stage IV | Melanoma Stage III | Melanoma, Stage II | Melanoma, Uveal | Melanoma in Situ | Melanoma, OcularRussian Federation
-
National Cancer Institute (NCI)CompletedStage IV Melanoma | Ciliary Body and Choroid Melanoma, Medium/Large Size | Iris Melanoma | Stage IIIA Melanoma | Stage IIIB Melanoma | Stage IIIC Melanoma | Extraocular Extension Melanoma | Stage IIB Melanoma | Stage IIC MelanomaUnited States
-
Rutgers, The State University of New JerseyNational Cancer Institute (NCI); University of VirginiaCompletedStage IIIB Skin Melanoma | Stage IIIC Skin Melanoma | Stage III Skin Melanoma | Stage IIA Skin Melanoma | Stage IIB Skin Melanoma | Stage IIC Skin Melanoma | Stage IIIA Skin Melanoma | Stage IA Skin Melanoma | Stage IB Skin Melanoma | Stage 0 Skin Melanoma | Stage I Skin Melanoma | Stage II Skin MelanomaUnited States
-
Roswell Park Cancer InstituteNational Cancer Institute (NCI); National Comprehensive Cancer NetworkTerminatedRecurrent Melanoma | Stage IV Melanoma | Metastatic Intraocular Melanoma | Recurrent Intraocular Melanoma | Stage IV Intraocular Melanoma | Stage IIIA Melanoma | Stage IIIB Melanoma | Stage IIIC Melanoma | Extraocular Extension Melanoma | Stage IIIA Intraocular Melanoma | Stage IIIB Intraocular Melanoma | Stage...United States
-
Mayo ClinicNational Cancer Institute (NCI)CompletedRecurrent Melanoma | Stage IV Melanoma | Stage IIIA Melanoma | Stage IIIB Melanoma | Stage IIIC Melanoma | Stage IIB Melanoma | Stage IIC Melanoma | Stage IIA MelanomaUnited States
-
Emory UniversityGenentech, Inc.Active, not recruitingStage IV Skin Melanoma | Stage IIIB Skin Melanoma | Stage IIIC Skin Melanoma | Unresectable Melanoma | Stage III Melanoma | Stage IIIA Skin Melanoma | Cutaneous Melanoma, Stage III | Cutaneous Melanoma, Stage IVUnited States
-
BiocadRecruitingMelanoma | Melanoma (Skin) | Melanoma Stage IV | Melanoma Stage III | Melanoma Metastatic | Melanoma Unresectable | Melanoma AdvancedIndia, Russian Federation, Belarus
Clinical Trials on Ipilimumab
-
Shanghai Henlius BiotechRecruitingHealthy Male VolunteersChina
-
Bristol-Myers SquibbCompletedLung CancerItaly, United States, France, Russian Federation, Spain, Argentina, Belgium, Brazil, Canada, Chile, Czechia, Germany, Greece, Hungary, Mexico, Netherlands, Poland, Romania, Switzerland, Turkey, United Kingdom
-
Takara Bio Inc.TheradexCompletedMalignant MelanomaUnited States
-
Italian Network for Tumor Biotherapy FoundationBristol-Myers SquibbUnknown
-
National Health Research Institutes, TaiwanNational Taiwan University Hospital; Mackay Memorial Hospital; China Medical... and other collaboratorsRecruitingHepatocellular Carcinoma (HCC)Taiwan
-
MacroGenicsCompletedMelanoma | Non Small Cell Lung CancerUnited States
-
Gustave Roussy, Cancer Campus, Grand ParisCompleted
-
National Cancer Institute (NCI)RecruitingGlioblastoma | Malignant Glioma | GliosarcomaUnited States
-
Ontario Clinical Oncology Group (OCOG)Bristol-Myers SquibbActive, not recruitingMetastatic Renal Cell CarcinomaCanada, Australia
-
Bristol-Myers SquibbCompletedCarcinoma, Renal CellUnited States, Italy, Brazil, Argentina, Australia, Austria, Belgium, Canada, Chile, China, Colombia, Czechia, France, Germany, Japan, Mexico, Netherlands, Poland, Romania, Russian Federation, Singapore, Spain, Switzerland, Turkey, United...