Concurrent Ipilimumab and Stereotactic Ablative Radiation Therapy (SART) for Oligometastatic But Unresectable Melanoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by Comprehensive Cancer Centers of Nevada
Sponsor:
Collaborator:
Comprehensive Cancer Centers of Nevada
Information provided by (Responsible Party):
Wolfram Samlowski, Comprehensive Cancer Centers of Nevada
ClinicalTrials.gov Identifier:
NCT01565837
First received: March 26, 2012
Last updated: February 5, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Melanoma
Drug: Ipilimumab
Radiation: Stereotactic Ablative Radiosurgery (SART)
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Evaluation of Concurrent Ipilimumab Therapy and Stereotactic Ablative Radiation Therapy (SART) for Oligometastatic But Unresectable Malignant Melanoma

Resource links provided by NLM:


Further study details as provided by Comprehensive Cancer Centers of Nevada:

Primary Outcome Measures:
  • Safety and tolerability of concurrent ipilimumab and SART - Acute Toxicity [ Time Frame: Week 9 ] [ Designated as safety issue: Yes ]
  • Safety and tolerability of concurrent ipilimumab and SART - Subacute Toxicity [ Time Frame: Week 15 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 1-year disease control rates (CR+PR+SD) based on irRC and mWHO criteria [ Time Frame: 2 year minimum follow up on study participants ] [ Designated as safety issue: No ]
  • 2-year disease control rates (CR+PR+SD) based on irRC and mWHO criteria [ Time Frame: 2 year minimum follow up on study participants ] [ Designated as safety issue: No ]
  • 1-year overall survival [ Time Frame: 2 year minimum follow up on study participants ] [ Designated as safety issue: No ]
  • 2-year overall survival [ Time Frame: 2 year minimum follow up on study participants ] [ Designated as safety issue: No ]

Estimated Enrollment: 50
Study Start Date: August 2012
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ipilimumab + SART
Patients with oligometastatic but unresectable malignant melanoma will receive induction ipilimumab plus concurrent SART followed by maintenance ipilimumab.
Drug: 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:
  • Yervoy
  • MDX-010
Radiation: 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).

Detailed Description:

Primary Objectives:

  1. To evaluate the effectiveness of concurrent ipilimumab therapy and SART of melanoma based on 1-year and 2-year overall survival.
  2. 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:

  1. To evaluate the 1-year and 2-year disease control rates (CR+PR+SD)
  2. Assess treatment response based on Immune Related Response Criteria (irRC) and mWHO criteria.
  3. Characterize overall survival by Kaplan-Meier analysis.

Exploratory Objectives:

  1. Evaluate individual lesion control (<25% progression) following body SART at 6, 12, 24 months.
  2. Describe number of patients requiring retreatment of any local lesion with surgery or other treatments.
  3. Describe the incidence of new brain metastases following ipilimumab therapy.
  4. Describe the incidence of treatment related toxicity and/or symptomatic bleeding, perforation, or necrosis at SART treated tumor sites.
  5. Explore the use of circulating melanoma cells and serum metastasis gene expression levels as prognostic and predictive (intermediate) markers to identify responding patients.
  6. 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01565837

Contacts
Contact: Wolfram Samlowski, MD 702-952-1251 wolf.samlowski@usoncology.com
Contact: Joyson Pekkattil 702-952-3714 joyson.pekkattil@usoncology.com

Locations
United States, Nevada
Comprehensive Cancer Centers of Nevada Recruiting
Las Vegas, Nevada, United States, 89148
Contact: Joyson Pekkattil    702-952-3714    joyson.pekkattil@usoncology.com   
Sponsors and Collaborators
Wolfram Samlowski
Comprehensive Cancer Centers of Nevada
Investigators
Principal Investigator: Wolfram Samlowski, MD Comprehensive Cancer Centers of Nevada
  More Information

No publications provided

Responsible Party: Wolfram Samlowski, Physician, Comprehensive Cancer Centers of Nevada; Member, Developmental Therapeutics and Genitourinary Committee, US Oncology Research; Clinical Professor, University of Nevada, Reno, Comprehensive Cancer Centers of Nevada
ClinicalTrials.gov Identifier: NCT01565837     History of Changes
Other Study ID Numbers: BMS CA184-168
Study First Received: March 26, 2012
Last Updated: February 5, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Comprehensive Cancer Centers of Nevada:
Melanoma
Malignant Melanoma
Metastatic
Oligometastatic
Radiosurgery
Radiosurgery, Stereotactic
Stereotactic Radiosurgery
Ipilimumab
Yervoy
MDX-010
Circulating Tumor Cells

Additional relevant MeSH terms:
Melanoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Neuroectodermal Tumors
Neuroendocrine Tumors
Nevi and Melanomas
Antibodies, Monoclonal
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 29, 2014