Addition of Ipilimumab (MDX-010) To Isolated Limb Infusion (ILI) With Standard Melphalan and Dactinomycin In The Treatment of Advanced Unresectable Melanoma of The Extremity

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Memorial Sloan-Kettering Cancer Center
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT01323517
First received: March 23, 2011
Last updated: July 7, 2014
Last verified: July 2014
  Purpose

The purpose of this study is to see the effect of adding a systemic study drug, Ipilimumab, to two standard chemotherapy drugs, Melphalan and Dactinomycin. The study drug Ipilimumab is an antibody to a normal protein found in the body, CTLA-4. This protein normally allows the immune system (the body's natural defense system that helps fight infections) uses to quiet an immune response. The study drug works by blocking this protein and allowing the immune system to become more active. This study will investigate the effects, of combining ILI (using two standard drugs to treat melanoma, Melphalan and Dactinomycin), with the study drug, Ipilimumab on advanced Melanoma cancer.


Condition Intervention Phase
Melanoma
Drug: Ipilimumab, Melphalan and Dactinomycin
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of The Addition of Ipilimumab (MDX-010) To Isolated Limb Infusion (ILI) With Standard Melphalan and Dactinomycin In The Treatment of Advanced Unresectable Melanoma of The Extremity

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • To determine progression free survival at one year. [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To determine the safety of additional Ipilimumab. Safety will be evaluated for all treated patients using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • To determine response rates of combination therapy. Tumor assessment will be measured by the immune related response criteria (irRC). [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Progression free survival, from time of ILI, will be determined by measuring the index lesions, non-index lesions, and new lesions as described below. Patients with deep lesions will have repeat CT Scan evaluation to quantitate the lesions.

  • To define the immunologic events and signatures at the tumor site and in the periphery that corresponds to response to Ipilimumab. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Summaries of antibody response, comparison of pretreatment with post-ipilimumab and end of treatment will be assessed for percent of CD4 and CD8 cells as well as CD25, FOXP3, ICOS, CD45, CD67 and CD152 cells among others.


Estimated Enrollment: 39
Study Start Date: February 2011
Estimated Study Completion Date: February 2015
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ipilimumab, Melphalan and Dactinomycin
This is a single-institution phase II trial with a primary outcome of progression free survival (PFS).
Drug: Ipilimumab, Melphalan and Dactinomycin
Isolated limb infusion ((ILI) with Melphalan and Dactinomycin- MSKCC operating room. Ipilimumab- IV administration in outpatient chemotherapy clinic. Induction therapy with Ipilimumab will start 1-3 weeks after ILI in the standard dose of 10mg/kg every 3 weeks for a total of 4 doses. Patients will then receive chronic therapy every 3 months. Patients will be followed every 3 months for 2 years.

  Eligibility

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

Inclusion Criteria:

  • Willing and able to give written informed consent.
  • Histologic diagnosis of melanoma with in transit metastasis Stage IIIB, IIIC, or IV
  • Required values for initial laboratory tests:
  • WBC ≥ 2000/uL
  • ANC ≥ 1000/uL
  • Platelets ≥ 50 x 103/uL
  • Hemoglobin ≥ 8 g/dL
  • Creatinine ≤ 3.0 x ULN
  • AST/ALT ≤ 2.5 x ULN
  • Bilirubin ≤ 3.0 x ULN, (except patients with Gilbert's Syndrome, who must have a total bilirubin less than 3.0 mg/dL)
  • No active or chronic infection with HIV, Hepatitis B, or Hepatitis C.
  • Karnofsky performance status ≥60
  • Men and women, ≥ 18 years of age. Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 8 weeks after the last dose of investigational product, in such a manner that the risk of pregnancy is minimized. WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not post-menopausal. Post-menopause is defined as:
  • Amenorrhea ≥ 12 consecutive months without another cause, or
  • For women with irregular menstrual periods and taking hormone replacement therapy (HRT), a documented serum follicle stimulating hormone (FSH) level ≥ 35 mIU/mL.
  • Women who are using oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy, or are practicing abstinence or where their partner is sterile (eg, vasectomy) should be considered to be of childbearing potential. WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours before the start of ipilimumab.

Exclusion Criteria:

  • Any other malignancy form which the patient has been disease-free for less than 2 years, with the exception of adequately treated and cured basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix.
  • Autoimmune disease: Patients with a history of inflammatory bowel disease are excluded from this study, as are patients with a history of symptomatic disease (eg, rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [eg, Wegener's Granulomatosis]); motor neuropathy considered of autoimmune origin (e.g. Guillain-Barre Syndrome).
  • Any underlying medical or psychiatric condition, which in the opinion of the investigator will make the administration of ipilimumab hazardous or obscure the interpretation of AEs, such as a condition associated with frequent diarrhea.
  • Patients with underlying heart conditions who are deemed ineligible for surgery by cardiology consult
  • Any history of prior treatment with ipilimumab or prior CD137 agonist or CTLA-4 inhibitor or agonist.
  • Concomitant therapy with any of the following: IL-2, interferon, or other non-study immunotherapy regimens; immunosuppressive agents; other investigation therapies; or chronic use of systemic corticosteroids.
  • Women of childbearing potential (WOCBP), who:
  • are unwilling or unable to use an acceptable method of contraception to avoid pregnancy for their entire study period and for at least 8 weeks after cessation of study drug, or
  • have a positive pregnancy test at baseline, or
  • are pregnant or breastfeeding.
  • Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (eg, infectious) illness.
  • Persons of reproductive potential must agree to use an adequate method of contraception throughout treatment and for at least 8 weeks after ipilimumab is stopped.
  • Sexually active WOCBP must use an effective method of birth control during the course of the study, in a manner such that risk of failure is minimized. Before study enrollment, WOCBP must be advised of the importance of avoiding pregnancy during study participation and the potential risk factors for an unintentional pregnancy. All WOCBP MUST have a negative pregnancy test before first receiving ipilimumab. If the pregnancy test is positive, the patient must not receive ipilimumab and must not be enrolled in the study.
  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: NCT01323517

Contacts
Contact: Charlotte Ariyan, MD, PhD 212-639-6280
Contact: Mary Brady, MD, FACS 212-639-8347

Locations
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Charlotte Ariyan, MD, PhD    212-639-6280      
Contact: Mary Brady, MD, FACS    212-639-8347      
Principal Investigator: Charlotte Ariyan, MD, PhD         
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Bristol-Myers Squibb
Investigators
Principal Investigator: Charlotte Ariyan, MD,PhD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT01323517     History of Changes
Other Study ID Numbers: 10-101
Study First Received: March 23, 2011
Last Updated: July 7, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Memorial Sloan-Kettering Cancer Center:
skin
DACTINOMYCIN
MDX-010 (Ipilimumab)
MELPHALAN
Isolated Limb Infusion
10-101

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Melphalan
Dactinomycin
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Myeloablative Agonists
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Protein Synthesis Inhibitors
Enzyme Inhibitors
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on September 22, 2014