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Isolated Limb Infusion Chemotherapy With Targeted Gene Therapy for Advanced, Unresectable Extremity Melanoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01531244
Recruitment Status : Withdrawn
First Posted : February 10, 2012
Last Update Posted : July 18, 2014
Information provided by (Responsible Party):
Washington University School of Medicine

Brief Summary:
This phase I/II trial studies the safety, best dose and effectiveness of targeted gene therapy combined with isolated limb infusion (ILI) of melphalan and dactinomycin for treating patients with advanced extremity melanoma that cannot be removed by surgery. Adding gene therapy to a standard chemotherapy regimen in the isolated limb may enhance anti-cancer effects by inducing a systemic immune response against the tumor cells.

Condition or disease Intervention/treatment Phase
Melanoma Biological: dactinomycin Drug: melphalan Biological: Conditionally replicative adenovirus 3/5-delta Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II Study of Isolated Limb Infusion and Targeted Gene Therapy for Advanced, Unresectable Extremity Melanoma
Study Start Date : December 2014
Estimated Primary Completion Date : February 2016
Estimated Study Completion Date : February 2016

Arm Intervention/treatment
Experimental: Treatment (targeted gene therapy and ILI)
Patients receive melphalan and dactinomycin via ILI. Patients then receive CRAd 3/5-delta via ILI.
Biological: dactinomycin
Given via ILI
Other Name: ACT-D, actinomycin C1, actinomycin D, AD, Cosmegen, DACT

Drug: melphalan
Given via ILI
Other Name: Alkeran, CB-3025, L-PAM, L-phenylalanine mustard, L-Sarcolysin, Melfalan

Biological: Conditionally replicative adenovirus 3/5-delta
Given via ILI
Other Name: CRAd 3/5-delta

Primary Outcome Measures :
  1. Optimal tolerated dose (OTD) of CRAd 3/5 [ Time Frame: 14 days ]
    Defined as the dose level at which > 50% of target lesion viral infectivity is achieved and < 2 of 6 patients have dose limiting toxicities.

  2. Response rate (complete response [CR] + partial response [PR]) of CRAd 3/5-delta in combination with standard M-ILI (Phase II) [ Time Frame: 3 months ]
    Assessed using revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1)

  3. Progression Free Survival (Phase II) [ Time Frame: 2 years ]
    Duration of time from start of treatment to time of progression or death, whichever occurs first.

Secondary Outcome Measures :
  1. Safety of CRAd 3/5-delta in combination with standard M-ILI [ Time Frame: 2 years ]
    Descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting.

  2. Infectivity rate of CRAd 3/5-delta [ Time Frame: 2 days; baseline and day 1 or 2 post treatment ]
    Lesion biopsies; quantified using immunohistochemical staining method.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patient must have histologically or cytologically confirmed diagnosis of melanoma with advanced, unresectable primary or in transit metastasis
  • Patient must have measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 10 mm with caliper measurement for superficial lesions or computed tomography (CT) scan for deeper lesions; additionally, patients must have no evidence of disease beyond the affected extremity on positron emission tomography (PET)/CT scan
  • Patients may have undergone any previous systemic chemotherapy with a treatment free period of > 4 weeks prior to enrolling on this clinical trial
  • Patient must be > 18 years of age.-Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status =< 2, Karnofsky >= 60%
  • Leukocytes >= 3,000/mcL
  • Absolute neutrophil count >= 1,500/mcL
  • Platelets >= 100,000/mcL
  • Total bilirubin =< 1.5 x institutional upper limit of normal (IULN)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3.0 x IULN
  • Creatinine within normal institutional limits
  • OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
  • Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately
  • Patient (or legally authorized representative if applicable) must be able to understand and willing to sign an institutional review board (IRB) approved written informed consent document

Exclusion Criteria:

  • Patients must not have had previous oncolytic viral therapy
  • Patient must not be receiving any other investigational agents
  • Patient must not have known brain metastases; patients with known brain metastases must be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
  • Patient must not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to melphalan or dactinomycin or other agents used in the study
  • Patient must not have an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Patient must not be pregnant and/or breastfeeding
  • Patient must not be known to be human immunodeficiency virus (HIV)-positive or otherwise immunocompromised (i.e., patient has undergone organ/bone marrow transplant on immunosuppression, patient is or has recently undergone treatment with toxic chemotherapy for another malignancy, etc.) as there is a risk of complications in the use of adenovirus therapy in these patients

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01531244

Sponsors and Collaborators
Washington University School of Medicine
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Principal Investigator: Ryan Fields, M.D. Washington University School of Medicine
Additional Information:

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Responsible Party: Washington University School of Medicine Identifier: NCT01531244    
Other Study ID Numbers: 11-X335
First Posted: February 10, 2012    Key Record Dates
Last Update Posted: July 18, 2014
Last Verified: July 2014
Additional relevant MeSH terms:
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Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
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