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

This study is not yet open for participant recruitment.
Verified February 2014 by Washington University School of Medicine
Sponsor:
Information provided by (Responsible Party):
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT01531244
First received: February 8, 2012
Last updated: February 13, 2014
Last verified: February 2014
  Purpose

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 Intervention Phase
Melanoma
Biological: dactinomycin
Drug: melphalan
Biological: Conditionally replicative adenovirus 3/5-delta
Phase 1
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: A Phase I/II Study of Isolated Limb Infusion and Targeted Gene Therapy for Advanced, Unresectable Extremity Melanoma

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

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

  • 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 ] [ Designated as safety issue: No ]
    Assessed using revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1)

  • Progression Free Survival (Phase II) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Duration of time from start of treatment to time of progression or death, whichever occurs first.


Secondary Outcome Measures:
  • Safety of CRAd 3/5-delta in combination with standard M-ILI [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    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.

  • Infectivity rate of CRAd 3/5-delta [ Time Frame: 2 days; baseline and day 1 or 2 post treatment ] [ Designated as safety issue: No ]
    Lesion biopsies; quantified using immunohistochemical staining method.


Estimated Enrollment: 49
Study Start Date: December 2014
Estimated Study Completion Date: February 2016
Estimated Primary Completion Date: February 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

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

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01531244

Contacts
Contact: Ryan Fields, M.D. 314-747-2938 fieldsr@wudosis.wustl.edu

Locations
United States, Missouri
Washington University School of Medicine Not yet recruiting
St. Louis, Missouri, United States, 63110
Contact: Ryan Fields, M.D.    314-747-2938    fieldsr@wudosis.wustl.edu   
Sub-Investigator: Jonathan Mitchem, M.D.         
Sub-Investigator: David Curiel, M.D., Ph.D.         
Sub-Investigator: Gerald Linette, M.D.         
Sub-Investigator: Lynn Cornelius, M.D.         
Sub-Investigator: Jeffrey Moley, M.D.         
Sub-Investigator: Patrick Geraghty, M.D.         
Sponsors and Collaborators
Washington University School of Medicine
Investigators
Principal Investigator: Ryan Fields, M.D. Washington University School of Medicine
  More Information

Additional Information:
Publications:

Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT01531244     History of Changes
Other Study ID Numbers: 11-X335
Study First Received: February 8, 2012
Last Updated: February 13, 2014
Health Authority: United States: Institutional Review Board

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
Dactinomycin
Melphalan
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Anti-Bacterial Agents
Anti-Infective Agents
Myeloablative Agonists
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Alkylating
Alkylating Agents

ClinicalTrials.gov processed this record on April 17, 2014