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

Sponsor
Washington University School of Medicine (Other)
Overall Status
Withdrawn
CT.gov ID
NCT01531244
Collaborator
(none)
0
Enrollment
1
Arm
14
Duration (Months)

Study Details

Study Description

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
  • Biological: dactinomycin
  • Drug: melphalan
  • Biological: Conditionally replicative adenovirus 3/5-delta
 Phase 1/Phase 2

Study Design

Study Type:
Interventional
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 :
Dec 1, 2014
Anticipated Primary Completion Date :
Feb 1, 2016
Anticipated Study Completion Date :
Feb 1, 2016

Arms and Interventions

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 Names:
  • ACT-D, actinomycin C1, actinomycin D, AD, Cosmegen, DACT

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

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

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Optimal tolerated dose (OTD) of CRAd 3/5 [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) [3 months]

      Assessed using revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1)

    3. Progression Free Survival (Phase II) [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 [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 [2 days; baseline and day 1 or 2 post treatment]

      Lesion biopsies; quantified using immunohistochemical staining method.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    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

    Contacts and Locations

    Locations

    No locations specified.

    Sponsors and Collaborators

    • Washington University School of Medicine

    Investigators

    • Principal Investigator: Ryan Fields, M.D., Washington University School of Medicine

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    Responsible Party:
    Washington University School of Medicine
    ClinicalTrials.gov Identifier:
    NCT01531244
    Other Study ID Numbers:
    • 11-X335
    First Posted:
    Feb 10, 2012
    Last Update Posted:
    Jul 18, 2014
    Last Verified:
    Jul 1, 2014
    Additional relevant MeSH terms:
    Melanoma
    Dactinomycin
    Cactinomycin
    Melphalan

    Study Results

    No Results Posted as of Jul 18, 2014