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MelanomaPhase 1/2NCT01531244

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

A Phase 1/2 study testing dactinomycin, melphalan and Conditionally replicative adenovirus 3/5-delta in people with Melanoma, run by Washington University School of Medicine.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Melanoma
What is being tested?
dactinomycin, melphalan and Conditionally replicative adenovirus 3/5-delta
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
Dec 2014to Feb 2016
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 13Show fewer
  • 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

Who cannot join

  • 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

About this study

Official title: A Phase I/II Study of Isolated Limb Infusion and Targeted Gene Therapy for Advanced, Unresectable Extremity Melanoma

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.

Conditions
Melanoma
Being tested
dactinomycin, melphalan, Conditionally replicative adenovirus 3/5-delta
Medical subject headings
Melanoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • dactinomycinBiological

    Also called ACT-D, actinomycin C1, actinomycin D, AD, Cosmegen, DACT

    Given via ILI

  • melphalanDrug

    Also called Alkeran, CB-3025, L-PAM, L-phenylalanine mustard, L-Sarcolysin, Melfalan

    Given via ILI

  • Conditionally replicative adenovirus 3/5-deltaBiological

    Also called CRAd 3/5-delta

    Given via ILI

Study groups in NCT01531244
Study groupRoleWhat they receive
Treatment (targeted gene therapy and ILI)ExperimentalPatients receive melphalan and dactinomycin via ILI. Patients then receive CRAd 3/5-delta via ILI.
Receives: Biological: dactinomycin; Drug: melphalan; Biological: Conditionally replicative adenovirus 3/5-delta

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Defined as the dose level at which > 50% of target lesion viral infectivity is achieved and < 2 of 6 patients have dose limiting toxicities.

    Measured: 14 days

  2. Response rate (complete response [CR] + partial response [PR]) of CRAd 3/5-delta in combination with standard M-ILI (Phase II)

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

    Measured: 3 months

  3. Progression Free Survival (Phase II)

    Duration of time from start of treatment to time of progression or death, whichever occurs first.

    Measured: 2 years

Secondary outcomes (2)

  1. Safety of CRAd 3/5-delta in combination with standard M-ILI

    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.

    Measured: 2 years

  2. Infectivity rate of CRAd 3/5-delta

    Lesion biopsies; quantified using immunohistochemical staining method.

    Measured: 2 days; baseline and day 1 or 2 post treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Feb 2012 (estimated)
  2. Study startDec 2014
  3. Primary completionFeb 2016 (estimated)
  4. Study completionFeb 2016 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01531244
Sponsor's protocol ID
11-X335
Status last verified
Jul 2014
First submitted
8 Feb 2012
Last updated
18 Jul 2014
Results posted
No
Data monitoring committee
Yes

Publications

  • Turley RS, Raymond AK, Tyler DS. Regional treatment strategies for in-transit melanoma metastasis. Surg Oncol Clin N Am. 2011 Jan;20(1):79-103. doi: 10.1016/j.soc.2010.09.008.

    PubMed 21111960

  • Aloia TA, Grubbs E, Onaitis M, Mosca PJ, Cheng TY, Seigler H, Tyler DS. Predictors of outcome after hyperthermic isolated limb perfusion: role of tumor response. Arch Surg. 2005 Nov;140(11):1115-20. doi: 10.1001/archsurg.140.11.1115.

    PubMed 16301451

  • Brady MS, Brown K, Patel A, Fisher C, Marx W. A phase II trial of isolated limb infusion with melphalan and dactinomycin for regional melanoma and soft tissue sarcoma of the extremity. Ann Surg Oncol. 2006 Aug;13(8):1123-9. doi: 10.1245/ASO.2006.05.003. Epub 2006 Jun 21.

    PubMed 16791448

  • Beasley GM, Riboh JC, Augustine CK, Zager JS, Hochwald SN, Grobmyer SR, Peterson B, Royal R, Ross MI, Tyler DS. Prospective multicenter phase II trial of systemic ADH-1 in combination with melphalan via isolated limb infusion in patients with advanced extremity melanoma. J Clin Oncol. 2011 Mar 20;29(9):1210-5. doi: 10.1200/JCO.2010.32.1224. Epub 2011 Feb 22.

    PubMed 21343562

  • Kroon HM, Moncrieff M, Kam PC, Thompson JF. Outcomes following isolated limb infusion for melanoma. A 14-year experience. Ann Surg Oncol. 2008 Nov;15(11):3003-13. doi: 10.1245/s10434-008-9954-6. Epub 2008 May 29.

    PubMed 18509706

  • Raymond AK, Beasley GM, Broadwater G, Augustine CK, Padussis JC, Turley R, Peterson B, Seigler H, Pruitt SK, Tyler DS. Current trends in regional therapy for melanoma: lessons learned from 225 regional chemotherapy treatments between 1995 and 2010 at a single institution. J Am Coll Surg. 2011 Aug;213(2):306-16. doi: 10.1016/j.jamcollsurg.2011.03.013. Epub 2011 Apr 13.

    PubMed 21493111

  • Alvarez RD, Barnes MN, Gomez-Navarro J, Wang M, Strong TV, Arafat W, Arani RB, Johnson MR, Roberts BL, Siegal GP, Curiel DT. A cancer gene therapy approach utilizing an anti-erbB-2 single-chain antibody-encoding adenovirus (AD21): a phase I trial. Clin Cancer Res. 2000 Aug;6(8):3081-7.

    PubMed 10955787

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing dactinomycin, melphalan and Conditionally replicative adenovirus 3/5-delta in people with Melanoma, run by Washington University School of Medicine.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 18 Jul 2014. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Optimal tolerated dose (OTD) of CRAd 3/5 (time frame: 14 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01531244, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jul 2014.

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