A-dmDT390-bisFv(UCHT1) Fusion Protein in Combination With Ionizing Radiation for Treatment of Stage IV Melanoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Angimmune LLC
Sponsor:
Collaborator:
University of Louisville
Information provided by (Responsible Party):
Angimmune LLC
ClinicalTrials.gov Identifier:
NCT01888081
First received: June 21, 2013
Last updated: April 21, 2014
Last verified: April 2014
  Purpose

The purpose of this trial is to study A-dmDT390-bisFv(UCHT1) in combination with ionizing irradiation for the treatment of stage IV melanoma, a disease that is essentially incurable with median overall survival periods that range from 8-16 months.


Condition Intervention Phase
Melanoma
Drug: A-dmDT390-bisFv(UCHT1) (Resimmune™)
Radiation: Ionizing Radiation
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: Phase I/II Trial of A-dmDT390-bisFv(UCHT1) Fusion Protein in Combination With Ionizing Radiation for the Treatment of Stage IV Melanoma

Resource links provided by NLM:


Further study details as provided by Angimmune LLC:

Primary Outcome Measures:
  • Immune-related overall response rate (irORR) [ Time Frame: For up to 1 year post treatment or until disease progression ] [ Designated as safety issue: Yes ]
    Response will be assessed at 2 months, and at least every 3 months (±7 days) thereafter using for up to 1 year after the last treatment administration or until evidence of disease progression. Tumor measurements and therapeutic response will be determined using irRC (Immune Related Response Criteria). At a minimum, CT scans of the chest, abdomen, and pelvis will be performed at study entry, at 2 months, and, if a response or stable disease, at least every 3 months (±7 days) for up to 1 year after the last dose of study drug, and/or at any time there is clinical evidence of disease progression, to evaluate disease status.


Secondary Outcome Measures:
  • Overall survival [ Time Frame: every 3 months for up to 3 years ] [ Designated as safety issue: Yes ]
    Survival should be assessed and a physical exam should be completed every three months as per standard of care


Other Outcome Measures:
  • Treatment Duration [ Time Frame: 4 Days ] [ Designated as safety issue: Yes ]
    Patients will be admitted to the hospital on day 0 for the first two infusions on day 1. Infusions for days 2, 3 and 4 and fractionated radiation will be done in the clinic on an outpatient basis.


Estimated Enrollment: 42
Study Start Date: February 2014
Estimated Primary Completion Date: December 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A-dmDT390-bisFv(UCHT1) with Ionizing Radiation
A-dmDT390-bisFv(UCHT1) Fusion Protein in Combination With Ionizing Radiation
Drug: A-dmDT390-bisFv(UCHT1) (Resimmune™) Radiation: Ionizing Radiation

Detailed Description:

A-dmDT390-bisFv(UCHT1) (Resimmune™), an anti-T cell immunotoxin is currently being studied as a treatment for cutaneous T cell lymphoma and other CD3+ malignant diseases (FDA IND Number: 100712, Scott and White Protocol 071163). During the course of this study, data accumulated that Resimmune could be acting as an immunomodulator. This was based on the observation that four out of six partial responses converted to complete responses at times ranging between 6 and 24 months following the completion of the 4-day treatment protocol and no other treatment took place.

The purpose of this trial is to test the hypothesis that Resimmune can act as an immunomodulator of late stage metastatic melanoma when combined with palliative radiation to induce the priming of activated T cells with tumor antigens. The primary objective of this study is to determine the safety of combining Resimmune with palliative radiation therapy in patients with stage IV melanoma. A secondary objective is to document the tumor response and duration of response at irradiated and unirradiated sites (the abscopal effect). An additional secondary objective is to determine if T cell activation occurs following administration of A-dmDT390-bisFv(UCHT1) and local radiation to a metastatic lesion of melanoma.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • All patients must have histologically proven stage IV metastatic melanoma consisting of at least two lesions
  • Patients must have a performance status of < 2 on Eastern Cooperative Oncology Group scale (see Appendix).
  • Patients must have bilirubin < 1.5 mg/dL, transaminases < 2.5 X ULN, albumin > 3 gm/dL, creatinine < 2.0 mg/dL, adequate pulmonary function by physical exam and pulse oximetry and adequate cardiac reserve (EF > 50% normal). Patients must have a normal echocardiogram without any evidence of cardiac chamber hypertrophy, dilatation or hypokinesis.
  • Patients must give written informed consent prior to registration.
  • Females and males must be willing to use an approved form of birth control while on this study and for 2 weeks after completion.
  • Patients of ages 18-80 are eligible provided they have stage IV melanoma and are negative for BRAF or have failed BRAF inhibitor treatment or if they have failed or are intolerant to other established therapy known to provide clinical benefit for their condition or if they have been adequately consented and agreed to forgo FDA approved clinically meaningful therapy

Exclusion Criteria:

  • Inability to give informed consent because of psychiatric problems, or complicated medical problems.
  • Serious concurrent medical problems, uncontrolled infections, or disseminated intravascular coagulopathy (DIC).
  • Preexisting cardiovascular disease, the only exception being well controlled essential hypertension with a sitting blood pressure of <155 systolic and <90 diastolic without any evidence of structural heart disease or one episode of myocardial infarction > 8 months ago. A past history of the any of the following are exclusions: congestive heart failure, atrial fibrillation, pulmonary hypertension, anticoagulant drug therapy, thromboembolic events, cardiomyopathy or a myocardial infarction within the past 8 months.
  • Pregnant or nursing women will be excluded from study.
  • History of congestive heart failure.
  • History of cirrhosis of the liver
  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: NCT01888081

Contacts
Contact: Brown Cancer Center Clinical Trials Office 502-562-3429 ctobcc@louisville.edu

Locations
United States, Kentucky
James Graham Brown Cancer Center Recruiting
Louisville, Kentucky, United States, 40202
Contact: Sarah Bernstein, RN, BSN    502-540-1537    sarah.bernstein@louisville.edu   
Principal Investigator: Jason A Chesney, MD, PhD         
Sponsors and Collaborators
Angimmune LLC
University of Louisville
Investigators
Principal Investigator: Jason Chesney, MD, PhD James Graham Brown Cancer Center, University of Louisville
  More Information

No publications provided

Responsible Party: Angimmune LLC
ClinicalTrials.gov Identifier: NCT01888081     History of Changes
Other Study ID Numbers: BCC-MEL-13
Study First Received: June 21, 2013
Last Updated: April 21, 2014
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on July 24, 2014