A Phase I Trial of Neoadjuvant Ipilimumab Followed by Melphalan Via Isolated Limb Infusion for Patients With Unresectable In-transit Extremity Melanoma

Duke University1 site in 1 country4 target enrollmentMay 2014

ConditionsUnresectable Melanoma

InterventionsIpilimumab

DrugsIpilimumab

Overview

Phase: Phase 1
Intervention: Ipilimumab
Conditions: Unresectable Melanoma
Sponsor: Duke University
Enrollment: 4
Locations: 1
Primary Endpoint: Safety and tolerability
Status: Completed
Last Updated: 7 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The purpose of this study is to determine safety profile, initial response rates and progression free survival for the combination therapy of neoadjuvant system ipilimumab followed by ILI with melphalan in patients with in transit melanoma.

Hypothesis:

The combination of regional LPAm plus systemic ipilimumab will lead to a larger response rate than either therapy alone.

The combination of regional LPAm plus systemic ipilimumab will cause larger changes in immune cell populations than are seen with either therapy along.

Changes in immune cell populations will predict progression free survival.

Registry

clinicaltrials.gov

Start Date

May 2014

End Date

December 7, 2015

Last Updated

7 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Duke University

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Patient must have histologically proven primary or recurrent extremity melanoma, stage IIIB, IIIC, or stage IV (AJCC staging must be documented in patient's medical record, as determined by CT of the chest, abdomen and pelvis, and/or whole body PET scan, and MRI of the brain within 4 weeks prior to administration of study drug)
•Patients with Stage IV disease must have had all distant disease resected at least 30 days prior to regional treatment.
•Patient must be greater than 18 years of age.
•Patient must have an ECOG/Zubrod status of 0-
•Patient's disease must be bi-dimensionally measurable by caliper or radiological method as defined in the RECIST criteria. For subjects with a single lesion, archived tissue must be available for research analysis. The sum of target lesion diameters should be at least 10 mm.
•Disease to be treated by ILI must be distal to the planned site of tourniquet placement (which for the leg is generally the apex of the femoral triangle, or for the arm is distal to the deltoid insertion). If provider feels ILI appropriate with disease in these areas, patient may be enrolled with PI approval.
•Patient must have adequate bone marrow, liver and renal function as assessed by the following:
•Hemoglobin greater than 9.0 g/dl
•White blood count (WBC) of greater than 2000 m3
•Absolute neutrophil count (ANC) greater than 1,000/mm3

Exclusion Criteria

•Cardiac disease: Congestive heart failure greater than class II NYHA. Patients must not have unstable angina (angina symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months
•Autoimmune disease: History of or current active autoimmune diseases, \[e.g. including but not limited to inflammatory bowel diseases \[IBD\], rheumatoid arthritis, autoimmune thyroiditis, autoimmune hepatitis, systemic sclerosis (scleroderma and variants), systemic lupus erythematosus, autoimmune vasculitis, autoimmune neuropathies (such as Guillain-Barre syndrome). Vitiligo and adequately controlled endocrine deficiencies such as hypothyroidism are not exclusionary.\]
•Prior allogeneic stem cell transplantation.
•Patients who have had a history of acute diverticulitis, intra-abdominal abscess, GI obstruction and abdominal carcinomatosis which are known risk factors for bowel perforation.
•History of or current immunodeficiency disease \[e.g. splenectomy or splenic irradiation\].
•Psychiatric conditions or diminished capacity that could compromise the giving of informed consent, or interfere with study compliance; any underlying medical or psychiatric condition, which in the opinion of the investigator will make the administration of ipilimumab hazardous or obscure the interpretation of AEs, such as a condition associated with frequent diarrhea.
•Concomitant therapy with any of the following: IL 2, interferon, or other non-study immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive agents; other investigation therapies; or chronic use of systemic corticosteroids (used in the management of cancer or non-cancer-related illnesses). However, during the course of the study, use of corticosteroids is allowed if used for treating irAEs, adrenal insufficiencies, or if administered at doses of prednisone greater than or equal to 7.5mg daily or equivalent.
•Women of childbearing potential (WOCBP), defined above in Section 5.1, who:
•are unwilling or unable to use an acceptable method of contraception to avoid pregnancy for their entire study period and for at least 26 weeks after cessation of study drug, or
•have a positive pregnancy test at baseline, or

Arms & Interventions

Ipi/ILI

Patients will receive ipilimumab followed by ILI.

Intervention: Ipilimumab

Outcomes

Primary Outcomes

Safety and tolerability

Time Frame: 2 years

The primary objective is to characterize the safety and tolerability of combining IPI and ILI by determining the MTD of IPI when used prior to ILI with LPAM.