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

NCT02115243 | Completed Phase 1 DMC

• 1 other identifier: Pro00046479
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

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.

Conditions

Unresectable Melanoma

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability

  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.

  2 years

Secondary Outcomes (2)

• Response Rate

  3 years

• Progression Free Survival

  2 years

Study Arms (1)

Ipi/ILI

OTHER

Patients will receive ipilimumab followed by ILI.

Drug: Ipilimumab

Interventions

Ipilimumab DRUG

Ipi/ILI

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 0-1.
• 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
• Platelet count greater than 75,000/mm3
• Total bilirubin less than 2.0 x ULN
• ALT and AST less than 2.5 x the ULN
• Creatinine less than 2.0 x ULN
• Patient must have a palpable femoral/radial pulse in the affected extremity.

You may not qualify if:

• 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
• 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
• are pregnant or breastfeeding.
• Persons of reproductive potential must agree to use an adequate method of contraception throughout treatment and for at least 26 weeks after ipilimumab is stopped.
• Sexually active WOCBP must use an effective method of birth control during the course of the study, in a manner such that risk of failure is minimized. Before study enrollment, WOCBP must be advised of the importance of avoiding pregnancy during study participation and the potential risk factors for an unintentional pregnancy. All WOCBP MUST have a negative pregnancy test before first receiving ipilimumab. If the pregnancy test is positive, the patient must not receive ipilimumab and must not be enrolled in the study.
• Known brain metastasis.
• Known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C.
• Active clinically serious infection greater than CTCAE Grade 2.

Sponsors & Collaborators

• Duke University: lead

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27707, United States

Location

MeSH Terms

Interventions

Ipilimumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Douglas Tyler, MD

  Duke University

  PRINCIPAL INVESTIGATOR

• April K Salama, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 12, 2014
• First Posted: April 15, 2014
• Study Start: May 1, 2014
• Primary Completion: December 7, 2015
• Study Completion: December 7, 2015
• Last Updated: October 29, 2018

Record last verified: 2018-10

Locations

US (1)