Neoadjuvant Combination Therapy With Ipilimumab and HighDose IFN-α2b for Melanoma

NCT01608594 | Completed Phase 1 DMC

• 1 other identifier: 11-063
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the safety and potential effectiveness of a new treatment for advanced and recurrent melanoma involving the combination of Ipilimumab and IFN-α2b before surgery and to test for biomarker studies in blood and/or tumor to better understand this disease, how best to treat it and what patients should be treated with this combination.

Conditions

Melanoma

Outcome Measures

Primary Outcomes (1)

• Adverse Events

  To estimate the safety profile of investigational combination biotherapy with standard HDI and ipilimumab at 10 mg/kg and 3 mg/kg

  5 years

Secondary Outcomes (4)

• Pathologic response rate

  1 year

• Radiologic preoperative response rate

  1 year

• Progression Free Survival

  5 years

• Overall Survival

  5 years

Study Arms (2)

Ipilimumab 10 mg/kg + HDI

EXPERIMENTAL

Ipilimumab 10 mg/kg + standard dose IFN alpha

Drug: administration of ipilimumab10mg/kg

Ipilimumab 3mg/kg + HDI

EXPERIMENTAL

Ipilimumab 3mg/kg + standard dose IFN alpha

Drug: administration of ipilimumab 3mg/kg + HDI

Interventions

administration of ipilimumab10mg/kg DRUG

Ipilimumab IV infusion: * Day 0 (within 1-2 weeks of baseline biopsy) every 3 weeks for 2 doses followed by definitive surgery * After surgery recover-y resume at the same dose for 2 additional doses given 3 weeks apart * Dose continued 12 weeks later for 4 additional doses given 12 weeks apart Interferon Alfa-2b will be given concurrently with ipilimumab. Each patient will receive Interferon Alfa-2b at 20 MU/m²/day intravenously for 5 consecutive days out of 7 every week for 4 weeks, followed by 10 MU/m²/d subcutaneously every other day, 3 times each week for 2 weeks, followed by definitive surgery. After surgery recovery, Interferon Alfa-2b will be resumed at 10 MU/m²/d subcutaneously, every other day three times a week for 46 additional weeks.

Also known as: MDX-010, MDX-101, BMS-734016, Yervoy

Ipilimumab 10 mg/kg + HDI

administration of ipilimumab 3mg/kg + HDI DRUG

Ipilimumab IV infusion: * Day 0 (within 1-2 weeks of baseline biopsy) every 3 weeks for 2 doses followed by definitive surgery * After surgery recover-y resume at the same dose for 2 additional doses given 3 weeks apart * Dose continued 12 weeks later for 4 additional doses given 12 weeks apart Interferon Alfa-2b will be given concurrently with ipilimumab. Each patient will receive Interferon Alfa-2b at 20 MU/m²/day intravenously for 5 consecutive days out of 7 every week for 4 weeks, followed by 10 MU/m²/d subcutaneously every other day, 3 times each week for 2 weeks, followed by definitive surgery. After surgery recovery, Interferon Alfa-2b will be resumed at 10 MU/m²/d subcutaneously, every other day three times a week for 46 additional weeks.

Also known as: MDX-010, MDX-101, BMS-734016, Yervoy

Ipilimumab 3mg/kg + HDI

Eligibility Criteria

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

You may qualify if:

• Men and women, at least 18 years of age
• ECOG performance status 0 or 1
• Histologic diagnosis of melanoma staged:
• Tx or T1-4 and
• N1b, or N2b, or N2c, or N3
• M 0 that may present as any of the following groups:
• Primary melanoma with clinically apparent regional lymph node metastases, biopsy confirmed
• Clinically detected recurrence of melanoma at the proximal regional lymph node(s) basin, biopsy confirmed
• Clinically or histologically detected primary melanoma involving multiple regional nodal groups, biopsy confirmed
• Clinically detected single site of nodal metastatic melanoma arising from an unknown primary, biopsy confirmed
• Patients with intransit or satellite metastases with or without lymph node involvement are allowed if considered surgically resectable at baseline by the treating medical oncologist and surgical oncologist.
• NOTE: All patients must be determined to be surgically resectable at baseline to be eligible for this neoadjuvant study.
• Patients must undergo biopsy (punch) or open biopsy (if done as part of a clinically indicated baseline diagnostic procedure) within 14 days of entry into the study. Lymphadenectomy/definitive surgery will be performed after at least 2 and generally not longer than 4 weeks of induction HDI-ipilimumab therapy. Additional delays for definitive lymphadenectomy/surgery are allowed if clinically indicated while awaiting the resolution of potential adverse events from HDI-ipilimumab therapy.
• Patients must have been evaluated by standard-of-care full body imaging studies (CT, PET-CT or MRI) as part of the initial clinical work-up at baseline (no more than 4 weeks prior to study enrollment) and after completion of induction HDI-ipilimumab (at 6-8 weeks after the first dose of ipilimumab/HDI and prior to the definitive lymphadenectomy procedure).
• Required values for initial laboratory tests:

You may not qualify if:

• Clinical, radiological/laboratory, or pathological evidence of distant metastatic disease.
• Evidence of soft tissue involvement by gross extranodal extension of tumor manifest by fixation to the fascia, or matting of nodal tissue that would compromise surgical resection as determined by the surgical oncologist.
• History of acute diverticulitis, intra-abdominal abscess, GI obstruction and abdominal carcinomatosis which are known risk factors for bowel perforation.
• Any other malignancy from which the patient has been disease-free for less than 5 years, with the exception of adequately treated and cured basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix.
• Any underlying medical or psychiatric condition, which in the opinion of the Investigator/Sub-Investigator will make the administration of ipilimumab or HDI hazardous or obscure the interpretation of AEs, such as a condition associated with frequent diarrhea.
• Underlying heart conditions if deemed ineligible for surgery by cardiology consult.
• Any non-oncology vaccine therapy used for prevention of infectious diseases (for up to 1 month before or after any dose of ipilimumab).
• Prior treatment with ipilimumab or CD137 agonist or CTLA-4 inhibitor or agonist.
• Prior radiotherapy, chemotherapy, including infusion or perfusion therapy for current disease or any immunotherapy including tumor vaccines, interferon-alfa, interleukins, levamisole or other biologic response modifiers within the past 4 weeks.
• Concomitant therapy with any of the following: IL 2 or other non-study immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive agents; other investigation therapies; or chronic use of systemic corticosteroids; unless discontinued ≥ 4 weeks. A history of occasional use of steroid inhalers is allowed.
• Women of childbearing potential (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.

Sponsors & Collaborators

• Diwakar Davar: lead

Study Sites (1)

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

Related Publications (2)

• Gorry C, McCullagh L, O'Donnell H, Barrett S, Schmitz S, Barry M, Curtin K, Beausang E, Barry R, Coyne I. Neoadjuvant treatment for stage III and IV cutaneous melanoma. Cochrane Database Syst Rev. 2023 Jan 17;1(1):CD012974. doi: 10.1002/14651858.CD012974.pub2.

  PMID: 36648215 DERIVED

• Tarhini A, Lin Y, Lin H, Rahman Z, Vallabhaneni P, Mendiratta P, Pingpank JF, Holtzman MP, Yusko EC, Rytlewski JA, Rao UNM, Ferris RL, Kirkwood JM. Neoadjuvant ipilimumab (3 mg/kg or 10 mg/kg) and high dose IFN-alpha2b in locally/regionally advanced melanoma: safety, efficacy and impact on T-cell repertoire. J Immunother Cancer. 2018 Oct 23;6(1):112. doi: 10.1186/s40425-018-0428-5.

  PMID: 30352626 DERIVED

MeSH Terms

Conditions

Melanoma

Interventions

Ipilimumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Diwakar Davar, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Medicine - Melanoma/Phase 1 Therapeutics

Study Record Dates

• First Submitted: May 26, 2012
• First Posted: May 31, 2012
• Study Start: May 21, 2013
• Primary Completion: February 14, 2017
• Study Completion: February 27, 2017
• Last Updated: August 28, 2018

Record last verified: 2018-08

Locations

US (1)