Immunogenicity and Biomarker Analysis of Neoadjuvant Ipilimumab for Melanoma

NCT00972933 | Completed Early Phase 1 DMC

• 1 other identifier: 08-144
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 1

Brief Summary

Ipilimumab is a manufactured monoclonal antibody, much like the antibodies usually made by the human body to fight off infection; however it is not known why the human body does not "fight off" a cancerous tumor. The idea behind developing this experimental drug is to stimulate the immune system to make antibodies to kill cancer cells. This research study is considered "experimental" because it has not received approval from the Food and Drug Administration (FDA) for the treatment of this type of cancer. This monoclonal antibody has been specifically made to block Cytotoxic T Lymphocyte Antigen 4 (CTLA4), which is a protein found on cells of the immune system. CTLA4 seems to slow down the immune response, so blocking it with an anti-CTLA4 antibody may make the immune response more active. The purpose of this study is to see if Ipilimumab affects the response of the patient's immune system toward their cancer.

Conditions

Melanoma

Keywords

Immunogenicity Analysis; Biomarker Analysis; experimental

Outcome Measures

Primary Outcomes (1)

• To study the effects of ipilimumab upon the host immune response in nodal metastatic melanoma and in the peripheral blood comparing pre-treatment with post-treatment (baseline, 6 weeks) immunologic features.

  2.5 years

Secondary Outcomes (4)

• To study the effects of ipilimumab upon the host immune response.

  2.5 years

• To collect pilot data comparing pre-treatment with post-treatment proteomic and genetic features.

  2 years

• To evaluate the clinical efficacy of preoperative neoadjuvant therapy with ipilimumab in high risk clinically and pathologically node-positive melanoma patients (AJCC stage IIIB-C).

  5 years

• To collect safety data and evaluate the safety of neoadjuvant therapy with ipilimumab in high risk clinically and pathologically node-positive melanoma patients (AJCC stage IIIB-C).

  2.5 years

Study Arms (1)

Ipilimumab

EXPERIMENTAL

Induction ipilimumab 10 mg/kg IV day 0, 21 (baseline, week 3) Maintenance Ipilimumab 10 mg/kg IV days 63 (+28 days) and, 84 (+28 days) - (3 weeks apart, starting 2-4 weeks following definitive lymphadenectomy)

Drug: ipilimumab

Interventions

ipilimumab DRUG

Excisional Biopsy - baseline Induction ipilimumab 10 mg/kg IV day 0, 21 - baseline and week 3 Complete lymph node dissection - week ≥ 6 Maintenance Ipilimumab 10 mg/kg IV - Days 63 (+28 days) and, 84 (+28 days) - (3 weeks apart, starting 2-4 weeks following definitive lymphadenectomy)

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

Ipilimumab

Eligibility Criteria

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

You may qualify if:

• Willing and able to give written informed consent.
• Histologic diagnosis of melanoma belonging to T1-4 N1b,2b,2c,3 M 0 AJCC stages, that may present as any of the following groups:
• Primary melanoma with clinically apparent (overt) regional lymph node metastases, confirmed by pathological diagnosis (biopsy).
• Clinically detected recurrence of melanoma at the proximal regional lymph node(s) basin, confirmed by pathological diagnosis (biopsy).
• Clinically or histologically detected primary melanoma involving multiple regional nodal groups, confirmed by pathological diagnosis (biopsy).
• Clinically detected single site of nodal metastatic melanoma arising from an unknown primary, confirmed by pathological diagnosis (biopsy).
• Patients are eligible for this trial either at presentation for primary melanoma with concurrent regional nodal metastasis, or at the time of clinically detected nodal recurrence. 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 will be performed after at least 2 and generally not longer than 4 weeks of ipilimumab therapy. Additional delays for definitive lymphadenectomy are allowed if clinically indicated while awaiting the resolution of potential adverse events from 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 2 doses of ipilimumab (at 6-8 weeks after the first dose of ipilimumab and prior the definitive lymphadenectomy procedure).
• Required values for initial laboratory tests:
• White Blood Cell ≥ 3000/uL
• Absolute Neutrophil Count ≥ 1500/uL
• Platelets ≥ 100 x 103/uL
• Hemoglobin ≥ 10 g/dL
• Creatinine ≤ ULN
• AST/ALT ≤ 2.5 x Upper Limit of Normal (ULN)

You may not qualify if:

• Patients with clinical, radiological/laboratory, or pathological evidence of distant metastatic disease.
• Patients with 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.
• 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.
• 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.
• Autoimmune disease: Patients with a history of inflammatory bowel disease are excluded from this study, as are patients with a history of symptomatic disease (eg, rheumatoid arthritis, systemic progressive sclerosis \[scleroderma\], systemic lupus erythematosus, autoimmune vasculitis \[eg, Wegener's Granulomatosis\]); motor neuropathy considered of autoimmune origin (e.g. Guillain-Barre Syndrome).
• 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.
• Patients with underlying heart conditions who are 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).
• A history of prior treatment with ipilimumab or prior CD137 agonist or CTLA-4 inhibitor or agonist.
• A history of prior radiotherapy, chemotherapy, including infusion or perfusion therapy for his 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, interferon, or other non-study immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive agents; other investigation therapies; or chronic use of systemic corticosteroids; unless discontinued ≥ 4 weeks.
• Women of childbearing potential (WOCBP), defined above in Section 4.1, who:
• are unwilling or unable to use an acceptable method of contraception to avoid pregnancy for their entire study period and for at least 8 weeks after cessation of study drug, or
• have a positive pregnancy test at baseline, or
• are pregnant or breastfeeding.

Sponsors & Collaborators

• Diwakar Davar: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

University of Pittsburgh Medical Center/University of Pittsburgh Cancer Institute

Pittsburgh, Pennsylvania, 15232, United States

Location

Related Publications (3)

• Kobeissi I, Eljilany I, Achkar T, LaFramboise WA, Santana-Santos L, Tarhini AA. A Tumor and Immune-Related Micro-RNA Signature Predicts Relapse-Free Survival of Melanoma Patients Treated with Ipilimumab. Int J Mol Sci. 2023 May 3;24(9):8167. doi: 10.3390/ijms24098167.

  PMID: 37175874 DERIVED

• Retseck J, Nasr A, Lin Y, Lin H, Mendiratta P, Butterfield LH, Tarhini AA. Long term impact of CTLA4 blockade immunotherapy on regulatory and effector immune responses in patients with melanoma. J Transl Med. 2018 Jul 4;16(1):184. doi: 10.1186/s12967-018-1563-y.

  PMID: 29973204 DERIVED

• Tarhini AA, Zahoor H, Lin Y, Malhotra U, Sander C, Butterfield LH, Kirkwood JM. Baseline circulating IL-17 predicts toxicity while TGF-beta1 and IL-10 are prognostic of relapse in ipilimumab neoadjuvant therapy of melanoma. J Immunother Cancer. 2015 Sep 15;3:39. doi: 10.1186/s40425-015-0081-1. eCollection 2015.

  PMID: 26380086 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

  UPMC/UPCI

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: September 3, 2009
• First Posted: September 9, 2009
• Study Start: December 1, 2009
• Primary Completion: July 17, 2013
• Study Completion: September 26, 2017
• Last Updated: December 7, 2017

Record last verified: 2017-12

Locations

US (1)