A Combination of Ipilimumab and Fotemustine for Treat Unresectable Locally Advanced or Metastatic Melanoma

NCT01654692 | Completed Phase 2 DMC

• 2 other identifiers: NIBIT-M12010-019356-50
• Study Type: interventional
• Target: 86
• Locations: 1 country
• Sites: 7

Brief Summary

This study is designed to assess the safety and efficacy of a combination of ipilimumab and fotemustine in Patients with Unresectable Locally Advanced or Metastatic Malignant Melanoma.

Conditions

Metastatic Malignant Melanoma

Keywords

metastatic melanoma; Ipilimumab

Outcome Measures

Primary Outcomes (1)

• The immune response disease control rate (irDCR) using the immune-related (ir) tumor response criteria of the combination of ipilimumab and fotemustine in patients with unresectable locally advanced or metastatic melanoma.

  Immune-related Disease Control Rate (irDCR) is the proportion of treated subjects with a BOR of confirmed irCR, confirmed irPR or irSD. Tumor assessment (including determination of overall response at each tumor assessment and best overall response (BOR) taken over all tumor assessments prior to subsequent therapy is performed using the immune-related (ir) tumor response criteria.

  Weeks 24

Secondary Outcomes (7)

• safety and feasibility of the combination of ipilimumab and fotemustine

  2 years

• Immune-related Major Durable Disease Control Rate (irMDDCR)

  up to 24 weeks

• Immune-related Objective Response Rate (irORR)

  Weeks 24

• Immune-related Time to Response (irTTR)

  Weeks 24

• Immune-related Progression-Free Survival (irPFS)

  2 years

Study Arms (1)

Single arm of ipilimumab and fotemustine

EXPERIMENTAL

Ipilimumab in combination with Fotemustine

Drug: Ipilimumab and Fotemustine

Interventions

Ipilimumab and Fotemustine DRUG

Ipilimumab: 10 mg/kg q3 weeks for 4 doses, q12 weeks starting at Week 24 Fotemustine: 100 mg/m2 q1 week for 3 doses, q3 weeks starting at Week 9

Also known as: Ipilimumab (Yervoy), Fotemustine (Muphoran)

Single arm of ipilimumab and fotemustine

Eligibility Criteria

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

You may qualify if:

• Histologic diagnosis of malignant melanoma
• Stage III (unresectable) or Stage IV melanoma
• Maximum 1 line of chemotherapy for advanced disease allowed
• No prior chemotherapy within 4 weeks from treatment start (6 weeks in case of nitrosourea)
• No previous systemic corticosteroid therapy within 10 days
• Prior adjuvant treatment with IFN or other immunotherapy allowed
• Asymptomatic brain metastases allowed
• Measurable disease
• Prior treatment of brain metastases. In case stereotactic radiotherapy (or surgery) was not applicable, whole brain radiotherapy should have been performed
• Life expectancy \>= 16 weeks
• ECOG performance status of 0 or 1
• Normal laboratory tests were required
• Negative screening tests for HIV, Hepatitis B, and Hepatitis C.
• Men and women, of and over 18 years old. Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 8 weeks after the study in such a manner that the risk of pregnancy is minimized.

You may not qualify if:

• Any 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, carcinoma in situ of the cervix;
• Primary ocular or mucosal melanoma. Medical History and Concurrent Diseases
• Symptomatic brain metastases requiring immediate local intervention (radiotherapy (RT) and/or surgery)
• Autoimmune disease
• Any underlying medical condition, which in the opinion of the investigator, will make the administration of study drug hazardous or obscure the interpretation of adverse events, such as a condition associated with frequent diarrhea.
• Prohibited Treatments and/or Therapies
• Concomitant therapy with any anti-cancer agent
• Immunosuppressive agents
• Any non-oncology vaccine therapy used for prevention of infectious diseases (for up to 1 month prior to or after any dose of study drug); surgery or radiotherapy ; other investigational anti-cancer therapies; or chronic use of systemic corticosteroids ;
• Previous treatment with other investigational products, including cancer immunotherapy, within 30 days;
• Previous enrollment in another clinical trial or prior treatment with a CD137 agonist or anti-CTLA-4 and/or fotemustine.
• Sex and Reproductive Status
• WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 8 weeks after the study;
• Women who are pregnant or breastfeeding;
• Women with a positive pregnancy test on enrollment or prior to investigational product administration;

Sponsors & Collaborators

• Italian Network for Tumor Biotherapy: lead
• Bristol-Myers Squibb: collaborator

Study Sites (7)

National Institute for Cancer Research

Genoa, Italy

Location

Immunotherapy and Somatic Cell Therapy Unit, Scientific Institute of Romagna

Meldola, Italy

Location

European Institute of Oncology

Milan, Italy

Location

Melanoma Unit, San Raffaele Hospital

Milan, Italy

Location

Surgical Oncology, National Cancer Institute

Milan, Italy

Location

Medical Oncology and Innovative Therapy, National Cancer Institute

Naples, Italy

Location

Medical Oncology and Immunotherapy-University Hospital of Siena

Siena, 53100, Italy

Location

Related Publications (6)

• Robert C, Thomas L, Bondarenko I, O'Day S, Weber J, Garbe C, Lebbe C, Baurain JF, Testori A, Grob JJ, Davidson N, Richards J, Maio M, Hauschild A, Miller WH Jr, Gascon P, Lotem M, Harmankaya K, Ibrahim R, Francis S, Chen TT, Humphrey R, Hoos A, Wolchok JD. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med. 2011 Jun 30;364(26):2517-26. doi: 10.1056/NEJMoa1104621. Epub 2011 Jun 5.

  PMID: 21639810 BACKGROUND

• Hodi FS, O'Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, Gonzalez R, Robert C, Schadendorf D, Hassel JC, Akerley W, van den Eertwegh AJ, Lutzky J, Lorigan P, Vaubel JM, Linette GP, Hogg D, Ottensmeier CH, Lebbe C, Peschel C, Quirt I, Clark JI, Wolchok JD, Weber JS, Tian J, Yellin MJ, Nichol GM, Hoos A, Urba WJ. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010 Aug 19;363(8):711-23. doi: 10.1056/NEJMoa1003466. Epub 2010 Jun 5.

  PMID: 20525992 BACKGROUND

• Avril MF, Aamdal S, Grob JJ, Hauschild A, Mohr P, Bonerandi JJ, Weichenthal M, Neuber K, Bieber T, Gilde K, Guillem Porta V, Fra J, Bonneterre J, Saiag P, Kamanabrou D, Pehamberger H, Sufliarsky J, Gonzalez Larriba JL, Scherrer A, Menu Y. Fotemustine compared with dacarbazine in patients with disseminated malignant melanoma: a phase III study. J Clin Oncol. 2004 Mar 15;22(6):1118-25. doi: 10.1200/JCO.2004.04.165.

  PMID: 15020614 BACKGROUND

• Margolin K, Ernstoff MS, Hamid O, Lawrence D, McDermott D, Puzanov I, Wolchok JD, Clark JI, Sznol M, Logan TF, Richards J, Michener T, Balogh A, Heller KN, Hodi FS. Ipilimumab in patients with melanoma and brain metastases: an open-label, phase 2 trial. Lancet Oncol. 2012 May;13(5):459-65. doi: 10.1016/S1470-2045(12)70090-6. Epub 2012 Mar 27.

  PMID: 22456429 BACKGROUND

• Di Giacomo AM, Ascierto PA, Queirolo P, Pilla L, Ridolfi R, Santinami M, Testori A, Simeone E, Guidoboni M, Maurichi A, Orgiano L, Spadola G, Del Vecchio M, Danielli R, Calabro L, Annesi D, Giannarelli D, Maccalli C, Fonsatti E, Parmiani G, Maio M. Three-year follow-up of advanced melanoma patients who received ipilimumab plus fotemustine in the Italian Network for Tumor Biotherapy (NIBIT)-M1 phase II study. Ann Oncol. 2015 Apr;26(4):798-803. doi: 10.1093/annonc/mdu577. Epub 2014 Dec 23.

  PMID: 25538176 DERIVED

• Di Giacomo AM, Ascierto PA, Pilla L, Santinami M, Ferrucci PF, Giannarelli D, Marasco A, Rivoltini L, Simeone E, Nicoletti SV, Fonsatti E, Annesi D, Queirolo P, Testori A, Ridolfi R, Parmiani G, Maio M. Ipilimumab and fotemustine in patients with advanced melanoma (NIBIT-M1): an open-label, single-arm phase 2 trial. Lancet Oncol. 2012 Sep;13(9):879-86. doi: 10.1016/S1470-2045(12)70324-8. Epub 2012 Aug 13.

  PMID: 22894884 DERIVED

Related Links

• Italian Network for Tumor Biotherapy (NIBIT) web-site, which will allow access to the diverse activities of the Network

MeSH Terms

Conditions

Melanoma

Interventions

Ipilimumab; fotemustine

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

• Michele Maio, MD, PhD

  Medical Oncology and Immunotherapy Unit, University Hospital of Siena

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 18, 2012
• First Posted: August 1, 2012
• Study Start: June 1, 2010
• Primary Completion: May 1, 2012
• Study Completion: September 1, 2014
• Last Updated: May 13, 2015

Record last verified: 2015-05

Locations

IT (7)