A Study of Fotemustine(FTM) Vs FTM and Ipilimumab (IPI) or IPI and Nivolumab in Melanoma Brain Metastasis

NCT02460068 | Unknown Phase 3 DMC

• 1 other identifier: NIBIT-M2
• Study Type: interventional
• Target: 168
• Locations: 1 country
• Sites: 11

Brief Summary

This Phase 3, open-label, triple arm study aims to evaluate the overall survival (OS) of fotemustine versus the combination of ipilimumab and fotemustine or the combination of Ipilimumab and nivolumab in patients with metastatic melanoma with brain metastasis.

Conditions

Brain Metastases

Keywords

melanoma brain metastases; nivolumab; ipilimumab

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS)

  To compare the efficacy of the combination of ipilimumab and fotemustine or the Combination of ipilimumab and nivolumab versus fotemustine in terms of overall survival (OS) in patients with metastatic melanoma with brain metastasis.Overall Survival (OS) is defined as the time from randomization until the date of death. For those subjects who have not died, OS will be censored at the recorded last date of subject contact, and for subjects with a missing recorded last date of contact, OS will be censored at the last date the subject was known to be alive.

  2 years

Secondary Outcomes (11)

• safety (adverse events)

  2 years

• m-WHO and immune-related Disease Control Rate (DCR) in and outside the brain

  Weeks 24

• Immune-related Progression-free Survival (irPFS)

  2 years

• m-WHO Progression-free Survival (irPFS)

  2 years

• Objective Response Rate (ORR)

  Weeks 24

Study Arms (3)

fotemustine

ACTIVE COMPARATOR

fotemustine alone

Drug: Fotemustine

fotemustine and ipilimumab

EXPERIMENTAL

fotemustine in combination with ipilimumab

Drug: Fotemustine and Ipilimumab

ipilimumab and nivolumab

EXPERIMENTAL

ipilimumab in combination with nivolumab

Drug: Ipilimumab and nivolumab

Interventions

Fotemustine DRUG

Fotemustine: fotemustine at 100 mg/mq intravenously (i.v.) over 60 minutes once every week for 3 doses, and once every 3 weeks from week 9 for 6 doses.

Also known as: Fotemustine (Muphoran);

fotemustine

Fotemustine and Ipilimumab DRUG

Fotemustine and ipilimumab:fotemustine 100 mg/m2 i.v. over 60 minutes once every week for 3 weeks (Weeks 1, 2, 3) plus ipilimumab at 10 mg/kg i.v. over 90 minutes every 3 weeks for 4 cycles (Weeks 1, 4, 7, 10); fotemustine 100 mg/m2 i.v. over 60 minutes once every 3 weeks from week 9 for 6 doses plus ipilimumab at 10 mg/kg i.v. over 90 minutes every 12 weeks from week 24.

Also known as: Fotemustine (Muphoran);, Ipilimumab (YERVOY)

fotemustine and ipilimumab

Ipilimumab and nivolumab DRUG

ipilimumab and nivolumab: ipilimumab 3 mg/kg i.v over 90 minutes combined with nivolumab 1 mg/kg i.v over 60 minutes every three weeks for 4 doses, then nivolumab 3 mg/kg IV over 60 minutes every two weeks.

Also known as: Ipilimumab (YERVOY), Nivolumab (OPDIVO)

ipilimumab and nivolumab

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 malignant melanoma;
• Stage IV melanoma;
• No prior therapy for advanced (unresectable Stage III or Stage IV) disease;
• No previous systemic corticosteroid therapy within 7 days;
• Prior adjuvant treatment with IFN or other immunotherapy allowed with exception of anti-CTLA-4;
• Presence of asymptomatic brain metastases: patients must have measurable metastases in the brain, defined as lesions that can be accurately measured in 2 dimensions as ≥ 0.5 cm (maximum 2 cm) in the brain MRI with contrast;
• Pts who have been previously treated with brain stereotactic radiotherapy (SRT), whole-brain radiotherapy (WBRT) and/or surgery, must have developed new measurable brain lesions;
• Life expectancy ≥ 12 weeks;
• ECOG performance status of 0 or 1 (see Appendix 2);
• Normal laboratory tests were required.
• Subjects must have known BRAF V600E mutation status or consent to BRAF V600E mutation testing per local institutional standard.
• 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 use appropriate method(s) of contraception. WOCBP should use an adequate method to avoid pregnancy for 23 weeks (30 days plus the time required for nivolumab to undergo five half-lives) after the last dose of investigational drug

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;
• Prior treatment with anti-CTLA-4 and/or , anti-PD1/PD-L1 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;
• Sexually active fertile men not using effective birth control if their partners are WOCBP.

Sponsors & Collaborators

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

Study Sites (11)

Medical Oncology, Cancer Institute "Giovanni Paolo II"

Bari, 70124, Italy

NOT YET RECRUITING

Medical Oncology, Pope Giovanni XXIII Hospital

Bergamo, 24127, Italy

RECRUITING

National Institute for Cancer Research

Genoa, 16132, Italy

NOT YET RECRUITING

Immunotherapy and Somatic Cell Therapy Unit, Scientific Institute of Romagna

Meldola, 47014, Italy

RECRUITING

Surgical Oncology, National Cancer Institute

Milan, 20133, Italy

RECRUITING

European Institute of Oncology

Milan, 20141, Italy

ACTIVE NOT RECRUITING

Medical Oncology and Innovative Therapy, National Cancer Institute

Naples, 80131, Italy

ACTIVE NOT RECRUITING

esophageal and melanoma oncology, Istituto Oncologico Veneto

Padua, 35128, Italy

NOT YET RECRUITING

Medical Oncology, National Cancer Institute "Regina Elena"

Rome, 0014, Italy

ACTIVE NOT RECRUITING

Medical Oncology and Immunotherapy Unit, University Hospital of Siena

Siena, 53100, Italy

RECRUITING

S C Dermatology, A.O.U. City of Health and Science of Turin

Turin, 10126, Italy

NOT YET RECRUITING

Related Publications (5)

• 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, 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 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 BACKGROUND

• Wolchok JD, Kluger H, Callahan MK, Postow MA, Rizvi NA, Lesokhin AM, Segal NH, Ariyan CE, Gordon RA, Reed K, Burke MM, Caldwell A, Kronenberg SA, Agunwamba BU, Zhang X, Lowy I, Inzunza HD, Feely W, Horak CE, Hong Q, Korman AJ, Wigginton JM, Gupta A, Sznol M. Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med. 2013 Jul 11;369(2):122-33. doi: 10.1056/NEJMoa1302369. Epub 2013 Jun 2.

  PMID: 23724867 BACKGROUND

Related Links

• Fondazione NIBIT

MeSH Terms

Conditions

Brain Neoplasms

Interventions

fotemustine; Ipilimumab; Nivolumab

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System 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

• Anna Maria Di Giacomo, PhD,MD

  Medical Oncology and Immunotherapy Unit, University Hospital of Siena

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Anna Maria Di Giacomo, PhD,MD

CONTACT

0577-586305; a.m.digiacomo@ao-siena.toscana.it

Michele Maio, PhD,MD

CONTACT

0577-586335; mmaiocro@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 22, 2015
• First Posted: June 2, 2015
• Study Start: December 1, 2012
• Primary Completion: January 1, 2018
• Study Completion: January 1, 2020
• Last Updated: June 2, 2015

Record last verified: 2015-05

Locations

IT (11)