A randomized, Phase III study of Fotemustine versus the Combination of Fotemustine and Ipilimumab in Patients with Metastatic Melanoma with brain metastasis

Phase 1

• Conditions: Subjects (men and women) 18 years old presenting with Stage IV melanoma with presence of brain metastasis; MedDRA version: 14.1Level: PTClassification code 10025671Term: Malignant melanoma stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2012-004301-27-IT
• Lead Sponsor: FONDAZIONE NIBIT

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2012-10-30
• Last Update Posted: 12 March 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 160

Inclusion Criteria

1) Signed Written Informed Consent
a) Willing and able to give written informed consent.
2) Target Population
a) Histologic diagnosis of malignant melanoma;
b) Stage IV melanoma;
c) No prior therapy for advanced (unresectable Stage III or Stage IV) disease;
d) No previous systemic corticosteroid therapy within 7 days; steroids for symptoms related to brain disease, developed during treatment are allowed;
e) Prior adjuvant treatment with IFN or other immunotherapy allowed with exception of anti-CTLA-4;
f) 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;
g) 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;
h) Have a full set of baseline (i.e., Screening) digital images of cutaneous lesions and radiographic images, including, but not limited to: MRI of brain, CT of chest, abdomen, pelvis and soft tissue. All images must be of adequate quality as detailed in Section 6.4.1 of the protocol;
i) Life expectancy 12 weeks;
j) ECOG performance status of 0 or 1;
k) Required values for initial laboratory tests:
i) WBC >=3500/uL
ii) ANC >=2000/uL
iii) Platelets >=100 x 103/uL
iv) Hemoglobin >=9 g/dL
v) Creatinine <=2.5 x ULN
vi) AST <=2.5 x ULN for patients without liver metastasis
<= 5 x ULN for patients with liver metastasis
vii) Bilirubin <= 1.5 x ULN for patients without liver metastasis
<= 3 x ULN for patients with liver metastasis
< 3.0 mg/mL for patients with Gilbert’s Syndrome
Negative screening tests for HIV, Hepatitis B, and Hepatitis C. If positive results are not indicative of true active or chronic infection, the patient can enter the study after discussion and agreement between the Investigator and clinical monitor.
3) Age and Sex
a) 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.
WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not postmenopausal. Post menopause is defined as:
(1) Amenorrhea >=12 consecutive months without another cause or
(2) For women with irregular menstrual periods and on hormone replacement therapy (HRT), a documented serum follicle stimulating hormone (FSH) level > 35 mIU/mL
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 160
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1) Sex and Reproductive Status
a) 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;
b) Women who are pregnant or breastfeeding;
c) Women with a positive pregnancy test on enrollment or prior to investigational product administration;
d) Sexually active fertile men not using effective birth control if their partners are WOCBP.
2) Target Disease Exceptions
a) 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;
b) Primary ocular or mucosal melanoma.
3) Medical History and Concurrent Diseases
a) Symptomatic brain metastases requiring immediate local intervention (radiotherapy (RT) and/or surgery);
b) Leptominingeal involvement by disease;
c) Autoimmune disease: Patients with a documented history of Inflammatory Bowel Disease, including ulcerative colitis and Crohn’s disease are excluded from this study as are patients with a documented history of symptomatic autoimmune disease (eg, rheumatoid arthritis, systemic progressive sclerosis [scleroderma], Systemic Lupus Erythematosus, autoimmune vasculitis [eg, Wegener’s Granulomatosis] and autoimmune hepatitis. Subjects with motor neuropathy considered of autoimmune origin (eg, Guillain-Barre Syndrom) are also excluded from this study;
d) 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.
4) Prohibited Treatments and/or Therapies
a) 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 (except as described in Sections 5.5.1 and 5.5.2); other investigational anti-cancer therapies; or chronic use of systemic corticosteroids (used in the management of cancer or non-cancer-related illnesses);
b) Previous treatment with other investigational products, including cancer immunotherapy, within 30 days;
c) Prior treatment with anti-CTLA-4 and/or fotemustine.
5) Other Exclusion Criteria
a) Prisoners or subjects who are involuntarily incarcerated;
b) Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified