Ipilimumab in combination with Nivolumab followed by Nivolumab monotherapy in patients with unresectable or oligometastatic melanoma.
- Conditions
- Patients with histologically or cytologically confirmed AJCC (8th ed.) Stage IIIB -IV resectable melanoma.MedDRA version: 21.1Level: LLTClassification code 10053571Term: MelanomaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-002172-40-IT
- Lead Sponsor
- ISTITUTO EUROPEO DI ONCOLOGIA
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 35
Patients must have histologically or cytologically confirmed 8th ed. AJCC Stage IIIB/C/D
or Stage IV oligometastatic resectable melanoma. Patients with cutaneous, mucosal, acral,
ocular or unknown primary melanomas are eligible for enrollment. Oligometastatic
melanoma is defined as three or fewer areas of resectable disease excluding central
nervous system and bone involvement. In case of involvement of three areas, one must be
superficial (cutaneous-subcutaneous). Resectable tumors are defined as having no
significant vascular, neural or bony involvement. A multidisciplinary discussion within
surgical oncologists, medical oncologists, and radiologist will assess if disease is
resectable.
· Signed Written Informed Consent.
· Patients must be willing and able to comply with scheduled visits, treatment schedule,
laboratory tests and all protocol procedures.
· Males and Females, ages =18 years of age.
· Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
· Have measurable disease based on RECIST 1.1.
· Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor
lesion at baseline and at the time points specified in the Study Procedure Tables.
· Known BRAF V600 mutation status as determined by local institutional standard. All
BRAF statuses (BRAF wild type or BRAF 600 mutation positive) are eligible.
· Patients who have been previously treated in the adjuvant setting for melanoma will be
eligible for treatment after a 28 day washout period.
· Patients must be medically fit enough to undergo surgery as determined by the treating
medical and surgical oncology team.
· Demonstrate adequate organ function as defined below: Hematologic Absolute neutrophil
count (ANC) >/= 1.5 X 10^9/L; Hemoglobin >/= 9.5 g/dL Platelets >/= 100 X 10^9/L
PT/INR and PTT >1.5 X ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%) AST and
ALT Albumin /=2.5 g/dL Renal Creatinine OR Calculated creatinine
clearance OR 24-hour urine creatinine clearance /= 50 mL/min >/= 50
mL/min.
· Women are eligible to participate if: non-childbearing potential defined as pre-menopausal
females with a documented tubal ligation or hysterectomy; or postmenopausal defined as
12 months of spontaneous amenorrhea
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 30
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5
oncological therapies or other concomitant experimental oncologic treatments.
B. Major surgery within the previous 3 weeks
C. Cerebral, leptomeningee or bone metastases
D. Pregnancy or lactation.
E. Concomitant pathologies that increase, in the opinion of investigators, the risk associated with
the Participation in the study, the administration of the treatment or interfering with the
interprettazioen of Results
F. Active oncological pathologies arising in the two years preceding enlistment except
Pre-existing diagnosis of melanoma and treatable neoplasia and apparently treated with local
therapies,
G. Patients with autoimmune diseases known or suspected, with the exception of vitiligo, diabetes
mellitus of type I, hypothyroidism resulting from autoimmune diseases and requiring substitution
therapy, Psoriasis that does not require systemic therapy, or conditions that you expect a flare to
Cause of external factors
H. Corticosteroid therapy (> 10 mg/day of prednisone or equivalent) or other treatment
Immunosuppressants within 14 days of administration of treatment
I. Topical or inhalatory steroids and replacement therapy for adrenal insufficiency with > 10
mg/day of prednisone or equivalents are allowed in the absence of an active autoimmune disease
J. Previous anti-PD-1, anti-PD-L1 or anti-CTLA-4 antibody therapy.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: evaluation of efficacy in terms of pathological complete response rates;Secondary Objective: Feasibility and safety. Identification of outcome-related biomarkers;Primary end point(s): pathological complete response rates after surgery.;Timepoint(s) of evaluation of this end point: after surgery.
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Rates of grade 3-4 AE rates (immune related or not) of neoadjuvant and adjuvant regimen and overall AE rates<br>· Overall Response Rate (ORR), according to RECIST 1.1 criteria and overall pathological response rate<br>· Overall Survival (OS)<br>· Health related quality of life (HRQoL);Timepoint(s) of evaluation of this end point: every cycle/ end of treatment