MedPath

ivolumab in pre-treated advanced germ cells tumours patients with Mismatch repair deficiency

Phase 1
Conditions
patients with platinum resistant Mismatch Repair deficient germinal cells tumours
MedDRA version: 21.1Level: PTClassification code 10061184Term: Germ cell cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]
Registration Number
EUCTR2017-000589-31-IT
Lead Sponsor
SOCIETà CAMPANA DI IMMUNOTERAPIA ONCOLOGICA
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
ot Recruiting
Sex
Male
Target Recruitment
38
Inclusion Criteria

1)Signed and dated IRB/IEC-approved Informed Consent;
2)Male patients> 18 years;
3)Life expectancy > 3 months;
4)Performance status (ECOG) = 2;
5)Histological or clinical diagnosis of GCTs;
6)Availability of archival tissue (paraffine block or at least 10 unstained slides) to evaluate the PD-L1 status, which is positive (expression = 1 percent of tumour cells) or negative;
7)Microsatellite instability (MSI) and/or DNA repair defects including mismatch-repair gene deficiency (MMR-).
8)Either gonadal or extragonadal tumour primary;
9)Failure of = 2 prior chemotherapy regimens for metastatic GCT disease (1-2 cycles PEB or 1 cycle carboplatinum AUC7 given in the adjuvant setting for clinical stage I disease will not be counted as prior lines);¿
10)Brain metastases: patients who present with brain metastases as the sole site of disease relapse/progression are not allowed to enter the study. Otherwise, patients with massive systemic spread with brain metastases will be allowed to enrol into the study, provided that they will not undergo concomitant brain radiation, brain surgery or they are judged to be at high-risk of bleeding (high-volume metastases with haemorrhagic spots resulting at either CT or ¿MRI scan of the brain);
11)Patients must have recovered from toxicity related to prior therapy to at least grade 1 (defined by v.CTCAE 4.0);
12)Patients must not have had major surgery, radiation therapy, chemotherapy, biologic therapy (including any investigational agents), or hormonal therapy (other than replacement), within 3 weeks prior to entering the study;
13)Patients must have adequate organ and marrow function (as defined below). Patients must have returned to baseline or grade 1 from any acute toxicity related to prior therapy. Laboratory test must be performed within 3 days before date of treatment
1.Absolute neutrophil count = 1,500/mm;
2.Hemoglobin = 9 g/dL;
3.Platelets = 100,000/mm;
4.Total bilirubin = 1.5 x institutional upper limit of normal (ULN), except for patients affected by Gilbert’s syndrome;
5.AST(SGOT)/ALT(SGPT) = 3 x institutional ULN (5x if LFT elevations due to liver metastases);
14)Male who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception starting with the first dose of study therapy through 7 months after the last dose of study therapy.

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 19
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 19

Exclusion Criteria

1)Patients with symptomatic brain metastases should be excluded from this clinical trial because of their poor prognosis and because of the steroids administration. However, patients who have had treatment for their brain metastases and whose brain metastatic disease status has remained stable for at least 3 months without steroids may be enrolled at the discretion of the investigator;
2)Patients with a diagnosis of immunodeficiency or is receiving steroid therapy and/or immunosuppressive therapy within 7 days before the treatment starting;
3)Patients with a diagnosis of active autoimmune disease requiring systemic treatment within the past 90 days, or a documented history of clinically severe autoimmune disease, that requires systemic steroids and/or immunosuppressive agents. Patients with vitiligo or resolved asthma/atopy or stable hypothyroidism, will not be excluded from the trial;
4)Major surgery, other than diagnostic surgery, within 4 weeks prior to treatment;
5)Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy;
6)Previous (within the last 5 years) or current malignancies at other sites, except for basal cell or squamous cell skin cancer that have undergone potentially curative treatment;
7)Current enrolment in or participation in another therapeutic clinical trial within 4 weeks before the first dose of treatment;
8)Patients with uncontrolled or significant cardiovascular disease within 12 months, unstable angina within 6 months, NYHA Class III, poorly controlled hypertension, ongoing symptomatic cardiac dysrhythmias and uncontrolled atrial fibrillation;
9)Known HIV infection;
10)Patients with a diagnosis of interstitial lung disease or non-infectious pneumonitis;
11)Patient with a diagnosis of active hepatitis B (HBsAg reactive) or C (HCV-RNA qualitative is detected);
12)Patients who received a live vaccine one month before the treatment starting;
13)Patients who received treatment with mAb within one month before the first dose of trial treatment;
14)Patients who have had radiotherapy or chemotherapy within 14 days of the first dose of trial treatment.

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Secondary Outcome Measures
NameTimeMethod
© Copyright 2025. All Rights Reserved by MedPath