An open label, randomized, phase 2 study of the anti-Programmed Death-Ligand 1 (PD-L1) Durvalumab, alone or in combination with Tremelimumab, in patients with advanced and relapsed germ cell tumors
- Conditions
- Advanced and relapsed germ cell tumorsMedDRA version: 21.1Level: PTClassification code 10068971Term: Germ cell cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2016-001688-35-IT
- Lead Sponsor
- FONDAZIONE IRCCS ISTITUTO NAZIONALE DEI TUMORI
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 120
1.Written informed consent and any locally-required authorization (e.g., HIPAA in the USA, EU Data Privacy Directive in the EU) obtained from the subject prior to performing any protocol-related procedures, including screening evaluations
2.Age > 18 years at time of study entry
3.Male or female gender
4.Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
5.Life expectancy of > 12 weeks
6.Adequate normal organ and marrow function
7.Histological or clinical diagnosis of GCT.
8.Availability of archival tumor samples for local assessment (by immunohistochemistry) of PD-L1 expression.
9.Either gonadal or extragonadal tumor primary.
10.Failure of =2 prior chemotherapy regimens for metastatic disease (1-2 cycles PEB or 1 cycle carboplatin AUC7 given in the adjuvant setting for clinical stage I disease will not be counted as prior lines).
11.Failure of high-dose chemotherapy will be allowed.
12.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 metastatic disease including brain metastases will be allowed provided that they have been irradiated, are stable from at least 4 weeks, and a wash-out period from steroids has occurred (28 days).
13.Female subjects must either be of non-reproductive potential (ie, post-menopausal by history: =60 years old and no menses for ¿1 year without an alternative medical cause; OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of bilateral oophorectomy) or must have a negative serum pregnancy test upon study entry.
14.Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
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 100
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20
1.Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
3.Participation in another clinical study with an investigational product during the last 3 months
4.Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab or an anti-CTLA4, including tremelimumab
5.History of another primary malignancy except for:
•Malignancy treated with curative intent and with no known active disease =5 years before the first dose of study drug and of low potential risk for recurrence
•Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
6.Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) =28 days prior to the first dose of study drug
7.Mean QT interval corrected for heart rate (QTc) =470 ms
8.Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab or tremelimumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid
9.Any unresolved toxicity (>CTCAE grade 2) from previous anti-cancer therapy.
10.Any prior Grade =3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE >Grade 1
11.Active or prior documented autoimmune disease within the past 2 years NOTE: Subjects with vitiligo, Grave’s disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded.
12.Active or prior documented inflammatory bowel disease
13.History of primary immunodeficiency
14.History of allogeneic organ transplant
15.History of hypersensitivity to durvalumab or any excipient
16.Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses including any subject known to have evidence of acute or chronic hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent
17.Known history of previous clinical diagnosis of tuberculosis and active tuberculosis.
18.History of leptomeningeal carcinomatosis
19.Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving durvalumab or tremelimumab
22.Symptomatic or uncontrolled brain metastases requiring concurrent treatment, inclusive of but not limited to surgery, radiation and/or corticosteroids.
23.Subjects with uncontrolled seizures.
24.Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 180 days after the last dose of durvalumab + tremelimumab combination therapy or 90 days after the last dose of durvalumab monotherapy, whichever is the longer time period.
25.Known allergy or hypersensitivity to IP or any excipient.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Primary end point(s): Complete response plus partial response with negative marker;Timepoint(s) of evaluation of this end point: at 3 months ;Main Objective: To evaluate the activity and efficacy of durvalumab and durvalumab+tremelimumab in a population of extensively pre-treated patients with GCT.;Secondary Objective: To evaluate the safety and tolerability of the study drug. <br>To evaluate the Quality of Life changes during treatment.<br>To evaluate the ability of metabolic imaging (by 18Fluoodeoxyglucose positron emission tomography [18FDG-PET/CT]) to evaluate th activity of the study drug(s).<br>
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Safety ( based on CTCAE v 4.03 ); PD-L1 expression and response /PFS/OS; PFS; OS; quality of life asessment;Timepoint(s) of evaluation of this end point: 42 months; at the end of study; 3 months; at 6 months; at the end of the study