Brentuximab vedotin (SGN-35) as salvage therapy for males with advanced and platinum-resistant germ-cell tumors. An open label, single group, Phase 2 trial

Phase 1

• Conditions: Patients with histologically-confirmed germ-cell cancer with exclusive or prevalent CD30-positive embryonal carcinoma component; MedDRA version: 14.1Level: PTClassification code 10061378Term: Testicular germ cell cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2012-004508-36-IT
• Lead Sponsor: Fondazione Michelangelo - Avanzamento dello studio e cura dei tumori

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-03-07
• Last Update Posted: 26 February 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Male
• Target Recruitment: 24

Inclusion Criteria

1.Age = 18 years
2.Male patients, even if surgically sterilized, (i.e., status post vasectomy) agree to practice effective barrier contraception during the entire study period and through 6 months after the last dose of study drug, or agrees to completely abstain from heterosexual intercourse.
3.Confirmation of GCT histology based on pathologic review at Fondazione INT Milan.
4.Presence of a CD30-positive embryonal carcinoma component. It should be assessed on either research biopsy immediately prior to start of brentuximab (preferably) or on archival tissue of the most recent post-chemotherapy viable residual (in the absence of easily accessible disease or in presence of clinical contraindications to biopsy).
5.Unequivocal progression of measurable disease (measurable disease will consist of abnormalities on 2-dimensional imaging or raised tumor markers) as documented by either:
a.Tumor biopsy of new, growing or unresectable lesions demonstrating viable non-teratomatous GCT (enrollment on this study for consolidation treatment after resection of viable GCT is not allowed).
b.Increasing or abnormally elevated serum tumor markers (HCG or AFP). Increasing LDH alone does not constitute progressive disease.
6.A minimum of 2 and a maximum of 3 platinum-based chemotherapy lines for metastatic disease (enrollment will take place either as 3rd or 4th line of treatment). EXCEPT for primary mediastinal GCTs where failure of first-line chemotherapy ( 2nd line setting) is accepted.
7.First-line therapy should consist of at least 3 cycles of cisplatin-based chemotherapy.
8.Prior single, tandem or triple high-dose chemotherapy course given as front-line or salvage therapy is allowed.
9.Recovery from prior surgery.

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 12
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 12

Exclusion Criteria

1.Failure to meet any of the above inclusion criteria.
2.Less than 2 prior lines of cisplatin-based chemotherapy (including one cisplatin-based chemotherapy line followed by high-dose therapy). Except for primary mediastinal GCTs where less than 2 prior lines of cisplatin-based chemotherapy (2nd line setting) is accepted.
3.Prior Treatment with any of the following anti-cancer therapies:
4.radiation therapy, surgery or tumor embolization are allowed with a washout period of 14 days prior to enrolment OR
5.chemotherapy, immunotherapy, biologic therapy, investigational therapy or hormonal therapy are allowed with a washout period of 14 days or five half-lives of a drug (whichever is longer) prior to enrolment.
6.Patients with late-relapse (defined as relapse occurring after at least 2 years from the date of completion of the last chemotherapy regimen) whose disease is completely surgically resectable (and for whom initial surgical extirpation is recommended) are ineligible. Patients with unresectable late disease relapse are eligible.

Study & Design

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

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the activity of single-agent brentuximab vedotin in a population of patients with platinum-resistant GCT.<br>Primary Endpoint: <br>- Overall response-rate (RR) as defined by CR+PRm-+PRm+. <br>;Secondary Objective: To evaluate the safety and tolerability of the study drug. <br>To evaluate further efficacy parameters<br><br>Secondary Endpoints:<br>-Safety and tolerability (according to Common terminology Criteria for Adverse Events – CTCAE - v.4.03). <br>-<br>-3-month Progression-free survival (PFS).<br>-Overall survival (OS).<br>-Quality of life assessment.<br>-Correlation of 18FDG-PET/CT response with STM and CT response and PFS.<br>;Primary end point(s): -Overall response-rate (RR) as defined by CR+PRm -+PRm+. ;Timepoint(s) of evaluation of this end point: Duration of follow up will be described by descriptive statistics such as median and interquartile range.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): -Safety and tolerability (according to Common terminology Criteria for Adverse Events – CTCAE - v.4.03). <br>-<br>-3-month Progression-free survival (PFS).<br>-Overall survival (OS).<br>-Quality of life assessment.<br>-Correlation of 18FDG-PET/CT response with STM and CT response and PFS.<br>;Timepoint(s) of evaluation of this end point: 3-month for the PFS