Brentuximab Vedotin (SGN-35) as Salvage Treatment for CD30-positive Germ Cell Tumors

NCT ID: NCT01851200

Last Updated: 2018-02-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 9 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-05-31
• Study Completion Date: 2017-09-30

Brief Summary

The purpose of the study is to assess the activity of Brentuximab vedotin in refractory germ cell tumors.

Detailed Description

Complete responses with third-line or later salvage chemotherapy (CT) for germ cell tumors (GCT) range 0% to 10% and are usually short-lived and nearly all patients (pts) progressing after multiple courses or high-dose CT will ultimately die from progressive disease.

Cluster of Differentiation antigen-30 (CD30) is expressed by untreated embryonal carcinoma (ECA) thus lending support to a rationale for a targeted approach. The investigators retrospectively re-assessed ECA to strongly retain CD30 staining in most cases (>70%), even after multiple courses or high-dose CT. Moreover, a negative prognostic value of CD30 expression by residuals after CT, particularly in the salvage setting, was set. Brentuximab vedotin is an antibody-drug conjugate consisting of the chimeric anti-CD30 antibody chemically conjugated to an antitubulin synthetic analog (MMAE).

Proof of activity will provide rationale for developing first-line chemo-immunotherapy or maintenance immunotherapy for selected high-risk pts. The primary objective of the study will be the activity of Brentuximab vedotin in refractory GCT. Secondary objectives will include safety and survival.

24 pts with biopsy-proven CD30 positive GCT will receive intravenous Brentuximab vedotin at the dose of 1.8 mg/Kg every 3 weeks until disease progression or onset of unacceptable toxicity. Further eligibility requirements will include failure of 2 or 3 platinum-based CT (prior high-dose CT is allowed). All pts will undergo measurement of serum tumor markers, a computed tomography and a positron emission tomography (PET) scan every weeks. An optimal Simon's 2-stage design will be applied. The primary endpoint is the objective response-rate (ORR). An ORR of 5% is not promising, while a 25% rate will be promising. In stage 1, 9 evaluable patients will be accrued. The type I and II error are both set at 10%.

Additional post-treatment tissue will be available for pts undergoing surgery in the treatment time-course. Tissue array blocks will be constructed from samples of all pts. Assessment will include mutational analysis of most-frequently mutated genes. Two serum aliquots will be collected at baseline and during/end of treatment to assess circulating CD30.

Conditions

Germ Cell Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Brentuximab Vedotin

Intravenous Brentuximab Vedotin at the dose of 1.8 mg/Kg every 3 weeks until disease progression or onset of unacceptable toxicity

Group Type: EXPERIMENTAL

Brentuximab Vedotin

Intervention Type: DRUG

Intravenous Brentuximab Vedotin at the dose of 1.8 mg/Kg every 3 weeks until disease progression or onset of unacceptable toxicity

Interventions

Brentuximab Vedotin

Intravenous Brentuximab Vedotin at the dose of 1.8 mg/Kg every 3 weeks until disease progression or onset of unacceptable toxicity

Intervention Type: DRUG

Other Intervention Names

SGN-35; Adcetris

Eligibility Criteria

Inclusion Criteria

• Age of at least 18 years.
• Confirmation of germ cell tumor histology based on pathologic review at the study site.
• Presence of a CD30 positive embryonal carcinoma component.
• Unequivocal progression of measurable disease.
• A minimum of 2 and a maximum of 3 platinum-based chemotherapy lines for metastatic disease EXCEPT for primary mediastinal germ cell tumors where failure of first-line chemotherapy only is accepted.
• Prior high dose chemotherapy with hematopoietic stem cell rescue is allowed.

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

OTHER

Sponsor Role: collaborator

Millennium Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: collaborator

Fondazione Michelangelo

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Alessandro M Gianni, MD

Role: STUDY_CHAIR

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Roberto Salvioni, MD

Role: STUDY_CHAIR

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Andrea Necchi, MD

Role: PRINCIPAL_INVESTIGATOR

Fondazione IRCCS Istituto Nazionale dei Tumori, Milan

Locations

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, Mi, Italy

Countries

Italy

Related Links

http://www.fondazionemichelangelo.org

Web site of the study Sponsor

Other Identifiers

2012-004508-36

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

FM-12-GCT01

Identifier Type: -

Identifier Source: org_study_id