Clinical trial NCT01851200: Brentuximab Vedotin (SGN-35) as Salvage Treatment for CD30-positive Germ Cell Tumors
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Germ Cell Cancer
Keywords: Testicular neoplasms
Germ Cell cancers
Embryonal Carcinoma
Metastatic
Brentuximab Vedotin
Lead sponsor: Fondazione Michelangelo
Sponsor class: OTHER
Collaborators: name: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
name: Millennium Pharmaceuticals, Inc.
First posted: 2013-05-10
Enrollment: 9
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Exclusion Criteria:

* Failure to meet any of the above inclusion criteria.
* 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.

Primary outcomes:
measure: The number of objective responses (partial and complete responses) according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 integrated with response of serum tumor markers.
timeFrame: Six weeks after the first administration of the study drug.
Secondary outcomes:
measure: Progression-Free Survival
timeFrame: 3 months after the initiation of study treatment
measure: Overall Survival
timeFrame: Six months after the initiation of study treatment
measure: Incidence of adverse events related to the study drug
timeFrame: Six weeks after the initiation of the study drug and every 6 weeks thereafter up to 16 weeks.
Other outcomes:
measure: Metabolic response to Brentuximab Vedotin measured by means of a Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (FDG-PET/CT) scan.
timeFrame: Six weeks after the first administration of the study drug.
Locations:
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
state: Mi
Study officials:
affiliation: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
name: Alessandro M Gianni, MD
role: STUDY_CHAIR
affiliation: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
name: Roberto Salvioni, MD
role: STUDY_CHAIR
affiliation: Fondazione IRCCS Istituto Nazionale dei Tumori, Milan
name: Andrea Necchi, MD
role: PRINCIPAL_INVESTIGATOR
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