Germ Cell Cancer Clinical Trial
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.
The purpose of the study is to assess the activity of Brentuximab vedotin in refractory germ cell tumors.
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.
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