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Trial record 4 of 133 for:    SGN-35

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

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ClinicalTrials.gov Identifier: NCT01851200
Recruitment Status : Completed
First Posted : May 10, 2013
Last Update Posted : February 7, 2018
Sponsor:
Collaborators:
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Millennium Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Fondazione Michelangelo

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

Condition or disease Intervention/treatment Phase
Germ Cell Cancer Drug: Brentuximab Vedotin Phase 2

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.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 9 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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.
Actual Study Start Date : May 2013
Actual Primary Completion Date : August 2017
Actual Study Completion Date : September 2017

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: Brentuximab Vedotin
Intravenous Brentuximab Vedotin at the dose of 1.8 mg/Kg every 3 weeks until disease progression or onset of unacceptable toxicity
Drug: Brentuximab Vedotin
Intravenous Brentuximab Vedotin at the dose of 1.8 mg/Kg every 3 weeks until disease progression or onset of unacceptable toxicity
Other Names:
  • SGN-35
  • Adcetris



Primary Outcome Measures :
  1. 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. [ Time Frame: Six weeks after the first administration of the study drug. ]

Secondary Outcome Measures :
  1. Progression-Free Survival [ Time Frame: 3 months after the initiation of study treatment ]
  2. Overall Survival [ Time Frame: Six months after the initiation of study treatment ]
  3. Incidence of adverse events related to the study drug [ Time Frame: Six weeks after the initiation of the study drug and every 6 weeks thereafter up to 16 weeks. ]

Other Outcome Measures:
  1. Metabolic response to Brentuximab Vedotin measured by means of a Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (FDG-PET/CT) scan. [ Time Frame: Six weeks after the first administration of the study drug. ]


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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01851200


Locations
Italy
Fondazione IRCCS Istituto Nazionale dei Tumori
Milano, Mi, Italy, 20133
Sponsors and Collaborators
Fondazione Michelangelo
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Millennium Pharmaceuticals, Inc.
Investigators
Study Chair: Alessandro M Gianni, MD Fondazione IRCCS Istituto Nazionale dei Tumori
Study Chair: Roberto Salvioni, MD Fondazione IRCCS Istituto Nazionale dei Tumori
Principal Investigator: Andrea Necchi, MD Fondazione IRCCS Istituto Nazionale dei Tumori, Milan

Additional Information:
Responsible Party: Fondazione Michelangelo
ClinicalTrials.gov Identifier: NCT01851200     History of Changes
Other Study ID Numbers: FM-12-GCT01
2012-004508-36 ( EudraCT Number )
First Posted: May 10, 2013    Key Record Dates
Last Update Posted: February 7, 2018
Last Verified: April 2016

Keywords provided by Fondazione Michelangelo:
Testicular neoplasms
Germ Cell cancers
Embryonal Carcinoma
Metastatic
Brentuximab Vedotin

Additional relevant MeSH terms:
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs