Germ Cell CancerPhase 2NCT01851200
Brentuximab Vedotin (SGN-35) as Salvage Treatment for CD30-positive Germ Cell Tumors
A Phase 2 study testing Brentuximab Vedotin in people with Germ Cell Cancer, run by Fondazione Michelangelo at 1 site in Italy.
Trial summary
The purpose of the study is to assess the activity of Brentuximab vedotin in refractory germ cell tumors. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Germ Cell Cancer
- What is being tested?
- Brentuximab Vedotin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteItaly
- Study dates
- May 2013to Sep 2017
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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
- Being tested
- Brentuximab Vedotin
- Keywords
- Testicular neoplasms, Germ Cell cancers, Embryonal Carcinoma, Metastatic, Brentuximab Vedotin
- Medical subject headings
- Neoplasms, Germ Cell and Embryonal, Testicular Neoplasms, Carcinoma, Embryonal, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Brentuximab VedotinDrug
Also called SGN-35, Adcetris
Intravenous Brentuximab Vedotin at the dose of 1.8 mg/Kg every 3 weeks until disease progression or onset of unacceptable toxicity
| Study group | Role | What they receive |
|---|---|---|
| Brentuximab Vedotin | Experimental | Intravenous Brentuximab Vedotin at the dose of 1.8 mg/Kg every 3 weeks until disease progression or onset of unacceptable toxicity Receives: Drug: Brentuximab Vedotin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Six weeks after the first administration of the study drug.
Secondary outcomes (3)
Progression-Free Survival
Measured: 3 months after the initiation of study treatment
Overall Survival
Measured: Six months after the initiation of study treatment
Incidence of adverse events related to the study drug
Measured: Six weeks after the initiation of the study drug and every 6 weeks thereafter up to 16 weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 May 2013 (estimated)
- Study startMay 2013
- Primary completionAug 2017
- Study completionSep 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Germ Cell CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fondazione Michelangelo
- Sponsor type
- University, hospital or other
- Collaborators
- Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Millennium Pharmaceuticals, Inc.
- Responsible party
- Sponsor
- Investigators
- Alessandro M Gianni, MD, Study chair, Fondazione IRCCS Istituto Nazionale dei Tumori, MilanoRoberto Salvioni, MD, Study chair, Fondazione IRCCS Istituto Nazionale dei Tumori, MilanoAndrea Necchi, MD, Principal investigator, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01851200
- Sponsor's protocol ID
- FM-12-GCT01
- Other IDs
- 2012-004508-36
- Status last verified
- Apr 2016
- First submitted
- 20 Apr 2013
- Last updated
- 7 Feb 2018
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 7 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT01851200
- Acronym / sponsor ID
- FM-12-GCT01
- Conditions
- Germ Cell Cancer
- Keywords
- Testicular neoplasms, Germ Cell cancers, Embryonal Carcinoma, Metastatic, Brentuximab Vedotin
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Fondazione MichelangeloUniversity, hospital or other
- Collaborators
- Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Millennium Pharmaceuticals, Inc.
- Study start
- May 2013 (actual)
- Primary completion
- Aug 2017 (actual)
- Study completion
- Sep 2017 (actual)
- First posted
- 10 May 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Brentuximab Vedotin | Experimental | Drug: Brentuximab VedotinIntravenous Brentuximab Vedotin at the dose of 1.8 mg/Kg every 3 weeks until disease progression or onset of unacceptable toxicity |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (2 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Brentuximab VedotinAlso: SGN-35, AdcetrisIntravenous Brentuximab Vedotin at the dose of 1.8 mg/Kg every 3 weeks until disease progression or onset of unacceptable toxicity | Drug | Brentuximab Vedotin |
Primary outcome
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.
3 secondary outcomes
Progression-Free Survival
Time frame: 3 months after the initiation of study treatment
Overall Survival
Time frame: Six months after the initiation of study treatment
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Feb 2018.
- Web site of the study SponsorLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alessandro M Gianni, MD study chair
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Roberto Salvioni, MD study chair
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Andrea Necchi, MD principal investigator
Fondazione IRCCS Istituto Nazionale dei Tumori, Milan
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Brentuximab Vedotin in people with Germ Cell Cancer, run by Fondazione Michelangelo at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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. (time frame: Six weeks after the first administration of the study drug.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Feb 2018.