Germ Cell TumorsPhase 2NCT02689219
Brentuximab Vedotin in Relapsed/Refractory Germ Cell Tumors
A Phase 2 study testing Brentuximab Vedotin in people with Germ Cell Tumors and Testis Cancer, run by Nabil Adra at 4 sites in United States.
Trial summary
This is a Phase II study to evaluate the activity of brentuximab vedotin in relapsed/refractory non-seminomatous germ cell tumors (NSGCT). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Germ Cell Tumors, Testis Cancer, Testicular 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
- 18 participants
- Where
- 4 sitesUnited States
- Study dates
- 9 Mar 2016to 23 Jan 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subject must meet all of the following applicable inclusion criteria to participate in this study:
- Age ≥ 18 years at the time of informed consent.
- Patients with histologically or serologically confirmed relapsed/refractory non-seminoma germ cell tumor, (i.e., embryonal carcinoma, choriocarcinoma, or yolk sac tumors) including female GCT and primary mediastinal NSGCT.
- Patients must have progressed after prior high dose chemotherapy (HDCT) treatment, been deemed not to be a candidate for high dose chemotherapy or refused high-dose chemotherapy, and be considered incurable by other standard therapies including further chemotherapy or surgery. There is no maximum allowable number of previous therapies.
- "Failure" of prior therapy is defined as:
- A >25% increase in the products of perpendicular diameters of measurable tumor masses during prior therapy which are not amenable to surgical resection.
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- The presence of new tumors which are not amenable to surgical resection.
- An increase in AFP or beta-hCG (two separate determinations at least one week apart are required if rising tumor markers are the only evidence of failure).
- NOTE: Patients with clinically growing "teratoma" (normal declining tumor markers and radiographic or clinical progression) should be considered for surgery.
- Patients must have evidence of recurrent or metastatic carcinoma by one or more of the following:
- The appearance of metastatic disease by standard imaging techniques ii) The appearance of rising serum tumor marker, AFP or beta-hCG NOTE: If a rising tumor marker is the only evidence of progressive disease, at least 2 consecutive rising values at least one week apart are needed. Patients with only evidence of disease is rising tumor marker AFP and beta-hCG will be provided alternate causes of increased serum levels of these markers are not present, such as cross reaction with luteinizing Hormone (LH) (that can be tested if needed by testosterone suppression of LH), hepatitis, use of marijuana or second primary tumor, etc.
- Patients with primary medistinal non seminomatous germ cell tumor are eligible if they have received first line platinum based chemotherapy and their recurrence is not amenable to surgical resection based on the treating physician expert opinion.
- Patients with late relapse (>2 years) of non seminomatous germ cell tumors are eligible if they have received first line platinum based chemotherapy and their recurrence is not amenable to surgical resection based on the treating physician expert opinion.
- Patients with brain metastases are allowed onto the study as long as patients have completed their treatment for brain metastasis, no longer require corticosteroids, and are asymptomatic. Subjects with neurological symptoms should undergo a head CT scan or brain MRI to exclude brain metastasis, at the discretion of the treating physician.
- Patients with ECOG performance status of 0-2.
- Adequate organ and marrow function as defined below:
- Hemoglobin ≥ 8 g/dL
- Absolute neutrophil count ≥ 1,000/mm3
- Platelet count ≥ 75,000/mm3
- Total bilirubin ≤ 1.5 × ULN except patients with documented Gilbert's syndrome (≤ 3 × ULN)
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN; for patients with hepatic metastases, ALT and AST ≤ 5 × ULN
- Calculated creatinine clearance ≥ 30 mL/min as determined by the Cockcroft-Gault equation.
- Patients who are willing and able to comply with the protocol and study procedures including willingness to undergo tumor biopsy for tumor cells before therapy to assess for CD30 status (unless archival tumor tissue from orchiectomy or other previous sample is not obtainable despite efforts to do so and a fresh tumor biopsy is not feasible).
- Females of childbearing potential must not be pregnant or breast-feeding. Male and female patients of reproductive potential must agree to use two forms of highly effective contraception from the screening visit through 28 days after the last dose of study drug. Acceptable forms of effective contraception include:
- Oral, injected or implanted hormonal methods of contraception.
- Placement of an intrauterine device (IUD) or intrauterine system (IUS).
- Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository.
- Male sterilization (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate).
- True abstinence: When this is in line with the preferred and usual lifestyle of the subject. [Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.] Pregnancy tests for females of childbearing potential are required; must be serum at screening and the post treatment safety assessment visit. A positive urine pregnancy test must be confirmed by a serum pregnancy test and a pelvic US since some NSGCT may secrete beta-hCG and cause a false positive pregnancy. A pelvic US does not need to be repeated with each cycle unless the treating physician thinks it is necessary to do so.
- Potential subject must have the ability to understand (as judged by the treating physician) and willingness to provide written informed consent and HIPAA authorization for release of personal health information.
- NOTE: HIPAA authorization may be included in the informed consent or obtained separately. Written informed consent must be obtained from a potential subject prior to the conduct of any study-specific procedures.
Who cannot join
- Subjects meeting any of the criteria below may not participate in the study:
- Patients with pure seminoma.
- Patients with pure teratoma.
- Chemotherapy within 2 weeks of initiating study treatment. There is no maximum allowable number of previous therapies.
- Major surgery within 3 weeks of starting study treatment. There is no minimum time requirement for minor procedures such as biopsy or vascular access placement.
- Radiation within 2 weeks of starting study treatment.
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- ≥ Grade 3 neuropathy at the time of enrollment.
- Pregnancy or breast-feeding.
- Previous treatment with any anti-CD30 directed therapy.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Indiana University Health Hospital
Indianapolis, Indiana, 46202
Indiana University Health Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, 46202
USC/Norris Comprehensive Cancer Center
Los Angeles, California, 90033
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
About this study
Official title: A Multicenter Phase II Study of Brentuximab Vedotin in Relapsed/Refractory Germ Cell Tumors
This is a Phase II study to evaluate the activity of brentuximab vedotin in relapsed/refractory non-seminomatous germ cell tumors (NSGCT).
Read the detailed description
Primary Objective To determine the anti-tumor efficacy of brentuximab vedotin in relapsed/ refractory NSGCT.
Secondary Objectives
- To determine the progression free survival in patients with relapsed/ refractory NSGCT treated with brentuximab vedotin.
- To determine the overall survival of patients with relapsed/ refractory NSGCT treated with brentuximab vedotin.
- To determine the safety and tolerability of brentuximab vedotin in this patient population.
Eligible patients will be divided into two cohorts, those who are CD30 positive and those who are CD30 negative/unknown. Both groups will be treated similarly and in parallel but analyzed separately. CD30 status may be unknown in the unlikely case of tumor-marker-only relapse or when a fresh tumor biopsy is not feasible, and archival tumor tissue is not obtainable despite efforts to do so. These patients will be included in the CD30 negative cohort for analysis purposes, since statistically NSGCT are more likely to be CD30 negative. The number of such patients with unknown CD30 status should not exceed 5 patients.
Eligible patients will be treated with brentuximab vedotin at 1.8 mg/kg IV every 3 weeks (maximum dose of 180 mg) indefinitely until disease progression, unacceptable toxicity, or study closure.Eligible patients with grade 2 peripheral neuropathy at enrollment will be treated with brentuximab vedotin at 1.2 mg/kg IV every 3 weeks (maximum dose of 180 mg) indefinitely until disease progression, unacceptable toxicity, or study closure. Response to treatment will be assessed clinically with history, physical exam and tumor markers measurement (BHCG and AFP) on day 1 of each cycle and with CT scans after cycle 2, 4, and every 4 cycles thereafter while receiving treatment.
- Conditions
- Germ Cell Tumors, Testis Cancer, Testicular Cancer, Embryonal Carcinoma, Nonseminomatous Germ Cell Tumor
- Being tested
- Brentuximab Vedotin
- Keywords
- Antigens, CD30, Embryonal Germ Cell Tumors
- Medical subject headings
- Neoplasms, Germ Cell and Embryonal, Testicular Neoplasms, Carcinoma, Embryonal, Nonseminomatous germ cell tumor
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
Both cohorts will be treated similarly and in parallel but analyzed separately.
| Study group | Role | What they receive |
|---|---|---|
| CD30 positive | Experimental | Brentuximab vedotin, 1.8 mg/kg (1.2 mg/kg in patients with grade 2 peripheral neuropathy at enrollment) will be administered by IV infusion given over approximately 30 minutes on Day 1 of each 21-day cycle. Receives: Drug: Brentuximab Vedotin |
| CD30 negative/unknown | Experimental | Brentuximab vedotin, 1.8 mg/kg (1.2 mg/kg in patients with grade 2 peripheral neuropathy at enrollment) will be administered by IV infusion given over approximately 30 minutes on Day 1 of each 21-day cycle. Receives: Drug: Brentuximab Vedotin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response (Percent of Patients With Complete Response or Partial Response)
Measured by RECIST v1.1 and tumor markers (AFP and BhCG). CR - disappearance of all target lesions and normalization of serum tumor markers for at least 4 weeks. When only evidence of disease is elevated serum tumor markers, then values must fall below the upper limit of normal for the assay and remain at that level for at least 4 weeks. PR - at least a 30% decrease in the sum of the diameters of target lesions compared to the baseline sum diameters for at least 2 measurements 1 month apart with the serum markers as stable/decreasing. When only evidence of disease is elevated serum tumor markers, then values must fall >=90% below baseline pretreatment levels for BhCG or 50% decrease below baseline pretreatment levels for AFP and persist for 6 weeks. If both tumor markers are elevated and one falls below 90% the other should fall at least below 50% of baseline pretreatment levels.The percent of patients with objective response and its 95% exact confidence interval will be provided.
Measured: Up to 1 year
Secondary outcomes (3)
Progression Free Survival
Duration of time from the start of treatment to time of documented progression or death. Patients who did not progress or die were censored on their last evaluation date. Kaplan-Meier methods will be used and the median and 95% confidence intervals will be calculated.
Measured: Up to 2 years
Overall Survival
Duration of time from the start of treatment to time of death due to any causes. Patients who did not die were censored on their last known alive date. Kaplan-Meier methods will be used and the median and 95% confidence intervals will be calculated.
Measured: Up to 2 years
Number of Patients With Treatment Related Adverse Events Grade 3 or Above
Number of unique patients who had a treatment related (possible, probable or definite) adverse event with grade >= 3 using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Measured: Up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Feb 2016 (estimated)
- Study start9 Mar 2016
- Primary completion13 Nov 2018
- Study completion23 Jan 2019
Why it stopped: lack of funding/ benefit
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Germ Cell TumorsStudies 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nabil Adra
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Nabil Adra, Indiana University
- Investigators
- Costantine Albany, MD, Principal investigator, Indiana University School of Medicine, Indiana University Simon Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02689219
- Sponsor's protocol ID
- IUSCC-0568
- Status last verified
- Dec 2019
- First submitted
- 12 Feb 2016
- Last updated
- 10 Dec 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter Phase II Study of Brentuximab Vedotin in Relapsed/Refractory Germ Cell Tumors
- ClinicalTrials.gov ID
- NCT02689219
- Acronym / sponsor ID
- IUSCC-0568
- Conditions
- Germ Cell Tumors, Testis Cancer, Testicular Cancer, Embryonal Carcinoma, Nonseminomatous Germ Cell Tumor
- Keywords
- Antigens, CD30, Embryonal Germ Cell Tumors
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: lack of funding/ benefit
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Nabil AdraUniversity, hospital or other
- Study start
- 9 Mar 2016 (actual)
- Primary completion
- 13 Nov 2018 (actual)
- Study completion
- 23 Jan 2019 (actual)
- First posted
- 23 Feb 2016 (estimated)
- Results
- Posted 26 Nov 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase II study to evaluate the activity of brentuximab vedotin in relapsed/refractory non-seminomatous germ cell tumors (NSGCT).
Detailed description
Primary Objective To determine the anti-tumor efficacy of brentuximab vedotin in relapsed/ refractory NSGCT.
Secondary Objectives
- To determine the progression free survival in patients with relapsed/ refractory NSGCT treated with brentuximab vedotin.
- To determine the overall survival of patients with relapsed/ refractory NSGCT treated with brentuximab vedotin.
- To determine the safety and tolerability of brentuximab vedotin in this patient population.
Eligible patients will be divided into two cohorts, those who are CD30 positive and those who are CD30 negative/unknown. Both groups will be treated similarly and in parallel but analyzed separately. CD30 status may be unknown in the unlikely case of tumor-marker-only relapse or when a fresh tumor biopsy is not feasible, and archival tumor tissue is not obtainable despite efforts to do so. These patients will be included in the CD30 negative cohort for analysis purposes, since statistically NSGCT are more likely to be CD30 negative. The number of such patients with unknown CD30 status should not exceed 5 patients.
Eligible patients will be treated with brentuximab vedotin at 1.8 mg/kg IV every 3 weeks (maximum dose of 180 mg) indefinitely until disease progression, unacceptable toxicity, or study closure.Eligible patients with grade 2 peripheral neuropathy at enrollment will be treated with brentuximab vedotin at 1.2 mg/kg IV every 3 weeks (maximum dose of 180 mg) indefinitely until disease progression, unacceptable toxicity, or study closure. Response to treatment will be assessed clinically with history, physical exam and tumor markers measurement (BHCG and AFP) on day 1 of each cycle and with CT scans after cycle 2, 4, and every 4 cycles thereafter while receiving treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CD30 positive | Experimental | Drug: Brentuximab VedotinBrentuximab vedotin, 1.8 mg/kg (1.2 mg/kg in patients with grade 2 peripheral neuropathy at enrollment) will be administered by IV infusion given over approximately 30 minutes on Day 1 of each 21-day cycle. |
| CD30 negative/unknown | Experimental | Drug: Brentuximab VedotinBrentuximab vedotin, 1.8 mg/kg (1.2 mg/kg in patients with grade 2 peripheral neuropathy at enrollment) will be administered by IV infusion given over approximately 30 minutes on Day 1 of each 21-day cycle. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (31 listed)
- Subject must meet all of the following applicable inclusion criteria to participate in this study:
- Age ≥ 18 years at the time of informed consent.
- Patients with histologically or serologically confirmed relapsed/refractory non-seminoma germ cell tumor, (i.e., embryonal carcinoma, choriocarcinoma, or yolk sac tumors) including female GCT and primary mediastinal NSGCT.
- Patients must have progressed after prior high dose chemotherapy (HDCT) treatment, been deemed not to be a candidate for high dose chemotherapy or refused high-dose chemotherapy, and be considered incurable by other standard therapies including further chemotherapy or surgery. There is no maximum allowable number of previous therapies.
- NOTE: Patients with clinically growing "teratoma" (normal declining tumor markers and radiographic or clinical progression) should be considered for surgery.
Key exclusion criteria (9 listed)
- Patients with pure seminoma.
- Patients with pure teratoma.
- Chemotherapy within 2 weeks of initiating study treatment. There is no maximum allowable number of previous therapies.
- Major surgery within 3 weeks of starting study treatment. There is no minimum time requirement for minor procedures such as biopsy or vascular access placement.
- Radiation within 2 weeks of starting study treatment.
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-35Both cohorts will be treated similarly and in parallel but analyzed separately. | Drug | CD30 negative/unknown, CD30 positive |
Primary outcome
Objective Response (Percent of Patients With Complete Response or Partial Response)
Time frame: Up to 1 year
Measured by RECIST v1.1 and tumor markers (AFP and BhCG). CR - disappearance of all target lesions and normalization of serum tumor markers for at least 4 weeks. When only evidence of disease is elevated serum tumor markers, then values must fall below the upper limit of normal for the assay and remain at that level for at least 4 weeks. PR - at least a 30% decrease in the sum of the diameters of target lesions compared to the baseline sum diameters for at least 2 measurements 1 month apart with the serum markers as stable/decreasing. When only evidence of disease is elevated serum tumor markers, then values must fall >=90% below baseline pretreatment levels for BhCG or 50% decrease below baseline pretreatment levels for AFP and persist for 6 weeks. If both tumor markers are elevated and one falls below 90% the other should fall at least below 50% of baseline pretreatment levels.The percent of patients with objective response and its 95% exact confidence interval will be provided.
3 secondary outcomes
Progression Free Survival
Time frame: Up to 2 years
Overall Survival
Time frame: Up to 2 years
Number of Patients With Treatment Related Adverse Events Grade 3 or Above
Time frame: Up to 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Dec 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Costantine Albany, MD principal investigator
Indiana University School of Medicine, Indiana University Simon Cancer Center
4 sites 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 Tumors and Testis Cancer, run by Nabil Adra at 4 sites in United States.
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 31 inclusion and 9 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: stopped early, as of the sponsor's last update on 10 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. 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?
Yes. Results are posted in the registry (first posted 26 Nov 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Objective Response (Percent of Patients With Complete Response or Partial Response) (time frame: Up to 1 year). 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 10 Dec 2019.