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Brentuximab Vedotin in Relapsed/Refractory Germ Cell Tumors

Phase 2
Terminated
Conditions
Germ Cell Tumors
Testis Cancer
Embryonal Carcinoma
Testicular Cancer
Nonseminomatous Germ Cell Tumor
Interventions
Registration Number
NCT02689219
Lead Sponsor
Nabil Adra
Brief Summary

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

1. To determine the progression free survival in patients with relapsed/ refractory NSGCT treated with brentuximab vedotin.

2. To determine the overall survival of patients with relapsed/ refractory NSGCT treated with brentuximab vedotin.

3. 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.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
18
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
CD30 negative/unknownBrentuximab 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 positiveBrentuximab 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.
Primary Outcome Measures
NameTimeMethod
Objective Response (Percent of Patients With Complete Response or Partial Response)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.

Secondary Outcome Measures
NameTimeMethod
Number of Patients With Treatment Related Adverse Events Grade 3 or AboveUp to 2 years

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.

Overall SurvivalUp to 2 years

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.

Progression Free SurvivalUp to 2 years

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.

Trial Locations

Locations (4)

Indiana University Health Hospital

🇺🇸

Indianapolis, Indiana, United States

USC/Norris Comprehensive Cancer Center

🇺🇸

Los Angeles, California, United States

Indiana University Health Melvin and Bren Simon Cancer Center

🇺🇸

Indianapolis, Indiana, United States

Memorial Sloan Kettering Cancer Center

🇺🇸

New York, New York, United States

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