Brentuximab Vedotin in Treating Patients with Relapsed or Refractory Germ Cell Tumors
This phase II trial studies how well brentuximab vedotin works in treating patients with germ cell tumors that have come back or do not respond to treatment. Monoclonal antibodies, such as brentuximab vedotin, may interfere with the ability of cancer cells to grow and spread.
- Patients with histologically or serologically confirmed relapsed/refractory non-seminoma germ cell tumor, (i.e., embryonal carcinoma, choriocarcinoma, or yolk sac tumors) including female germ cell tumors (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 ** The presence of new tumors which are not amenable to surgical resection ** An increase in AFP or beta-human chorionic gonadotropin (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 * 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 mediastinal 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’s 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’s 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 computed tomography (CT) scan or brain magnetic resonance imaging (MRI) to exclude brain metastasis, at the discretion of the treating physician
- Patients with Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- Hemoglobin >= 8 g/dL
- Absolute neutrophil count >= 1,000/mm^3
- Platelet count >= 75,000/mm^3
- Total bilirubin =< 1.5 x upper limit of normal (ULN) except patients with documented Gilbert’s syndrome (=< 3 x ULN)
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x ULN; for patients with hepatic metastases, ALT and AST =< 5 x 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 unless patient is practicing true abstinence; acceptable forms of effective contraception include: * Oral, injected or implanted hormonal methods of contraception * Tubal ligation * 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 (defined as complete retrograde ejaculation or 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 ultrasound (US); 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 Health Insurance Portability and Accountability Act (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
- 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
- >= grade 3 neuropathy at the time of enrollment
- Pregnancy or breast-feeding
- Previous treatment with any anti-CD30 directed therapy
Locations & Contacts
Trial Objectives and Outline
I. To determine the anti-tumor efficacy of brentuximab vedotin in relapsed/refractory non-seminoma germ cell tumors (NSGCT).
I. To determine the progression free survival in patients with relapsed/refractory NSGCT treated with brentuximab vedotin.
II. To determine the overall survival of patients with relapsed/refractory NSGCT treated with brentuximab vedotin.
III. To determine the safety and tolerability of brentuximab vedotin in this patient population.
I. To characterize the intensity and localization (cell wall versus [vs.] cytoplasmic) of CD30 staining among tumors from patients with relapsed or refractory NSGCT enrolling on the study.
II. To correlate the intensity and localization of tumor staining for CD30 with objective response and progression-free survival for patients enrolling on the study.
Patients receive brentuximab vedotin intravenously (IV) over 30 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 2 months for 1 year.
Trial Phase & Type
Indiana University / Melvin and Bren Simon Cancer Center
Secondary IDs NCI-2017-00271
Clinicaltrials.gov ID NCT02689219