Brentuximab Vedotin in Relapsed/Refractory Germ Cell Tumors

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Brief Title

Brentuximab Vedotin in Relapsed/Refractory Germ Cell Tumors

Official Title

A Multicenter Phase II Study of Brentuximab Vedotin in Relapsed/Refractory Germ Cell Tumors

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.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Objective Response (Percent of Patients With Complete Response or Partial Response)

Secondary Outcome

 Progression Free Survival

Condition

Germ Cell Tumors

Intervention

Brentuximab Vedotin

Study Arms / Comparison Groups

 CD30 positive
Description:  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.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

18

Start Date

March 9, 2016

Completion Date

January 23, 2019

Primary Completion Date

November 13, 2018

Eligibility Criteria

        Inclusion Criteria

        Subject must meet all of the following applicable inclusion criteria to participate in this
        study:

          1. Age ≥ 18 years at the time of informed consent.

          2. 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.

          3. 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:

               1. A >25% increase in the products of perpendicular diameters of measurable tumor
                  masses during prior therapy which are not amenable to surgical resection.

               2. The presence of new tumors which are not amenable to surgical resection.

               3. 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.

          4. Patients must have evidence of recurrent or metastatic carcinoma by one or more of the
             following:

             i) 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.

          5. 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.

          6. 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.

          7. 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.

          8. Patients with ECOG performance status of 0-2.

          9. Adequate organ and marrow function as defined below:

               1. Hemoglobin ≥ 8 g/dL

               2. Absolute neutrophil count ≥ 1,000/mm3

               3. Platelet count ≥ 75,000/mm3

               4. Total bilirubin ≤ 1.5 × ULN except patients with documented Gilbert's syndrome (≤
                  3 × ULN)

               5. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN;
                  for patients with hepatic metastases, ALT and AST ≤ 5 × ULN

               6. Calculated creatinine clearance ≥ 30 mL/min as determined by the Cockcroft-Gault
                  equation.

         10. 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).

         11. 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.

         12. 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.

        Exclusion Criteria

        Subjects meeting any of the criteria below may not participate in the study:

          1. Patients with pure seminoma.

          2. Patients with pure teratoma.

          3. Chemotherapy within 2 weeks of initiating study treatment. There is no maximum
             allowable number of previous therapies.

          4. 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.

          5. Radiation within 2 weeks of starting study treatment.

          6. ≥ Grade 3 neuropathy at the time of enrollment.

          7. Pregnancy or breast-feeding.

          8. Previous treatment with any anti-CD30 directed therapy.
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Costantine Albany, MD, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT02689219

Organization ID

IUSCC-0568


Responsible Party

Sponsor-Investigator

Study Sponsor

Nabil Adra


Study Sponsor

Costantine Albany, MD, Principal Investigator, Indiana University School of Medicine, Indiana University Simon Cancer Center


Verification Date

December 2019