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Study of Brentuximab Vedotin And Bevacizumab In Refractory CD-30 Positive Germ Cell Tumors

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ClinicalTrials.gov Identifier: NCT02988843
Recruitment Status : Suspended (Funding Unavailable)
First Posted : December 9, 2016
Last Update Posted : September 26, 2018
Sponsor:
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota

Brief Summary:
This is a multi-center phase II study of brentuximab vedotin in combination with bevacizumab for the treatment of refractory CD-30+ germ cell tumors (GCT) after disease progression on imaging and/or tumor marker progression documented by serially rising alpha-fetoprotein (AFP) or beta human chorionic gonadotropin (bHCG) measured on at least 2 consecutive visits and determined by treating physician to be clinically significant. Patients unable to receive 2nd line of platinum-based chemotherapy due to toxicity or refusal would also be eligible.

Condition or disease Intervention/treatment Phase
Germ Cell Tumor Drug: Brentuximab Vedotin Drug: Bevacizumab Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 21 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of Brentuximab Vedotin and Bevacizumab in Men With Refractory CD-30 Positive Germ Cell Tumors
Actual Study Start Date : March 29, 2017
Estimated Primary Completion Date : February 2021
Estimated Study Completion Date : February 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Brentuximab Vedotin & Bevacizumab
  • Bevacizumab will be administered at a dose of 15 mg/kg IV every 21 days; over 90 minutes during 1st infusion, over 60 minutes as 2nd infusion and over 30 minutes for subsequent infusions if prior infusions well tolerated.
  • Brentuximab vedotin will be administered first at 1.8 mg/kg (maximum dose of 180 mg) IV over 30 minutes every 21 days.
Drug: Brentuximab Vedotin
Dose level 1: 1.8 mg/kg every 21 days (up to 180 mg) Dose level -1 :1.2 mg/kg every 21 days ( up to 120 mg)
Other Name: ADCETRIS

Drug: Bevacizumab
15 mg/kg every 21 days
Other Name: Avastin




Primary Outcome Measures :
  1. Disease response rate as defined by the RECIST 1.1 criteria, integrated with tumor marker response. [ Time Frame: 1 year ]

Secondary Outcome Measures :
  1. Progression free survival [ Time Frame: 2 years ]
  2. Overall survival [ Time Frame: 2 years ]
  3. Safety/ toxicity of brentuximab vedotin, measured by incidence of AEs/SAEs [ Time Frame: 2 Years ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male, ≥ 18 years of age
  • Diagnosis of CD-30 positive germ cell tumor. CD30 expression will be tested by immunohistochemistry (IHC) in archival or fresh tumor tissue as is routinely done for diagnosis.
  • Disease progression on imaging or tumor marker progression (clinical significance of tumor marker progression to be decided per the discretion of treating physician) after at least 2 lines of platinum-based chemotherapies unless patient is ineligible for further platinum based chemotherapy or refuses 2nd line platinum based chemotherapy due to toxicity. For primary mediastinal germ cell tumors, failure of first-line chemotherapy will be accepted. Prior high dose chemotherapy with hematopoietic stem cell rescue is allowed. Prior treatment with bevacizumab is allowed.
  • At least 3 weeks should have elapsed since the last treatment (e.g. chemotherapy, targeted small molecule therapy, immunotherapy or radiation) and must have recovered to grade 1 or better from the acute effects of prior therapy.
  • Presence of measurable disease according to RECIST 1.1
  • ECOG performance status 0 or 1
  • Adequate marrow and organ function within 28 days prior to study registration as defined below:

    • Leukocytes > 3,000/µL
    • ANC > 1500/µL
    • Hemoglobin ≥ 9 g/dL, Note: Blood transfusion will be allowed for patients with hemoglobin < 9 g/dl and G-CSF is allowed for neutropenic patients at time of enrollment.
    • Platelets > 100,000/mm3
    • Creatinine: ≤3mg/dl OR if serum creatinine > 3 mg/dl, estimated GFR >30 mL/min/1.73m2
    • INR: <1.5 x institutional upper limit of normal OR < 3 if on warfarin or other anticoagulants. There should be no evidence of active bleeding while on anticoagulants.
    • Total bilirubin: ≤ 2 x institutional upper limit of normal (ULN)
    • SGOT (AST) or SGPT (ALT): < 3 x institutional upper limit of normal (< 5 x ULN if liver metastases present)
    • Proteinuria: If patient has proteinuria, it should be <2+ (< 100 mg/dl or per institutional guidelines). If proteinuria is 2+ or greater (≥ 100 mg/dl per institutional guidelines), patients should undergo a 24- hour urine collection and 24 hour urinary protein should be less than < 2 grams.
  • Sexually active men with partners of women of childbearing potential must agree to practice effective methods of contraception during the study and for 6 months after the last treatment
  • Provide voluntary written consent and HIPAA authorization for release of personal health information, approved by an Institutional Review Board/Independent Ethics Committee (IRB/IEC)

Exclusion Criteria:

  • Prior treatment with Brentuximab Vedotin.
  • Known active brain metastases and or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided brain metastases are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to study registration. This exception does not include carcinomatous meningitis, which is excluded regardless of clinical stability.
  • History of blood clots, pulmonary embolism, or deep vein thrombosis in previous 6 months unless controlled by anticoagulant treatment
  • Known history of HIV
  • Known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected)
  • Received a live vaccine within 1 week prior to the first dose of study treatment
  • Has active autoimmune disease that required systemic treatment with use of disease modifying agents, corticosteroids or immunosuppressive drugs
  • Any clinically significant active infection that requires systemic treatment at the time of enrollment.
  • Known allergy to bevacizumab or brentuximab vedotin or any of its excipients
  • Patients who have congestive heart failure (NYHA Class III or IV), unstable angina, sustained ventricular tachycardia, ventricular fibrillation, clinically significant bradycardia, advanced heart block or a history of acute myocardial infarction (MI) within 6 months of study registration
  • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess in previous 6 months
  • Prior major surgery within the previous 28 days of study registration and/or presence of any non-healing wound, fracture, or ulcer.
  • Use of an investigational agent within the previous 28 days of study registration.
  • Poorly controlled hypertension [defined as systolic blood pressure (SBP) of ≥150 mmHg and/or diastolic blood pressure (DBP) of ≥ 90mmHg]. Note: Initiation or adjustment of antihypertensive medication(s) is permitted prior to study registration
  • Arterial thromboembolic events, including transient ischemic attack (TIA), cerebrovascular accident (CVA), unstable angina, or MI within 6 months of study registration
  • History of posterior reversible encephalopathy syndrome
  • Other malignancies unless the patient is considered to be disease-free and has completed therapy for the malignancy > than 6 months prior to study entry
  • Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures
  • Concurrent use of rifampin or ketoconazole

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02988843


Locations
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United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55455
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
Investigators
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Principal Investigator: Shilpa Gupta University of Minnesota - Clinical and Translational Science Institute

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Responsible Party: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT02988843     History of Changes
Other Study ID Numbers: 2015LS190
First Posted: December 9, 2016    Key Record Dates
Last Update Posted: September 26, 2018
Last Verified: September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Masonic Cancer Center, University of Minnesota:
GCT

Additional relevant MeSH terms:
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Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Bevacizumab
Antibodies, Monoclonal
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Immunologic Factors