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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

Tracking Information
First Submitted Date  ICMJE December 1, 2016
First Posted Date  ICMJE December 9, 2016
Last Update Posted Date September 26, 2018
Actual Study Start Date  ICMJE March 29, 2017
Estimated Primary Completion Date February 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 7, 2016)
Disease response rate as defined by the RECIST 1.1 criteria, integrated with tumor marker response. [ Time Frame: 1 year ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02988843 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 26, 2017)
  • Progression free survival [ Time Frame: 2 years ]
  • Overall survival [ Time Frame: 2 years ]
  • Safety/ toxicity of brentuximab vedotin, measured by incidence of AEs/SAEs [ Time Frame: 2 Years ]
Original Secondary Outcome Measures  ICMJE
 (submitted: December 7, 2016)
  • Progression free survival [ Time Frame: 1 year ]
  • Overall survival [ Time Frame: 1 year ]
Current Other Outcome Measures  ICMJE Not Provided
Original Other Outcome Measures  ICMJE Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Brentuximab Vedotin And Bevacizumab In Refractory CD-30 Positive Germ Cell Tumors
Official Title  ICMJE Phase II Study of Brentuximab Vedotin and Bevacizumab in Men With Refractory CD-30 Positive Germ Cell Tumors
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Germ Cell Tumor
Intervention  ICMJE
  • 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
Study Arms 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.
Interventions:
  • Drug: Brentuximab Vedotin
  • Drug: Bevacizumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Suspended
Estimated Enrollment  ICMJE
 (submitted: December 7, 2016)
21
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date February 2021
Estimated Primary Completion Date February 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender
Sexes Eligible for Study: Male
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02988843
Other Study ID Numbers  ICMJE 2015LS190
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement
Plan to Share IPD: No
Responsible Party Masonic Cancer Center, University of Minnesota
Study Sponsor  ICMJE Masonic Cancer Center, University of Minnesota
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Shilpa Gupta University of Minnesota - Clinical and Translational Science Institute
PRS Account Masonic Cancer Center, University of Minnesota
Verification Date September 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP