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

Sponsor
Masonic Cancer Center, University of Minnesota (Other)
Overall Status
Terminated
CT.gov ID
NCT02988843
Collaborator
(none)
1
Enrollment
1
Location
1
Arm
32.6
Actual Duration (Months)
0
Patients Per Site Per Month

Study Details

Study Description

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 DiseaseIntervention/TreatmentPhase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
1 participants
Allocation:
N/A
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 :
Mar 29, 2017
Actual Primary Completion Date :
Dec 15, 2019
Actual Study Completion Date :
Dec 15, 2019

Arms and Interventions

ArmIntervention/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 Names:
  • ADCETRIS
  • Drug: Bevacizumab
    15 mg/kg every 21 days
    Other Names:
  • Avastin
  • Outcome Measures

    Primary Outcome Measures

    1. Disease Response Rate as Defined by the RECIST 1.1 Criteria, Integrated With Tumor Marker Response. [1 year]

      Changes in the largest diameter (unidimensional measurement) of the tumor lesions and the shortest diameter in the case of malignant lymph nodes are used in the RECIST criteria. In addition to CT scan to assess for disease evaluation, whole body bone scans will be done for patients with known or suspected bone metastases to assess for bone lesions.

    Secondary Outcome Measures

    1. Number of Participants Experiencing Progression Free Survival [2 years]

      Incidence of Progression-free survival - Number of patients who were alive and did not have disease progression

    2. Number of Participants Who Were Alive at 2 Years - Overall Survival [2 years]

      Number of participants who were alive at 2 years (Overall survival)

    3. Number of Participants Experiencing Adverse Events (AE) and Severe Adverse Events (SAE) [2 Years]

      Safety/ toxicity of brentuximab vedotin, measured by incidence of AEs/SAEs

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Male
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1University of MinnesotaMinneapolisMinnesotaUnited States55455

    Sponsors and Collaborators

    • Masonic Cancer Center, University of Minnesota

    Investigators

    • Principal Investigator: Shilpa Gupta, University of Minnesota

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Masonic Cancer Center, University of Minnesota
    ClinicalTrials.gov Identifier:
    NCT02988843
    Other Study ID Numbers:
    • 2015LS190
    First Posted:
    Dec 9, 2016
    Last Update Posted:
    Dec 10, 2020
    Last Verified:
    Nov 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    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
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group TitleBrentuximab Vedotin & Bevacizumab
    Arm/Group DescriptionBevacizumab 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. 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) Bevacizumab: 15 mg/kg every 21 days
    Period Title: Overall Study
    STARTED1
    COMPLETED1
    NOT COMPLETED0

    Baseline Characteristics

    Arm/Group TitleBrentuximab Vedotin & Bevacizumab
    Arm/Group DescriptionBevacizumab 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
    Overall Participants1
    Age (Count of Participants)
    <=18 years
    0
    0%
    Between 18 and 65 years
    1
    100%
    >=65 years
    0
    0%
    Sex: Female, Male (Count of Participants)
    Female
    0
    0%
    Male
    1
    100%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    0
    0%
    Not Hispanic or Latino
    1
    100%
    Unknown or Not Reported
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    Asian
    0
    0%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    Black or African American
    0
    0%
    White
    1
    100%
    More than one race
    0
    0%
    Unknown or Not Reported
    0
    0%
    Region of Enrollment (participants) [Number]
    United States
    1
    100%

    Outcome Measures

    1. Primary Outcome
    TitleDisease Response Rate as Defined by the RECIST 1.1 Criteria, Integrated With Tumor Marker Response.
    DescriptionChanges in the largest diameter (unidimensional measurement) of the tumor lesions and the shortest diameter in the case of malignant lymph nodes are used in the RECIST criteria. In addition to CT scan to assess for disease evaluation, whole body bone scans will be done for patients with known or suspected bone metastases to assess for bone lesions.
    Time Frame1 year

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleBrentuximab Vedotin & Bevacizumab
    Arm/Group DescriptionBevacizumab 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
    Measure Participants1
    Baseline
    1
    100%
    Complete Remission
    0
    0%
    Progressive disease
    0
    0%
    2. Secondary Outcome
    TitleNumber of Participants Experiencing Progression Free Survival
    DescriptionIncidence of Progression-free survival - Number of patients who were alive and did not have disease progression
    Time Frame2 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleBrentuximab Vedotin & Bevacizumab
    Arm/Group DescriptionBevacizumab 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
    Measure Participants1
    Count of Participants [Participants]
    0
    0%
    3. Secondary Outcome
    TitleNumber of Participants Who Were Alive at 2 Years - Overall Survival
    DescriptionNumber of participants who were alive at 2 years (Overall survival)
    Time Frame2 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleBrentuximab Vedotin & Bevacizumab
    Arm/Group DescriptionBevacizumab 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
    Measure Participants1
    Count of Participants [Participants]
    0
    0%
    4. Secondary Outcome
    TitleNumber of Participants Experiencing Adverse Events (AE) and Severe Adverse Events (SAE)
    DescriptionSafety/ toxicity of brentuximab vedotin, measured by incidence of AEs/SAEs
    Time Frame2 Years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleBrentuximab Vedotin & Bevacizumab
    Arm/Group DescriptionBevacizumab 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
    Measure Participants1
    Count of Participants [Participants]
    1
    100%

    Adverse Events

    Time Frame2 years
    Adverse Event Reporting Description
    Arm/Group TitleBrentuximab Vedotin & Bevacizumab
    Arm/Group DescriptionBevacizumab 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
    All Cause Mortality
    Brentuximab Vedotin & Bevacizumab
    Affected / at Risk (%)# Events
    Total1/1 (100%)
    Serious Adverse Events
    Brentuximab Vedotin & Bevacizumab
    Affected / at Risk (%)# Events
    Total0/1 (0%)
    Other (Not Including Serious) Adverse Events
    Brentuximab Vedotin & Bevacizumab
    Affected / at Risk (%)# Events
    Total1/1 (100%)
    Gastrointestinal disorders
    Enterocolitis1/1 (100%) 2
    Vomiting1/1 (100%) 2
    General disorders
    Chills1/1 (100%) 2
    Nervous system disorders
    Dizziness1/1 (100%) 3

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/TitleDr. Shilpa Gupta
    OrganizationMasonic Cancer Center, University of Minnesota
    Phone612 624 0123
    Emailguptash@umn.edu
    Responsible Party:
    Masonic Cancer Center, University of Minnesota
    ClinicalTrials.gov Identifier:
    NCT02988843
    Other Study ID Numbers:
    • 2015LS190
    First Posted:
    Dec 9, 2016
    Last Update Posted:
    Dec 10, 2020
    Last Verified:
    Nov 1, 2020