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)
• Enrollment: 1
• Location: 1
• Arm: 1
• Actual Duration (Months): 32.6
• Patients Per Site Per Month: 0

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 Disease	Intervention/Treatment	Phase
Germ Cell Tumor	Drug: Brentuximab Vedotin; Drug: Bevacizumab	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

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 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

	Site	City	State	Country	Postal Code
1	University of Minnesota	Minneapolis	Minnesota	United States	55455

Sponsors and Collaborators

• Masonic Cancer Center, University of Minnesota

Investigators

• Principal Investigator: Shilpa Gupta, University of Minnesota

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - May 10, 2017

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: GCT
• Additional relevant MeSH terms: Neoplasms, Germ Cell and Embryonal; Bevacizumab; Brentuximab Vedotin

Study Results

Participant Flow

Arm/Group Title	Brentuximab Vedotin & Bevacizumab
Arm/Group Description	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. 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
STARTED	1
COMPLETED	1
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Brentuximab Vedotin & Bevacizumab
Arm/Group Description	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
Overall Participants	1
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

Title	Disease Response Rate as Defined by the RECIST 1.1 Criteria, Integrated With Tumor Marker Response.
Description	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.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Brentuximab Vedotin & Bevacizumab
Arm/Group Description	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
Measure Participants	1
Baseline	1 100%
Complete Remission	0 0%
Progressive disease	0 0%

2. Secondary Outcome

Title	Number of Participants Experiencing Progression Free Survival
Description	Incidence of Progression-free survival - Number of patients who were alive and did not have disease progression
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Brentuximab Vedotin & Bevacizumab
Arm/Group Description	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
Measure Participants	1
Count of Participants [Participants]	0 0%

3. Secondary Outcome

Title	Number of Participants Who Were Alive at 2 Years - Overall Survival
Description	Number of participants who were alive at 2 years (Overall survival)
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Brentuximab Vedotin & Bevacizumab
Arm/Group Description	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
Measure Participants	1
Count of Participants [Participants]	0 0%

4. Secondary Outcome

Title	Number of Participants Experiencing Adverse Events (AE) and Severe Adverse Events (SAE)
Description	Safety/ toxicity of brentuximab vedotin, measured by incidence of AEs/SAEs
Time Frame	2 Years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Brentuximab Vedotin & Bevacizumab
Arm/Group Description	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
Measure Participants	1
Count of Participants [Participants]	1 100%

Adverse Events

Time Frame	2 years
Arm/Group Title	Brentuximab Vedotin & Bevacizumab
Arm/Group Description	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
All Cause Mortality
	Brentuximab Vedotin & Bevacizumab
	Affected / at Risk (%)	# Events
Total	1/1 (100%)
Serious Adverse Events
	Brentuximab Vedotin & Bevacizumab
	Affected / at Risk (%)	# Events
Total	0/1 (0%)
Other (Not Including Serious) Adverse Events
	Brentuximab Vedotin & Bevacizumab
	Affected / at Risk (%)	# Events
Total	1/1 (100%)
Gastrointestinal disorders
Enterocolitis	1/1 (100%)	2
Vomiting	1/1 (100%)	2
General disorders
Chills	1/1 (100%)	2
Nervous system disorders
Dizziness	1/1 (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.