Brentuximab Vedotin in Treating Patients With CD30+ Malignant Mesothelioma That Cannot Be Removed by Surgery
Primary Purpose
CD30-Positive Neoplastic Cells Present, Malignant Mesothelioma
Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Brentuximab Vedotin
Laboratory Biomarker Analysis
Sponsored by
About this trial
This is an interventional treatment trial for CD30-Positive Neoplastic Cells Present
Eligibility Criteria
Inclusion Criteria:
- Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care
- Female subject is either: a. post-menopausal for at least one year before the screening visit; or b. surgically sterilized; or c. willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study and at least 6 months after the last dose of brentuximab vedotin
- Male subject, even if surgically sterilized (i.e., status postvasectomy), agrees to use an acceptable barrier method for contraception (condom with a spermicidal agent), or completely abstain from heterosexual intercourse during the entire study treatment period through 6 months after the last dose of brentuximab vedotin
- Absolute neutrophil count (ANC) > 1500/mm^3
- Platelets > 100,000/mm^3
- Hemoglobin (Hgb) > 8.5 g/dL
- Total bilirubin =< 1.5 x upper limit of normal (ULN)
- Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 3 x ULN; AST and/or ALT may be up to 5 X ULN if with known liver metastases (mets)
- Calculated creatinine clearance must be >= 30 mL/minute
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Pathologic diagnosis of malignant mesothelioma (any primary site is acceptable, any histology is acceptable)
- Have unresectable malignant mesothelioma (any histology)
- Positive CD30+ immunohistochemical expression
- Any line of prior therapy - patients may be chemo-naive or chemo-refractory (any line)
- Patients must have measurable disease by modified Response Evaluation Criteria in Solid Tumors (RECIST) or RECIST; examinations for assessment of measurable disease must have been completed within 28 days prior to registration
Exclusion Criteria:
- Radiation therapy to more than 25% of the bone marrow; whole pelvic radiation is considered to be over 25%
- Prior allogeneic bone marrow or organ transplantation
- Female subject who is pregnant or breast-feeding; confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (B-hCG) pregnancy test result obtained during screening; pregnancy testing is not required for post-menopausal or surgically sterilized women
- Patient has received other investigational drugs with 14 days before enrollment
- Serious medical or psychiatric illness likely to interfere with participation in this clinical study
- No prior history of malignancy within 2 years, unless cured of a skin cancer or a stage I-III solid tumor; no prior hematologic malignancy within 3 years
- Known hypersensitivity to brentuximab vedotin components
- Persons who are incarcerated at time of enrollment (e.g., prisoners) or likely to become incarcerated during the study
Sites / Locations
- M D Anderson Cancer CenterRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Treatment (brentuximab vedotin)
Arm Description
Patients receive brentuximab vedotin IV over 30 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Outcomes
Primary Outcome Measures
Disease control rate (DCR) defined as proportion of patients who had complete response, partial response or stable disease by Response Evaluation Criteria in Solid Tumors version 4.1
A DCR of 50% or higher is considered as clinically significant. If the trial is not stopped early and all 50 patients are accrued, point estimate along with 95% credible interval will be provided. Logistic regression model will be utilized to assess the effect of patient prognostic factors on the response status if sufficient number of patients with stable disease or better response to the treatment are observed.
Secondary Outcome Measures
Tumor characteristics
Patients' demographic and tumor characteristics will be analyzed, with categorical variables summarized in frequency tables while continuous variables summarized using mean (plus or minus standard deviation) and median (range). The student t-test/Wilcoxon test and analysis of variance (ANOVA)/Kruskal-Wallis test will be used to compare continuous variables between different patient groups. The chi-square test or the Fisher's exact test will be applied to assess the association between two categorical variables.
Time to progression
The distribution of time-to-event endpoints will be estimated using the method of Kaplan and Meier. Comparison of time-to-event endpoints by important patient characteristics will be made using the log-rank test. Cox proportional hazard regression will be employed for multi-covariate analysis on time-to-event outcomes when appropriate.
Overall survival
The distribution of time-to-event endpoints will be estimated using the method of Kaplan and Meier. Comparison of time-to-event endpoints by important patient characteristics will be made using the log-rank test. Cox proportional hazard regression will be employed for multi-covariate analysis on time-to-event outcomes when appropriate.
CD30+ expression levels
The student t-test/Wilcoxon test and ANOVA/Kruskal-Wallis test will be used to compare CD30+ expression levels by response status.
Full Information
NCT ID
NCT03007030
First Posted
December 28, 2016
Last Updated
August 30, 2023
Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT03007030
Brief Title
Brentuximab Vedotin in Treating Patients With CD30+ Malignant Mesothelioma That Cannot Be Removed by Surgery
Official Title
Phase II Trial of Adcetris (Brentuximab Vedotin) in CD30+ Malignant Mesothelioma
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 5, 2017 (Actual)
Primary Completion Date
April 30, 2024 (Anticipated)
Study Completion Date
April 30, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This phase II trial studies how well brentuximab vedotin works in treating patients with CD30 positive (+) malignant mesothelioma that cannot be removed by surgery. Monoclonal antibodies, such as brentuximab vedotin, may interfere with the ability of tumor cells to grow and spread.
Detailed Description
PRIMARY OBJECTIVES:
I. To assess 4-month disease control rate (DCR) in pre-treated patients with unresectable malignant pleural mesothelioma (MPM) treated with brentuximab vedotin.
SECONDARY OBJECTIVES:
I. To evaluate the response rate, progression-free and overall survival, and safety/toxicity of brentuximab vedotin in CD30+ malignant mesothelioma.
II. To prospectively evaluate the incidence of CD30+ expression in malignant mesothelioma during the screening process.
III. To determine whether CD30+ expression levels in tumor tissue correlate to response to brentuximab vedotin.
EXPLORATORY OBJECTIVES:
I. To collect archival or new tissue and blood for correlative studies. II. Next generation sequencing (NGS) will be conducted on adequate tumor tissue specimens.
III. Exploratory analysis: Bank peripheral blood at baseline for subsequent cytokine or reverse phase protein array (RPPA).
OUTLINE:
Patients receive brentuximab vedotin intravenously (IV) over 30 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days, 3 months, 6 months and then every 6 months thereafter.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
CD30-Positive Neoplastic Cells Present, Malignant Mesothelioma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
55 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Treatment (brentuximab vedotin)
Arm Type
Experimental
Arm Description
Patients receive brentuximab vedotin IV over 30 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
Brentuximab Vedotin
Other Intervention Name(s)
ADC SGN-35, Adcetris, Anti-CD30 Antibody-Drug Conjugate SGN-35, Anti-CD30 Monoclonal Antibody-MMAE SGN-35, Anti-CD30 Monoclonal Antibody-Monomethylauristatin E SGN-35, cAC10-vcMMAE, SGN-35
Intervention Description
Given IV
Intervention Type
Other
Intervention Name(s)
Laboratory Biomarker Analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Disease control rate (DCR) defined as proportion of patients who had complete response, partial response or stable disease by Response Evaluation Criteria in Solid Tumors version 4.1
Description
A DCR of 50% or higher is considered as clinically significant. If the trial is not stopped early and all 50 patients are accrued, point estimate along with 95% credible interval will be provided. Logistic regression model will be utilized to assess the effect of patient prognostic factors on the response status if sufficient number of patients with stable disease or better response to the treatment are observed.
Time Frame
At 4 months
Secondary Outcome Measure Information:
Title
Tumor characteristics
Description
Patients' demographic and tumor characteristics will be analyzed, with categorical variables summarized in frequency tables while continuous variables summarized using mean (plus or minus standard deviation) and median (range). The student t-test/Wilcoxon test and analysis of variance (ANOVA)/Kruskal-Wallis test will be used to compare continuous variables between different patient groups. The chi-square test or the Fisher's exact test will be applied to assess the association between two categorical variables.
Time Frame
Up to 5 years
Title
Time to progression
Description
The distribution of time-to-event endpoints will be estimated using the method of Kaplan and Meier. Comparison of time-to-event endpoints by important patient characteristics will be made using the log-rank test. Cox proportional hazard regression will be employed for multi-covariate analysis on time-to-event outcomes when appropriate.
Time Frame
Up to 5 years
Title
Overall survival
Description
The distribution of time-to-event endpoints will be estimated using the method of Kaplan and Meier. Comparison of time-to-event endpoints by important patient characteristics will be made using the log-rank test. Cox proportional hazard regression will be employed for multi-covariate analysis on time-to-event outcomes when appropriate.
Time Frame
Up to 5 years
Title
CD30+ expression levels
Description
The student t-test/Wilcoxon test and ANOVA/Kruskal-Wallis test will be used to compare CD30+ expression levels by response status.
Time Frame
Up to 5 years
Other Pre-specified Outcome Measures:
Title
Cytokines in peripheral blood
Description
Appropriate statistical approaches will be applied to the exploratory analysis of the cytokines.
Time Frame
At time of disease progression, assessed up to 5 years
Title
Reverse phase protein array (RPPA) in peripheral blood
Description
Appropriate statistical approaches will be applied to the exploratory analysis of RPPA.
Time Frame
At time of disease progression, assessed up to 5 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care
Female subject is either: a. post-menopausal for at least one year before the screening visit; or b. surgically sterilized; or c. willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study and at least 6 months after the last dose of brentuximab vedotin
Male subject, even if surgically sterilized (i.e., status postvasectomy), agrees to use an acceptable barrier method for contraception (condom with a spermicidal agent), or completely abstain from heterosexual intercourse during the entire study treatment period through 6 months after the last dose of brentuximab vedotin
Absolute neutrophil count (ANC) > 1500/mm^3
Platelets > 100,000/mm^3
Hemoglobin (Hgb) > 8.5 g/dL
Total bilirubin =< 1.5 x upper limit of normal (ULN)
Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 3 x ULN; AST and/or ALT may be up to 5 X ULN if with known liver metastases (mets)
Calculated creatinine clearance must be >= 30 mL/minute
Eastern Cooperative Oncology Group (ECOG) performance status 0-2
Pathologic diagnosis of malignant mesothelioma (any primary site is acceptable, any histology is acceptable)
Have unresectable malignant mesothelioma (any histology)
Positive CD30+ immunohistochemical expression
Any line of prior therapy - patients may be chemo-naive or chemo-refractory (any line)
Patients must have measurable disease by modified Response Evaluation Criteria in Solid Tumors (RECIST) or RECIST; examinations for assessment of measurable disease must have been completed within 28 days prior to registration
Exclusion Criteria:
Radiation therapy to more than 25% of the bone marrow; whole pelvic radiation is considered to be over 25%
Prior allogeneic bone marrow or organ transplantation
Female subject who is pregnant or breast-feeding; confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (B-hCG) pregnancy test result obtained during screening; pregnancy testing is not required for post-menopausal or surgically sterilized women
Patient has received other investigational drugs with 14 days before enrollment
Serious medical or psychiatric illness likely to interfere with participation in this clinical study
No prior history of malignancy within 2 years, unless cured of a skin cancer or a stage I-III solid tumor; no prior hematologic malignancy within 3 years
Known hypersensitivity to brentuximab vedotin components
Persons who are incarcerated at time of enrollment (e.g., prisoners) or likely to become incarcerated during the study
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Anne S. Tsao
Phone
713-792-6363
Email
astsao@mdanderson.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anne S Tsao
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anne S. Tsao
Phone
713-792-6363
First Name & Middle Initial & Last Name & Degree
Anne S. Tsao
12. IPD Sharing Statement
Links:
URL
http://www.mdanderson.org
Description
M D Anderson Cancer Center
Learn more about this trial
Brentuximab Vedotin in Treating Patients With CD30+ Malignant Mesothelioma That Cannot Be Removed by Surgery
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