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Brentuximab Vedotin in Treating Patients With CD30+ Malignant Mesothelioma That Cannot Be Removed by Surgery

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ClinicalTrials.gov Identifier: NCT03007030
Recruitment Status : Recruiting
First Posted : December 30, 2016
Last Update Posted : December 4, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Tracking Information
First Submitted Date  ICMJE December 28, 2016
First Posted Date  ICMJE December 30, 2016
Last Update Posted Date December 4, 2019
Actual Study Start Date  ICMJE April 5, 2017
Estimated Primary Completion Date April 30, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 16, 2019)
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 [ Time Frame: At 4 months ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: December 28, 2016)
Disease Control Rate (DCR) in Pre-Treated Participants with Unresectable Malignant Pleural Mesothelioma (MPM) Treated with Brentuximab Vedotin [ Time Frame: 4 months ]
Disease control rate (DCR) defined as proportion of patients who had complete response, partial response or stable disease by RESIST 4.1.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 16, 2019)
  • Tumor characteristics [ Time Frame: Up to 5 years ]
    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 [ Time Frame: Up to 5 years ]
    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 [ Time Frame: Up to 5 years ]
    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 [ Time Frame: Up to 5 years ]
    The student t-test/Wilcoxon test and ANOVA/Kruskal-Wallis test will be used to compare CD30+ expression levels by response status.
Original Secondary Outcome Measures  ICMJE
 (submitted: December 28, 2016)
Time to Progression in Pre-Treated Participants with Unresectable Malignant Pleural Mesothelioma (MPM) Treated with Brentuximab Vedotin [ Time Frame: 6 weeks ]
Time to progression assessed by RESIST 4.1. Time to progression estimated using the method of Kaplan and Meier.
Current Other Pre-specified Outcome Measures
 (submitted: May 16, 2019)
  • Cytokines in peripheral blood [ Time Frame: At time of disease progression, assessed up to 5 years ]
    Appropriate statistical approaches will be applied to the exploratory analysis of the cytokines.
  • Reverse phase protein array (RPPA) in peripheral blood [ Time Frame: At time of disease progression, assessed up to 5 years ]
    Appropriate statistical approaches will be applied to the exploratory analysis of RPPA.
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Brentuximab Vedotin in Treating Patients With CD30+ Malignant Mesothelioma That Cannot Be Removed by Surgery
Official Title  ICMJE Phase II Trial of Adcetris (Brentuximab Vedotin) in CD30+ Malignant Mesothelioma
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • CD30-Positive Neoplastic Cells Present
  • Malignant Mesothelioma
Intervention  ICMJE
  • Drug: Brentuximab Vedotin
    Given IV
    Other Names:
    • 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
  • Other: Laboratory Biomarker Analysis
    Correlative studies
Study Arms  ICMJE Experimental: Treatment (brentuximab vedotin)
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.
Interventions:
  • Drug: Brentuximab Vedotin
  • Other: Laboratory Biomarker Analysis
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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 16, 2019)
55
Original Estimated Enrollment  ICMJE
 (submitted: December 28, 2016)
50
Estimated Study Completion Date  ICMJE April 30, 2022
Estimated Primary Completion Date April 30, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Anne S. Tsao 713-792-6363 astsao@mdanderson.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03007030
Other Study ID Numbers  ICMJE 2016-0514
NCI-2017-00069 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2016-0514 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee No
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  ICMJE Not Provided
Responsible Party M.D. Anderson Cancer Center
Study Sponsor  ICMJE M.D. Anderson Cancer Center
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Anne S Tsao M.D. Anderson Cancer Center
PRS Account M.D. Anderson Cancer Center
Verification Date December 2019

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