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Trial record 22 of 185 for:    DCLRE1C

Study of the Safety and Efficacy of Amatuximab in Combination With Pemetrexed and Cisplatin in Subjects With Unresectable Malignant Pleural Mesothelioma (MPM) (ARTEMIS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02357147
Recruitment Status : Terminated (Due to business reasons)
First Posted : February 6, 2015
Last Update Posted : June 24, 2019
Sponsor:
Information provided by (Responsible Party):
Morphotek

Tracking Information
First Submitted Date  ICMJE January 14, 2015
First Posted Date  ICMJE February 6, 2015
Last Update Posted Date June 24, 2019
Actual Study Start Date  ICMJE November 3, 2015
Actual Primary Completion Date November 30, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 20, 2019)
Safety and tolerability as a measure of number of participants with Adverse Events (AEs)/Serious Adverse Events (SAEs) [ Time Frame: Until date of death or up to 60 months ]
Safety assessments will consist of monitoring and recording all adverse events, including adverse events of interest, hypersensitivity adverse events and serious adverse events; regular monitoring of hematology and blood chemistry.
Original Primary Outcome Measures  ICMJE
 (submitted: February 2, 2015)
Overall Survival (OS) [ Time Frame: Until date of death or up to 60 months ]
OS is defined as the time from the date of randomization to the date of death, regardless of cause.
Change History Complete list of historical versions of study NCT02357147 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: February 2, 2015)
  • Progression Free Survival (PFS) [ Time Frame: First observation of disease progression or until date of death or up to 60 months ]
    PFS is defined as the time (in weeks) from the date of randomization to the date of the first observation of progression as determined by the independent radiologic assessment using the modified Response Evaluation Criteria In Solid Tumors (RECIST) criteria or the date of death, whichever comes first, regardless of the cause.
  • Objective Response Rate [ORR] [ Time Frame: Until date of death or up to 60 months ]
    ORR (the proportion of subjects with complete response [CR] and partial response [PR]) as defined by the modified RECIST criteria using an independent radiologic review of computed tomography (CT)/Magnetic resonance imaging (MRI) scan. Objective response will be assessed at select visits during the Combination Treatment Phase as well as the Maintenance Treatment Phase.
  • Duration of response (DR) [ Time Frame: First documentation of objective tumor progression or until date of death or up to 60 months ]
    DR is defined as the time from the first documentation of objective tumor response to the first documentation of objective tumor progression or to death on study (ie, within 30 days after the last dose of Test Article).
  • Disease control rates (DCR) [ Time Frame: Until date of death or up to 60 months ]
    DCR is the proportion of subjects with CR, PR, or stable disease (SD) as defined by the modified RECIST criteria using an independent radiologic review of CT/MRI scan.
  • Duration of disease control (DDC) [ Time Frame: First documentation of objective tumor progression or until date of death or up to 60 months ]
    DDC is defined as the time from the first documentation of objective tumor response or SD to the first documentation of objective tumor progression or to death.
  • Health related quality of life (QOL) [ Time Frame: Until date of death or up to 60 months ]
    QOL as measured by the Lung Cancer Symptom Scale for mesothelioma (LCSS-Meso; Hollen, et al., 2006) as the treatment population average across the duration of the trial for 9 items.
  • Duration of Performance Status Maintenance (DPSM) [ Time Frame: Until date of death or up to 60 months ]
    DPSM is defined as the time from randomization until the last time the performance status was no worse than at baseline or to death on study.
  • Safety and tolerability as a measure of number of participants with Adverse Events (AEs)/Serious Adverse Events (SAEs) [ Time Frame: Until date of death or up to 60 months ]
    Safety assessments will consist of monitoring and recording all adverse events, including adverse events of interest, hypersensitivity adverse events and serious adverse events; regular monitoring of hematology, blood chemistry, and urine values; regular monitoring of electrocardiograms (ECGs); periodic measurement of vital signs; and performance of physical examinations.
  • Pharmacokinetic (PK) and pharmacodynamic (PD) profile [ Time Frame: Serum samples of amatuximab at Day 1 of every Cycle during the combination treatment phase and every third cycle during the maintenance treatment phase until first evidence of disease progression or up to 60 ]
    PK and PD profile is analyzed to study exposure-response relationships for effects of amatuximab on OS, PFS, ORR, DR, DCR, DDC and DPSM and hypersensitivity adverse events.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of the Safety and Efficacy of Amatuximab in Combination With Pemetrexed and Cisplatin in Subjects With Unresectable Malignant Pleural Mesothelioma (MPM)
Official Title  ICMJE A Randomized, Double-blind, Placebo-controlled Study of the Safety and Efficacy of Amatuximab in Combination With Pemetrexed and Cisplatin in Subjects With Unresectable Malignant Pleural Mesothelioma
Brief Summary

This study was originally designed as a multicenter, double-blind, randomized, parallel-group study, using a placebo control or amatuximab 5 milligrams per kilogram (mg/kg), administered weekly, designed to evaluate the safety and efficacy of amatuximab in combination with pemetrexed and cisplatin in participants with unresectable Malignant Pleural Mesothelioma (MPM) who have not received prior systemic therapy.

Per a business decision made by the Sponsor, participants who were randomized to amatuximab and are still on active treatment at the time of the protocol amendment may consent to continue to receive weekly treatment with amatuximab until disease progression or intolerable toxicity at the discretion of the principal investigator. Participants randomized to placebo or who were in follow-up at the time of the amendment have been discontinued from the study.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
Condition  ICMJE Mesothelioma, Malignant
Intervention  ICMJE
  • Drug: Placebo

    Combination Phase - Placebo will be administered IV (intravenous infusion) once weekly for six 21-day cycles.

    Maintenance Phase - Placebo will be administered IV (intravenous infusion) once weekly until disease progression.

  • Drug: Amatuximab

    Combination Phase - Amatuximab 5mg/kg will be administered IV (intravenous infusion) once weekly for six 21-day cycles.

    Maintenance Phase - Amatuximab 5mg/kg will be administered IV (intravenous infusion) once weekly until disease progression.

  • Drug: Pemetrexed
    Combination Phase - Pemetrexed 500 mg/m2 will be administered IV on Day 1 of each 21-day cycle for 6 cycles.
  • Drug: Cisplatin
    Combination Phase - Cisplatin 75 mg/m2 will be administered IV on Day 1 of each 21-day cycle for 6 cycles.
Study Arms  ICMJE
  • Experimental: Arm 1

    Combination Phase - Amatuximab + Pemetrexed and Cisplatin

    Maintenance Phase - Amatuximab

    Interventions:
    • Drug: Amatuximab
    • Drug: Pemetrexed
    • Drug: Cisplatin
  • Experimental: Arm 2

    Combination Phase - Placebo + Pemetrexed and Cisplatin

    Maintenance Phase - Placebo

    Interventions:
    • Drug: Placebo
    • Drug: Pemetrexed
    • Drug: Cisplatin
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 Terminated
Actual Enrollment  ICMJE
 (submitted: February 2, 2017)
108
Original Estimated Enrollment  ICMJE
 (submitted: February 2, 2015)
610
Actual Study Completion Date  ICMJE November 30, 2018
Actual Primary Completion Date November 30, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Are at least 18 years of age at the time of informed consent
  2. Have confirmed diagnosis of MPM with the following characteristics:

    • Unresectable disease (defined as the participant not being a candidate for curative surgery)
    • Epithelial type
    • Have an archived tissue sample to be submitted either as a formalin fixed paraffin-embedded (FFPE) tumor block, or 5 to 15 unstained slides
  3. Have measurable disease at Screening by computed tomography (CT) (or magnetic resonance imaging [MRI]) as defined by at least 1 lesion of greater than or equal to 1.5 cm in the longest diameter for a non-lymph node or greater than or equal to 1.5 cm in the short-axis diameter for a lymph node that is serially measurable according to the modified RECIST criteria
  4. Have other significant medical conditions well-controlled and stable in the opinion of the investigator for at least 30 days prior to Day 1
  5. Have an Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1 at Screening
  6. Have a life expectancy of at least 3 months, as estimated by the investigator
  7. Have adequate organ reserve as determined by laboratory test results obtained within 2 weeks prior to Study Day 1 as indicated below:

    • Absolute neutrophil count greater than or equal to 1.5 x 109/L
    • Platelet count greater than or equal to 100 x 109/L
    • Hemoglobin greater than or equal to 9 g/dL
    • Serum bilirubin less than or equal to 1.5 x upper limit of normal (ULN) (Participants with serum bilirubin abnormalities greater than this specified limit are eligible only if they have known Gilberts disease)
    • Aspartate aminotransferase less than or equal to 3 x ULN
    • Alanine aminotransferase less than or equal to 3 x ULN
    • Alkaline phosphatase less than or equal to 3 x ULN
  8. Have a calculated serum creatinine clearance greater than or equal to 45 mL/min using the Cockcroft-Gault equation
  9. Participants of childbearing potential must be surgically sterile or consent to use a highly effective method of contraception throughout the study period. All females will be considered to be of childbearing potential unless they are postmenopausal (amenorrheic for at least 12 consecutive months, in the appropriate age group, and without other known or suspected cause) or have been sterilized surgically (ie, bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing). If a participant of childbearing potential is neither surgically sterile nor postmenopausal, highly effective contraceptive measures must start either prior to or at Screening and continue throughout the entire study period and for at least 6 months after the last dose of chemotherapy and at least 30 days after the last dose of Test Article (amatuximab or placebo) is administered (whichever is later). A highly effective method of contraception is defined as one that results in a low failure rate (ie, less than 1% per year) when used consistently and correctly. Periodic abstinence, the rhythm method, the withdrawal method, condoms, and diaphragms are not acceptable methods of contraception. Women of childbearing potential must also refrain from egg cell donation for 6 months after the final dose of investigational product
  10. Male participants must have had a successful vasectomy (confirmed azoospermia) or they and their female partners must meet the criteria above (ie, not of childbearing potential or practicing highly effective contraception throughout the study period and for 6 months after discontinuation of chemotherapy and for 5 weeks after Test Article (amatuximab or placebo) discontinuation (whichever is later). No sperm donation is allowed during the study period and for 90 days after Test Article discontinuation
  11. Be willing and able to provide written informed consent
  12. Be willing and able to comply with all aspects of the protocol
  13. Participants who were enrolled in the study and randomized to the amatuximab treatment arm may, at the discretion of the principle investigator (PI), consent to continue to receive amatuximab therapy until disease progression, intolerable toxicity, or withdraw of consent

Exclusion Criteria:

  1. Have any history of the following:

    • Prior systemic therapy or radiotherapy for MPM; local radiotherapy of noncurative intent (ie, for prevention of instrument-tract recurrence and/or symptom control) is permitted
    • Evidence of other active, invasive malignancy requiring treatment within the past 5 years; noninvasive cancer history (such as carcinoma-in-situ [CIS] that has been resected) is allowed
  2. Currently have mesothelioma of the sarcomatous type, mixed histologic disease, or have malignant peritoneal mesothelioma
  3. Have confirmed presence of central nervous system metastases
  4. Active viral hepatitis or active human immunodeficiency virus infection
  5. Have evidence of any other serious systemic disease, including active bacterial or fungal infection, or any medical condition that, in the opinion of the investigator(s) could affect the participant's safety or interfere with the study assessments
  6. Clinically significant heart disease (eg, congestive heart failure of New York Heart Association Class 3 or 4, angina not well controlled by medication, or myocardial infarction within 6 months)
  7. Electrocardiogram (ECG) demonstrating clinically significant arrhythmias (Note: participants with chronic atrial arrhythmia, ie, atrial fibrillation or paroxysmal supraventricular tachycardia, are eligible). A clinically significant ECG abnormality, including a marked prolonged QT/QTc interval (eg, a repeated demonstration of a QTc interval of greater than 500 ms)
  8. Have known intolerance to the Test Article (ie, documented hypersensitivity AE to prior monoclonal antibody therapy, or to amatuximab or any of its excipients)
  9. Pregnant and/or lactating females are excluded; a negative beta-human chorionic gonadotropin [B-hCG]) is required during Screening, and a separate local assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of Test Article
  10. Have any medical or other condition that in the opinion of the investigator(s) would preclude the participant's participation in a clinical study
  11. Are scheduled for debulking surgery during the study
  12. Are currently enrolled in another clinical study or used any investigational drug or device within 30 days (or 5 x the half-life of the investigational drug/device, whichever is longer) preceding informed consent
  13. Participants previously randomized to placebo
  14. Participants who have radiographic or clinical disease progression or intolerable toxicity such that ongoing amatuximab treatment through this study is not appropriate
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 99 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   France,   Germany,   Italy,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02357147
Other Study ID Numbers  ICMJE MORAb-009-201
2014-004489-85 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Morphotek
Study Sponsor  ICMJE Morphotek
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Morphotek
Verification Date February 2017

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