Back to resultsA Study of Carboplatin and Paclitaxel With or Without MEDI-575 in Untreated, Advanced Non-Small Cell Lung Cancer
Primary Purpose
Non-small Cell Lung Cancer
Status
Terminated
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Carboplatin
Paclitaxel
MEDI-575
Sponsored by
About this trial
This is an interventional treatment trial for Non-small Cell Lung Cancer focused on measuring Non-small cell lung cancer, NSCLC, MEDI-575, Platelet-derived growth factor receptor alpha
Eligibility Criteria
Inclusion Criteria:
- Histologically confirmed inoperable Stage IIIB or Stage IV non-small cell lung cancer according to the Seventh Edition of the American Joint Committee on Cancer (AJCC) Tumor Node Metastases (TNM) staging system (only participants with squamous cell carcinoma will be enrolled)
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Life expectancy of greater than or equal to (>=) 3 months
- Prothrombin time elevation less than or equal to (<=) Grade 2 by National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) criteria (Version 4.0) is acceptable for participants on anticoagulant therapy
- Adequate hematologic function
- Adequate organ function
- Suitable candidates for therapy with carboplatin/paclitaxel
- Participants must have at least 1 lesion that is measurable using Response Evaluation Criteria for Solid Tumors
- Participants must be willing to consent to allow collection of archived NSCLC tumor samples
- Negative serum beta-human chorionic gonadotropin (beta-hCG) test (women of childbearing potential only)
- Females of childbearing potential, unless surgically sterile has a sterile male partner, is premenarchal or at least 2 years postmenopausal, or practices abstinence, must use 2 effective methods of avoiding pregnancy (including oral, transdermal, or implanted contraceptives, intrauterine device, female condom with spermicide, diaphragm with spermicide, cervical cap, or use of a condom with spermicide by the sexual partner) from screening, and must agree to continue using such precautions for 90 days after the final dose of treatment; cessation of birth control after this point should be discussed with a responsible physician
- Males, unless surgically sterile, must use 2 effective methods of birth control with a female partner and must agree to continue using such contraceptive precautions from screening through 90 days after the final dose of treatment
Exclusion Criteria:
- At discretion of the investigator regarding safety of the participants
- Concurrent enrollment in another clinical study
- Any concurrent chemotherapy, radiotherapy, immunotherapy, biologic, or hormonal therapy for treatment of cancer
- Previous monoclonal antibody (mAb) treatment specifically directed against platelet-derived growth factor (PDGF) or PDGF receptors
- History of serious allergy or reaction to any component of the MEDI-575 formulation
- Receipt of any previous systemic anticancer therapies for advanced or metastatic disease
- Previous adjuvant/neoadjuvant radiotherapy or chemotherapy for treatment of previous nonmetastatic disease is allowed provided that 6 months have elapsed from the end of such therapies to the time of enrollment
- New York Heart Association >= Class II congestive heart failure
- History of myocardial infarction, unstable angina, transient ischemic attack or stroke within the previous 6 months prior to enrollment
- History of other invasive malignancy within 5 years except for cervical carcinoma in situ (CIS), non-melanomatous carcinoma of the skin or ductal carcinoma in situ (DCIS) of the breast that have been surgically cured
- Evidence of active infection requiring the use of systemic antimicrobial treatment within 72 hours prior to initial treatment with MEDI-575
- Use of immunosuppressive medication (inhaled and topical corticosteroids are permitted) within 7 days prior to enrollment
- Systemic immunosuppressive steroid therapy
- Participants may take replacement doses of steroids if on a stable dose for at least 2 weeks prior to enrollment
- History of active human immunodeficiency virus (HIV) or active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
- Pregnancy or lactation
- Previous medical history or evidence of an inter-current illness
- Any physical, social, or psychiatric condition which would prevent effective cooperation or participation in the study
Sites / Locations
- Research Site
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Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
Carboplatin/Paclitaxel
Carboplatin/Paclitaxel + MEDI-575
Arm Description
Carboplatin/paclitaxel regimen (carboplatin area under the plasma concentration-time curve [AUC] of 6 milligram per milliliter into minute [mg/mL*min], and paclitaxel 200 milligram per square meter [mg/m^2]) administered as an intravenous (IV) infusion once every 21 days on Day 1, for a total of 6 doses (cycles) until unacceptable toxicity, disease progression, or other reasons for participant withdrawal. Subjects were enrolled from North America/European Union (EU) and Japan regions.
Carboplatin/paclitaxel regimen (carboplatin AUC = 6 mg/mL*min, and paclitaxel 200 mg/m^2) followed by MEDI-575 at a dose of 25 milligram per kilogram (mg/kg) administered as an IV infusion once every 21 days on Day 1 for a total of 6 cycles until unacceptable toxicity, disease progression, initiation of alternative anticancer therapy, or other reasons for participant withdrawal. MEDI-575 alone continued in those participants who achieved stable disease or better at the completion of carboplatin/paclitaxel therapy and did not demonstrate toxicity to MEDI-575. Subjects were enrolled from North America/European Union (EU) and Japan regions.
Outcomes
Primary Outcome Measures
Number of Participants With Dose Limiting Toxicities (DLT): Phase 1b
A DLT was defined as:
Any treatment-related Grade 3 or higher non-hematologic toxicity that occurred during the DLT assessment period with the following exceptions:
Grade 3 fever (in the absence of neutropenia) defined as more than (>) 40.0 degree Celcius (> 104.0 degree Fahrenheit) that resolved to normal or baseline within 24 hours of treatment and was not considered a serious adverse event (SAE); or
Grade 3 rigors/chills that responded to optimal therapy.
Any treatment-related Grade 3 or higher hematologic toxicity.
Progression Free-Survival (PFS)
Progression-free survival defined as the time from randomization (randomization referred to the date of treatment assignment) to disease progression (defined according to Response Evaluation Criteria for Solid Tumors [RECIST] version 1.1 guidelines) or death due to any cause, whichever occurs first. Participants without progression or death at the time of analysis were censored at their last date of tumor evaluation. PFS was assessed only in North America/European Union (EU) participants. Progression-free survival was evaluated using Kaplan-Meier method.
Secondary Outcome Measures
Best Overall Response
Best overall response of a participant was defined as the best tumor response [Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD)] observed during the trial period assessed according to the Response Evaluation Criteria for Solid Tumors (RECIST) version 1.1 criteria. The participant's best overall response assignment depended on the findings of both target and non-target disease and also on the appearance of new lesions. CR was defined as disappearance of tumor lesions, PR was defined as a decrease of at least 30 percent (%) in the sum of diameters of target lesion, SD was defined as steady state of disease, and PD was defined as an increase of at least 20% in the sum of diameters of target lesions.
Objective Response Rate (ORR)
The ORR defined as the percentage of participants with confirmed CR or confirmed PR according to RECIST version 1.1 guidelines. Confirmed responses were those that persist on repeat imaging or assessment greater than or equal to (>=) 4 weeks after the initial documentation of response. The ORR was evaluated using Kaplan-Meier method.
Time to Response (TTR)
The TTR was measured from initiation of study treatment to the first documentation of objective response (OR). The OR defined as the participants with confirmed CR or confirmed PR according to RECIST version 1.1 guidelines. Confirmed responses were those that persist on repeat imaging or assessment >=4 weeks after the initial documentation of response. The TTR was evaluated using Kaplan-Meier method.
Duration of Response (DR)
The DR defined as the duration from the first documentation of OR to the first documented disease progression. Participants without progression at the time of analysis were censored at their last date of tumor evaluation. The DR was evaluated using Kaplan-Meier method.
Time to Progression (TTP)
The TTP was measured from randomization until the documentation of disease progression. Disease progression defined according to RECIST version 1.1 guidelines. Participants without progression at the time of analysis were censored at their last date of tumor evaluation. The TTP was evaluated using Kaplan-Meier method.
Overall Survival (OS)
Overall survival defined as the time from initiation of study treatment until death due to any cause. Participants who were still alive at the time of analysis were censored at their last date of last contact. The OS was evaluated using Kaplan-Meier method.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs
Laboratory investigations included hematology, coagulation, serum chemistry and urinalysis parameters. Participants with abnormalities in these laboratory investigations recorded as AEs or SAEs were reported.
Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as AEs
The 12-lead ECG data were performed and obtained in triplicate that is 3 ECGs obtained within a 5 minute time period. Number of participants with ECG abnormalities were reported and recorded as AEs.
Maximum Observed Serum Concentration (Cmax) of MEDI-575 After First Dose
The Cmax of MEDI-575 after first dose is reported.
Time of Maximal Observed Concentration (Tmax) of MEDI-575 After First Dose
The tmax refers to the time after dosing when a drug attains its highest measurable concentration (Cmax). The Tmax of MEDI-575 after first dose is reported.
Area Under the Concentration-Time Curve Over the Dosing Interval (AUCtau) of MEDI-575 After First Dose
The AUCtau defined as area under the plasma concentration time profile from time zero to the end of the dosing interval (tau). The AUCtau of MEDI-575 after first dose is reported.
Maximum Serum Concentration at Steady State (Cmax,ss) of MEDI-575
The Cmax,ss of MEDI-575 is reported.
Time to Maximum Serum Concentration at Steady State (Tmax,ss) of MEDI-575
The Tmax,ss of MEDI-575 is reported.
Trough Serum Concentration at Steady State (Ctrough,ss) of MEDI-575
The Ctrough,ss of MEDI-575 is reported.
Percentage of Participants With Positive Anti-MEDI-575 Antibodies
Immunogenicity assessment included determination of anti-drug (MEDI-575) antibodies in serum samples.
Number of Participants With Platelet-derived Growth Factor Receptor Alpha (PDGFRα) Expression in Tumor Cells of Archived Tumor Samples
The immunohistochemical expression of PDGFRα in tumor cells in archived formalin-fixed paraffin-embedded tissue samples collected at baseline are reported. The transmembrane receptor tyrosine kinase PDGFRα plays an important role in human carcinogenesis, both as a direct target on tumor cells and also as a mediator of stromal support for cancer cell growth. The data of positive-staining tumor cells are reported in 3 categories: intensity (1+ [weak expression, staining in <5 % of tumor cells]; 2+ [moderate expression, staining in >= 5 % of tumor cells]; and 3+ [strong expression, staining in >5 % of the tumor cells]), localization (membranous, cytoplasmic, or nuclear), and frequency (rare, occasional, or frequent).
Number of Participants With PDGFRα Expression in Stromal Cells of Archived Tumor Samples
The immunohistochemical expression of PDGFRα in stromal cells in archived formalin-fixed paraffin-embedded tissue samples collected at baseline are reported. The transmembrane receptor tyrosine kinase PDGFRα plays an important role in human carcinogenesis, both as a direct target on tumor cells and also as a mediator of stromal support for cancer cell growth. The data of positive-staining stromal cells are reported in 3 categories: intensity (1+ [weak expression, staining in <5 % of tumor cells]; 2+ [moderate expression, staining in >= 5 % of tumor cells]; and 3+ [strong expression, staining in >5 % of the tumor cells]), localization (membranous, cytoplasmic, or nuclear), and frequency (rare, occasional, or frequent).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01268059
Brief Title
A Study of Carboplatin and Paclitaxel With or Without MEDI-575 in Untreated, Advanced Non-Small Cell Lung Cancer
Official Title
A Phase 1b/2 Randomized Study of MEDI-575 in Combination With Carboplatin Plus Paclitaxel Versus Carboplatin Plus Paclitaxel Alone in Adult Subjects With Previously Untreated, Advanced Non-Small Cell Lung Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
November 2020
Overall Recruitment Status
Terminated
Why Stopped
In conjunction with the overall risk-benefit assessment, study was terminated prematurely due to safety concerns.
Study Start Date
December 16, 2010 (Actual)
Primary Completion Date
September 11, 2013 (Actual)
Study Completion Date
September 11, 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
MedImmune LLC
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to evaluate the dose, antitumor activity, safety and pharmacology of MEDI-575 in combination with carboplatin/paclitaxel in subjects with previously untreated, advanced non-small cell lung cancer (NSCLC).
Detailed Description
This is a Phase 1b/2, multicenter, open-label study of MEDI-575 to evaluate the dose, anti-tumor activity, safety, and pharmacology (pharmacokinetics, immunogenicity, and biomarkers) of MEDI-575 in combination with carboplatin/paclitaxel in subjects with previously untreated, advanced non-small cell lung cancer. This study has two phases: dose determination (Phase 1b) and randomization (Phase 2).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-small Cell Lung Cancer
Keywords
Non-small cell lung cancer, NSCLC, MEDI-575, Platelet-derived growth factor receptor alpha
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
99 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Carboplatin/Paclitaxel
Arm Type
Active Comparator
Arm Description
Carboplatin/paclitaxel regimen (carboplatin area under the plasma concentration-time curve [AUC] of 6 milligram per milliliter into minute [mg/mL*min], and paclitaxel 200 milligram per square meter [mg/m^2]) administered as an intravenous (IV) infusion once every 21 days on Day 1, for a total of 6 doses (cycles) until unacceptable toxicity, disease progression, or other reasons for participant withdrawal. Subjects were enrolled from North America/European Union (EU) and Japan regions.
Arm Title
Carboplatin/Paclitaxel + MEDI-575
Arm Type
Experimental
Arm Description
Carboplatin/paclitaxel regimen (carboplatin AUC = 6 mg/mL*min, and paclitaxel 200 mg/m^2) followed by MEDI-575 at a dose of 25 milligram per kilogram (mg/kg) administered as an IV infusion once every 21 days on Day 1 for a total of 6 cycles until unacceptable toxicity, disease progression, initiation of alternative anticancer therapy, or other reasons for participant withdrawal. MEDI-575 alone continued in those participants who achieved stable disease or better at the completion of carboplatin/paclitaxel therapy and did not demonstrate toxicity to MEDI-575. Subjects were enrolled from North America/European Union (EU) and Japan regions.
Intervention Type
Drug
Intervention Name(s)
Carboplatin
Intervention Description
Carboplatin (carboplatin area under the plasma concentration-time curve [AUC] of 6 milligram per milliliter into minute [mg/mL*min] administered as an intravenous (IV) infusion once every 21 days on Day 1, for a total of 6 doses (cycles) until unacceptable toxicity, disease progression, or other reasons for participant withdrawal.
Intervention Type
Drug
Intervention Name(s)
Paclitaxel
Intervention Description
Paclitaxel 200 milligram per square meter (mg/m^2) administered as an intravenous (IV) infusion once every 21 days on Day 1, for a total of 6 doses (cycles) until unacceptable toxicity, disease progression, or other reasons for participant withdrawal.
Intervention Type
Drug
Intervention Name(s)
MEDI-575
Intervention Description
MEDI-575 at a dose of 25 milligram per kilogram (mg/kg) administered as an IV infusion once every 21 days on Day 1 for a total of 6 cycles until unacceptable toxicity, disease progression, initiation of alternative anticancer therapy, or other reasons for participant withdrawal. MEDI-575 alone continued in those participants who achieved stable disease or better at the completion of carboplatin/paclitaxel therapy and did not demonstrate toxicity to MEDI-575.
Primary Outcome Measure Information:
Title
Number of Participants With Dose Limiting Toxicities (DLT): Phase 1b
Description
A DLT was defined as:
Any treatment-related Grade 3 or higher non-hematologic toxicity that occurred during the DLT assessment period with the following exceptions:
Grade 3 fever (in the absence of neutropenia) defined as more than (>) 40.0 degree Celcius (> 104.0 degree Fahrenheit) that resolved to normal or baseline within 24 hours of treatment and was not considered a serious adverse event (SAE); or
Grade 3 rigors/chills that responded to optimal therapy.
Any treatment-related Grade 3 or higher hematologic toxicity.
Time Frame
From Day 1 to Day 21 of first cycle
Title
Progression Free-Survival (PFS)
Description
Progression-free survival defined as the time from randomization (randomization referred to the date of treatment assignment) to disease progression (defined according to Response Evaluation Criteria for Solid Tumors [RECIST] version 1.1 guidelines) or death due to any cause, whichever occurs first. Participants without progression or death at the time of analysis were censored at their last date of tumor evaluation. PFS was assessed only in North America/European Union (EU) participants. Progression-free survival was evaluated using Kaplan-Meier method.
Time Frame
From randomization until the end of study (14 months from last participant enrolled or sponsor stopped the study), assessed at every 6 weeks until disease progression and every 3 months until the end of the study (approximately 3 years)
Secondary Outcome Measure Information:
Title
Best Overall Response
Description
Best overall response of a participant was defined as the best tumor response [Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD)] observed during the trial period assessed according to the Response Evaluation Criteria for Solid Tumors (RECIST) version 1.1 criteria. The participant's best overall response assignment depended on the findings of both target and non-target disease and also on the appearance of new lesions. CR was defined as disappearance of tumor lesions, PR was defined as a decrease of at least 30 percent (%) in the sum of diameters of target lesion, SD was defined as steady state of disease, and PD was defined as an increase of at least 20% in the sum of diameters of target lesions.
Time Frame
From initiation of treatment until the end of study (14 months from last participant enrolled or sponsor stopped the study), assessed at every 6 weeks until disease progression and every 3 months until the end of the study (approximately 3 years)
Title
Objective Response Rate (ORR)
Description
The ORR defined as the percentage of participants with confirmed CR or confirmed PR according to RECIST version 1.1 guidelines. Confirmed responses were those that persist on repeat imaging or assessment greater than or equal to (>=) 4 weeks after the initial documentation of response. The ORR was evaluated using Kaplan-Meier method.
Time Frame
From initiation of treatment until the end of study (14 months from last participant enrolled or sponsor stopped the study), assessed at every 6 weeks until disease progression and every 3 months until the end of the study (approximately 3 years)
Title
Time to Response (TTR)
Description
The TTR was measured from initiation of study treatment to the first documentation of objective response (OR). The OR defined as the participants with confirmed CR or confirmed PR according to RECIST version 1.1 guidelines. Confirmed responses were those that persist on repeat imaging or assessment >=4 weeks after the initial documentation of response. The TTR was evaluated using Kaplan-Meier method.
Time Frame
From initiation of treatment until the end of study (14 months from last participant enrolled or sponsor stopped the study), assessed at every 6 weeks until disease progression and every 3 months until the end of the study (approximately 3 years)
Title
Duration of Response (DR)
Description
The DR defined as the duration from the first documentation of OR to the first documented disease progression. Participants without progression at the time of analysis were censored at their last date of tumor evaluation. The DR was evaluated using Kaplan-Meier method.
Time Frame
From initiation of treatment until the end of study (14 months from last participant enrolled or sponsor stopped the study), assessed at every 6 weeks until disease progression and every 3 months until the end of the study (approximately 3 years)
Title
Time to Progression (TTP)
Description
The TTP was measured from randomization until the documentation of disease progression. Disease progression defined according to RECIST version 1.1 guidelines. Participants without progression at the time of analysis were censored at their last date of tumor evaluation. The TTP was evaluated using Kaplan-Meier method.
Time Frame
From initiation of treatment until the end of study (14 months from last participant enrolled or sponsor stopped the study), assessed at every 6 weeks until disease progression and every 3 months until the end of the study (approximately 3 years)
Title
Overall Survival (OS)
Description
Overall survival defined as the time from initiation of study treatment until death due to any cause. Participants who were still alive at the time of analysis were censored at their last date of last contact. The OS was evaluated using Kaplan-Meier method.
Time Frame
From initiation of treatment until the end of study (14 months from last participant enrolled or sponsor stopped the study), assessed at every 6 weeks until disease progression and every 3 months until the end of the study (approximately 3 years)
Title
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description
An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Time Frame
From signing of informed consent form until 90 days post the last dose treatment (approximately 3 years)
Title
Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs
Description
Laboratory investigations included hematology, coagulation, serum chemistry and urinalysis parameters. Participants with abnormalities in these laboratory investigations recorded as AEs or SAEs were reported.
Time Frame
From signing of informed consent form until 90 days post the last dose treatment (approximately 3 years)
Title
Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as AEs
Description
The 12-lead ECG data were performed and obtained in triplicate that is 3 ECGs obtained within a 5 minute time period. Number of participants with ECG abnormalities were reported and recorded as AEs.
Time Frame
From signing of informed consent form until 90 days post the last dose treatment (approximately 3 years)
Title
Maximum Observed Serum Concentration (Cmax) of MEDI-575 After First Dose
Description
The Cmax of MEDI-575 after first dose is reported.
Time Frame
Day 1 (pre-infusion and end of infusion), Day 2 (24 hours post Day 1 infusion), Day 8, and Day 15
Title
Time of Maximal Observed Concentration (Tmax) of MEDI-575 After First Dose
Description
The tmax refers to the time after dosing when a drug attains its highest measurable concentration (Cmax). The Tmax of MEDI-575 after first dose is reported.
Time Frame
Day 1 (pre-infusion and end of infusion), Day 2 (24 hours post Day 1 infusion), Day 8, and Day 15
Title
Area Under the Concentration-Time Curve Over the Dosing Interval (AUCtau) of MEDI-575 After First Dose
Description
The AUCtau defined as area under the plasma concentration time profile from time zero to the end of the dosing interval (tau). The AUCtau of MEDI-575 after first dose is reported.
Time Frame
Day 1 (pre-infusion and end of infusion), Day 2 (24 hours post Day 1 infusion), Day 8, and Day 15
Title
Maximum Serum Concentration at Steady State (Cmax,ss) of MEDI-575
Description
The Cmax,ss of MEDI-575 is reported.
Time Frame
Cycle 1 (pre-infusion and end of infusion on Day 1, Day 2, Day 8, and Day 15); Day 1 of Cycles 2 to 4 (pre-infusion and end of infusion)
Title
Time to Maximum Serum Concentration at Steady State (Tmax,ss) of MEDI-575
Description
The Tmax,ss of MEDI-575 is reported.
Time Frame
Cycle 1 (pre-infusion and end of infusion on Day 1, Day 2, Day 8, and Day 15); Day 1 of Cycles 2 to 4 (pre-infusion and end of infusion)
Title
Trough Serum Concentration at Steady State (Ctrough,ss) of MEDI-575
Description
The Ctrough,ss of MEDI-575 is reported.
Time Frame
Cycle 1 (pre-infusion and end of infusion on Day 1, Day 2, Day 8, and Day 15); Day 1 of Cycles 2 to 4 (pre-infusion and end of infusion)
Title
Percentage of Participants With Positive Anti-MEDI-575 Antibodies
Description
Immunogenicity assessment included determination of anti-drug (MEDI-575) antibodies in serum samples.
Time Frame
Day 1 (prior to infusion) of Cycles 1 to 7 (21-day cycle), end of treatment, 30 and 60 days after the last dose (approximately 3 years)
Title
Number of Participants With Platelet-derived Growth Factor Receptor Alpha (PDGFRα) Expression in Tumor Cells of Archived Tumor Samples
Description
The immunohistochemical expression of PDGFRα in tumor cells in archived formalin-fixed paraffin-embedded tissue samples collected at baseline are reported. The transmembrane receptor tyrosine kinase PDGFRα plays an important role in human carcinogenesis, both as a direct target on tumor cells and also as a mediator of stromal support for cancer cell growth. The data of positive-staining tumor cells are reported in 3 categories: intensity (1+ [weak expression, staining in <5 % of tumor cells]; 2+ [moderate expression, staining in >= 5 % of tumor cells]; and 3+ [strong expression, staining in >5 % of the tumor cells]), localization (membranous, cytoplasmic, or nuclear), and frequency (rare, occasional, or frequent).
Time Frame
Baseline (Screening [Days -28 to -1])
Title
Number of Participants With PDGFRα Expression in Stromal Cells of Archived Tumor Samples
Description
The immunohistochemical expression of PDGFRα in stromal cells in archived formalin-fixed paraffin-embedded tissue samples collected at baseline are reported. The transmembrane receptor tyrosine kinase PDGFRα plays an important role in human carcinogenesis, both as a direct target on tumor cells and also as a mediator of stromal support for cancer cell growth. The data of positive-staining stromal cells are reported in 3 categories: intensity (1+ [weak expression, staining in <5 % of tumor cells]; 2+ [moderate expression, staining in >= 5 % of tumor cells]; and 3+ [strong expression, staining in >5 % of the tumor cells]), localization (membranous, cytoplasmic, or nuclear), and frequency (rare, occasional, or frequent).
Time Frame
Baseline (Screening [Days -28 to -1])
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically confirmed inoperable Stage IIIB or Stage IV non-small cell lung cancer according to the Seventh Edition of the American Joint Committee on Cancer (AJCC) Tumor Node Metastases (TNM) staging system (only participants with squamous cell carcinoma will be enrolled)
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Life expectancy of greater than or equal to (>=) 3 months
Prothrombin time elevation less than or equal to (<=) Grade 2 by National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) criteria (Version 4.0) is acceptable for participants on anticoagulant therapy
Adequate hematologic function
Adequate organ function
Suitable candidates for therapy with carboplatin/paclitaxel
Participants must have at least 1 lesion that is measurable using Response Evaluation Criteria for Solid Tumors
Participants must be willing to consent to allow collection of archived NSCLC tumor samples
Negative serum beta-human chorionic gonadotropin (beta-hCG) test (women of childbearing potential only)
Females of childbearing potential, unless surgically sterile has a sterile male partner, is premenarchal or at least 2 years postmenopausal, or practices abstinence, must use 2 effective methods of avoiding pregnancy (including oral, transdermal, or implanted contraceptives, intrauterine device, female condom with spermicide, diaphragm with spermicide, cervical cap, or use of a condom with spermicide by the sexual partner) from screening, and must agree to continue using such precautions for 90 days after the final dose of treatment; cessation of birth control after this point should be discussed with a responsible physician
Males, unless surgically sterile, must use 2 effective methods of birth control with a female partner and must agree to continue using such contraceptive precautions from screening through 90 days after the final dose of treatment
Exclusion Criteria:
At discretion of the investigator regarding safety of the participants
Concurrent enrollment in another clinical study
Any concurrent chemotherapy, radiotherapy, immunotherapy, biologic, or hormonal therapy for treatment of cancer
Previous monoclonal antibody (mAb) treatment specifically directed against platelet-derived growth factor (PDGF) or PDGF receptors
History of serious allergy or reaction to any component of the MEDI-575 formulation
Receipt of any previous systemic anticancer therapies for advanced or metastatic disease
Previous adjuvant/neoadjuvant radiotherapy or chemotherapy for treatment of previous nonmetastatic disease is allowed provided that 6 months have elapsed from the end of such therapies to the time of enrollment
New York Heart Association >= Class II congestive heart failure
History of myocardial infarction, unstable angina, transient ischemic attack or stroke within the previous 6 months prior to enrollment
History of other invasive malignancy within 5 years except for cervical carcinoma in situ (CIS), non-melanomatous carcinoma of the skin or ductal carcinoma in situ (DCIS) of the breast that have been surgically cured
Evidence of active infection requiring the use of systemic antimicrobial treatment within 72 hours prior to initial treatment with MEDI-575
Use of immunosuppressive medication (inhaled and topical corticosteroids are permitted) within 7 days prior to enrollment
Systemic immunosuppressive steroid therapy
Participants may take replacement doses of steroids if on a stable dose for at least 2 weeks prior to enrollment
History of active human immunodeficiency virus (HIV) or active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
Pregnancy or lactation
Previous medical history or evidence of an inter-current illness
Any physical, social, or psychiatric condition which would prevent effective cooperation or participation in the study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
MedImmune LLC
Organizational Affiliation
MedImmune LLC
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Fountain Valley
State/Province
California
ZIP/Postal Code
92708
Country
United States
Facility Name
Research Site
City
Oxnard
State/Province
California
ZIP/Postal Code
93030
Country
United States
Facility Name
Research Site
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Research Site
City
Lafayette
State/Province
Indiana
ZIP/Postal Code
47905
Country
United States
Facility Name
Research Site
City
Baton Rouge
State/Province
Louisiana
ZIP/Postal Code
70809
Country
United States
Facility Name
Research Site
City
Annapolis
State/Province
Maryland
ZIP/Postal Code
21401
Country
United States
Facility Name
Research Site
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21204
Country
United States
Facility Name
Research Site
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21231
Country
United States
Facility Name
Research Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Research Site
City
Danvers
State/Province
Massachusetts
ZIP/Postal Code
01923
Country
United States
Facility Name
Research Site
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Research Site
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68144
Country
United States
Facility Name
Research Site
City
Lake Success
State/Province
New York
ZIP/Postal Code
11042
Country
United States
Facility Name
Research Site
City
Canton
State/Province
Ohio
ZIP/Postal Code
44718
Country
United States
Facility Name
Research Site
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
17033-0850
Country
United States
Facility Name
Research Site
City
Hilton Head Island
State/Province
South Carolina
ZIP/Postal Code
29926
Country
United States
Facility Name
Research Site
City
Chattanooga
State/Province
Tennessee
ZIP/Postal Code
37404
Country
United States
Facility Name
Research Site
City
Corpus Christi
State/Province
Texas
ZIP/Postal Code
78404
Country
United States
Facility Name
Research Site
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Research Site
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H 8L6
Country
Canada
Facility Name
Research Site
City
Marseille cedex
ZIP/Postal Code
13915
Country
France
Facility Name
Research Site
City
Berlin
ZIP/Postal Code
12351
Country
Germany
Facility Name
Research Site
City
Szombathely
ZIP/Postal Code
9700
Country
Hungary
Facility Name
Research Site
City
Fukuoka-shi
ZIP/Postal Code
811-1347
Country
Japan
Facility Name
Research Site
City
Sunto-gun
ZIP/Postal Code
411-8777
Country
Japan
Facility Name
Research Site
City
Gdansk
ZIP/Postal Code
80-952
Country
Poland
Facility Name
Research Site
City
Lodz
ZIP/Postal Code
90-242
Country
Poland
Facility Name
Research Site
City
Mrozy
ZIP/Postal Code
05-320
Country
Poland
Facility Name
Research Site
City
Szczecin
ZIP/Postal Code
70-891
Country
Poland
12. IPD Sharing Statement
Learn more about this trial
A Study of Carboplatin and Paclitaxel With or Without MEDI-575 in Untreated, Advanced Non-Small Cell Lung Cancer
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