E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Previously untreated advanced non-small cell lung cancer in adults |
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E.1.1.1 | Medical condition in easily understood language |
Previously untreated advanced non-small cell lung cancer in adults |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10029522 |
E.1.2 | Term | Non-small cell lung cancer stage IV |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10029521 |
E.1.2 | Term | Non-small cell lung cancer stage IIIB |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Evaluation of progression-free survival of subjects following treatment with MEDI-575 when used in combination with paclitaxel/carboplatin versus paclitaxel/carboplatin alone in subjects with previously untreated, advanced non-small cell lung cancer |
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E.2.2 | Secondary objectives of the trial |
Five secondary objectives:
1. To evaluate other antitumor activities of MEDI-575 when used in combination with paclitaxel/carboplatin
2. To describe the safety and tolerability of MEDI-575 when used in combination with carboplatin/paclitaxel
3. To determine the immunogenicity of MEDI-575
4. To describe the pharmacokinetics of MEDI-575 in combination with paclitaxel/carboplatin
5. To determine the expression of platelet-derived growth factor alpha in the tumor cells and stroma of archived tumor samples. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subjects must meet all the following criteria:
Age 18 years or older at the time of screening,
Written informed consent and any locally required authorization,
Histologically confirmed inoperable Stage IIIB or Stage IV non-small cell lung cancer
ECOG performance status of 0 or 1,
Life expectancy of ≥ 3 months,
Prothrombin time elevation ≤ Grade 2 is acceptable for subjects on anticoagulant therapy,
Adequate hematologic and organ function,
Suitable candidates for therapy with carboplatin/paclitaxel,
Subjects must have at least 1 lesion that is measurable using RECIST,
Subjects must be willing to consent to allow collection of archived NSCLC tumor samples,
Adequate contraception from screening through end of trial
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E.4 | Principal exclusion criteria |
Any of the following would exclude the subject from participation in the study:
Concurrent enrollment in another clinical study,
Employees of the clinical study site or any other individuals involved with the conduct of the study, or immediate family members of such individuals,
Any concurrent chemotherapy, radiotherapy, immunotherapy, biologic, or hormonal therapy for treatment of cancer,
Previous monoclonal antibody treatment,
History of serious allergy or reaction to any component of the MEDI-575 formulation,
Receipt of any previous anticancer therapies,
(Previous adjuvant/neoadjuvant radiotherapy or chemotherapy is allowed)
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,
Use of immunosuppressive medication within 7 days prior to enrollment,
Systemic immunosuppressive steroid therapy,
History of active human immunodeficiency virus (HIV) or active hepatitis virus infection (HBV, HCV),
Known brain metastases,
Clinically significant abnormality on ECG
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint for efficacy is PFS. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Measured from randomization until the documentation of disease progression or death due to any cause, whichever occurs first, based on blinded central independant imaging review of response and disease progression. Imaging to occur at baseline then every 2 cycles (ie, every 6 weeks) beginning with cycle 3 |
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E.5.2 | Secondary end point(s) |
Assessment of antitumor activity:
•ORR, TTR, DR, TTP, OS, and change in tumor size.
Safety endpoints:
•Collection of AEs and SAEs. Also, changes in clinical laboratory, and ECG evaluations from baseline
Immunogenicity:
•By summarizing number and percentage of subjects who develop detectable anti-MEDI-575 antibodies
PK Assessment:
•Assessed using parameters including Cmax, Tmax, and AUCĪ after the first dose. MEDI-575 steady state PK parameters include Cmaxss, Cminss, and Tmaxss
Expression of PDGFRalpha:
•Determination of expression of PDGFRalpha in tumor tissue
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Antitumor activity:
•OS determined as time from randomization until death due to any cause. ORR, TTR, DR, TTP, and change in tumor size will be assessed based on imaging review of response and progression.
Safety endpoints:
•AEs and SAEs occurring from time written IC is obtained continuously through 90 days post last dose or until subject begins another anticancer therapy. Changes from baseline in clinical laboratory and ECG evaluations will be assessed from results collected on study visits.
Immunogenicity:
•Assessed prior to infusion on Day 1 of each cycle as well as at the EOT and during follow up.
PK:
•Each study visit day throughout all cycles.
Expression of PDGFRalpha:
•Archived tissue will be collected prior to Day1 of the first cycle for expression analysis
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 6 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
Japan |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of the study (“study completion”) is defined as the date of the last protocol-specified visit/assessment (including telephone contact) for the last subject in the study. This date will be 14 months after the last subject is entered into the trial or when the sponsor stops the study. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |