E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Stage IIIB/IV Non-small Cell Lung Cancer |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10029521 |
E.1.2 | Term | Non-small cell lung cancer stage IIIB |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10029522 |
E.1.2 | Term | Non-small cell lung cancer stage IV |
|
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 |
The primary objective of this study is to evaluate the progression-free survival (PFS) rate at 6 months of IMC-1121B administered in combination with paclitaxel and carboplatin as first-line therapy for Stage IIIB/IV non-small cell lung cancer (NSCLC). |
|
E.2.2 | Secondary objectives of the trial |
· Evaluate the safety profile of IMC-1121B in combination with paclitaxel and carboplatin · Determine the objective response rate (ORR) · Determine the duration of response · Determine the overall survival (OS) rate at 1-year · Determine the progression-free survival · Determine the overall survival · Assess the pharmacokinetic profile and immunogenicity of IMC-1121B |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. The patient has histologically or cytologically confirmed NSCLC. Mixed NSCLC tumors will be categorized by the predominant cell type. Cytologic or histologic elements can be established on metastatic tumor aspirates or biopsy. For squamous histology or for centrally located mediastinal masses (< 3 cm from the carina) identified by computed tomography scan (CT) or chest X-ray, the patient must undergo a magnetic resonance imaging (MRI) of the chest or intravenous contrast CT scan within 4 weeks of anticipated study entry, to exclude major airway or blood vessel invasion (in the investigator’s opinion) by cancer.
2. The patient has advanced NSCLC (Stage IIIB not suitable for radiation therapy or chemoradiotherapy at study entry, or Stage IV). Patients with an earlier stage of disease that has relapsed with a higher stage are eligible provided chemotherapy or radiation therapy for pre-relapsed disease was completed > 1 year prior to study entry.
3. The patient has measurable disease (as defined by Response Evaluation Criteria in Solid Tumors [RECIST], see Section 11 of protocol).
4. The patient’s ECOG performance status is ≤ 1.
5. The patient’s age at the time of study entry is ≥ 18 years.
6. The patient has adequate hematologic function as defined by an absolute neutrophil count (ANC) ≥ 1500/μL, hemoglobin ≥ 9 g/dL, and a platelet count ≥ 100,000/μL obtained within 2 weeks prior to the first dose of study medication.
7. The patient has adequate hepatic function as defined by a total bilirubin ≤ 1.5 mg/dL (except for known Gilbert’s disease) and transaminases and alkaline phosphatase ≤ 5 x the upper limit of normal (ULN) obtained within 2 weeks prior to the first dose of study medication.
8. The patient has adequate renal function as defined by serum creatinine ≤ 1.5 x ULN or calculated creatinine clearance (CrCl) > 60 mL/minute, and urine dipstick for protein < 1+ (ie, either 0 or trace) obtained within 2 weeks prior to the first dose of study medication. If urine dipstick is ≥ 1+, a 24-hour urine for protein must demonstrate < 500 mg of protein in 24 hours to allow participation in the study.
9. The patient has adequate coagulation function, as defined by international normalized ratio (INR) ≤ 1.5 and a partial thromboplastin time (PTT) ≤ 5 seconds above ULN if not receiving anticoagulation therapy. Patients on full-dose anticoagulation must be on a stable dose of oral anticoagulant or low molecular weight heparin, and if on warfarin must have therapeutic INR and have no active bleeding (defined as within 14 days of first dose of study medication) or pathological condition that carries a high risk of bleeding (eg, tumor involving major vessels or known varices).
10. The patient agrees to use adequate contraception during the study period and for 4 weeks after the last dose of study medication.
11. The patient has provided signed informed consent.
|
|
E.4 | Principal exclusion criteria |
1. The patient has untreated central nervous system (CNS) metastases. Patients with treated brain metastases are eligible if they have no evidence of Grade ≥ 1 CNS hemorrhage based on pretreatment MRI or intravenous contrast CT scan (performed within 28 days prior to the first dose of IMC-1121B), are clinically stable with regard to neurologic function, and are off all steroids after cranial irradiation (whole brain radiation therapy, focal radiation therapy, stereotactic radiosurgery) ending at least 2 weeks prior to the first dose of IMC-1121B, or after surgical resection performed at least 4 weeks prior the first dose of IMC 1121B.
2. The patient received prior bevacizumab therapy.
3. The patient has radiologically documented evidence of major blood vessel invasion or encasement by cancer.
4. The patient received prior systemic chemotherapy for Stage IIIB/IV NSCLC.
5. The patient received prior systemic chemotherapy or radiation therapy for Stage I-IIIA NSCLC < 1 year prior to the first dose of study medication.
6. The patient has any concurrent malignancy other than basal cell skin cancer, or carcinoma in situ of the cervix. Patients with adequately treated cancers of other histologies who have been disease-free for more than 3 years prior to the first dose of study medication are eligible.
7. The patient is receiving concurrent treatment with other anticancer therapy, including other chemotherapy, immunotherapy, hormonal therapy, radiotherapy, chemoembolization, or targeted therapy.
8. The patient has an ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
9. The patient has uncontrolled thrombotic or hemorrhagic disorders.
10. The patient has poorly-controlled hypertension (ie, blood pressure in abnormal range despite medical management).
11. The patient is receiving chronic daily treatment with aspirin (> 325 mg/day) or other known inhibitors of platelet function.
12. Patients with a history of gross hemoptysis (defined as bright red blood or ≥ 1/2 teaspoon) within 2 months of entry into this trial.
13. The patient has had a serious non-healing wound, ulcer, or bone fracture within 28 days prior to first dose of study medication.
14. The patient has undergone major surgery with 28 days prior the first dose of study medication, or subcutaneous venous access device placement within 7 days prior to the first dose of study medication. Furthermore, any patients with post-operative bleeding complications or wound complications from surgical procedures performed in the last 2 months will be excluded.
15. The patient has an elective or a planned major surgery to be performed during the course of the trial.
16. The patient has peripheral neuropathy ≥ Grade 2 (National Cancer Institute Common Toxicity Criteria for Adverse Events, Version 3.0 [NCI-CTCAE v 3.0]).
17. The patient, if female, is pregnant or lactating.
18. Regardless of tumor histology, the patient has radiographic evidence of intratumor cavitation.
19. The patient has experienced any Grade 3-4 gastrointestinal bleeding within 3 months prior to study entry. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The PFS rate at 6 months is the proportion of patients that experience a PFS event during the first 6 months in the study. The PFS is defined as the time from date of first dose of study medication to the date of first documented disease progression as defined by RECIST, or death from any cause, whichever is first. Patients who die without a reported prior progression will be considered to have progressed on the day of their death. Frequency and percentage will be used to summarize the PFS rate at 6 months along with a 95% CI to be calculated for the ITT population. |
|
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 | No |
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 2 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 2 |
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 | Information not present in EudraCT |
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 |
|
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
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |