E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced nonsquamous non-small cell lung carcinoma |
|
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 | 10029522 |
|
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 hypothesis that cixutumumab given in combination with cisplatin and pemetrexed is superior to cisplatin and pemetrexed as first-line therapy for patients with advanced nonsquamous non-small cell lung carcinoma (NSCLC) as measured by progression-free survival (PFS). |
|
E.2.2 | Secondary objectives of the trial |
• to evaluate the hypothesis that cixutumumab given in combination with cisplatin and pemetrexed is superior to cisplatin and pemetrexed, as measured by the following: o Objective response rate (ORR) o Time to progressive disease (TTPD) o Change in tumor size (CTS) o Overall survival (OS) o Duration of response • to evaluate the safety profile of cixutumumab given in combination with cisplatin and pemetrexed • to assess the pharmacokinetic profile of cixutumumab (Arm B only) • to assess the immunogenicity of cixutumumab (Arm B only) • to assess the pharmacodynamic profile of cixutumumab, including: o potential surrogates of cixutumumab pharmacodynamic activity including, but not limited to, free IGF-I, total IGF-I, IGFBP-3 • to evaluate the time to worsening symptoms (TWS) as measured by Lung Cancer Symptom Scale (LCSS) scores (patient scale only) |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
[1] The patient has histologically or cytologically confirmed, nonsquamous (adenocarcinoma/large cell or other) NSCLC. [2] The patient has Stage IV disease (AJCC Staging Manual, Seventh Edition; Edge et al. 2010) at the time of study entry. [3] Patients with treated brain metastases are eligible if they are clinically stable with regard to neurologic function, off steroids after cranial irradiation (whole brain radiation therapy, focal radiation therapy, and stereotactic radiosurgery) ending at least 2 weeks prior to randomization, or after surgical resection performed at least 28 days prior to randomization. The patient may have no evidence of Grade ≥1 central nervous system (CNS) hemorrhage based on pretreatment magnetic resonance imaging (MRI) or intravenous (IV) contrast computed tomography (CT) scan (performed within 21 days before randomization). [4] The patient has measurable or nonmeasurable disease according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v. 1.1) guidelines (Eisenhauer et al. 2009; Attachment 6). [5] The patient is ≥18 years old. [6] The patient has an ECOG performance status (PS) of 0 or 1 (Oken et al. 1982; Attachment 7). [7] If the patient received prior adjuvant chemotherapy, the last dose of adjuvant treatment was administered at least 6 months prior to randomization. [8] The patient has adequate organ function, as evidenced by the following: • Adequate bone marrow reserve: absolute neutrophils (segmented and bands) count (ANC) ≥1500 cells/μL, hemoglobin ≥9.5 g/dL, and platelets ≥100000 cells/μL. • Hepatic: bilirubin ≤1.5 times the upper limit of normal (ULN), and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 times ULN (or ≤5 times the ULN in the presence of known liver metastases). • Renal: The patient has adequate renal function as defined by serum creatinine ≤1.2 times the institutional ULN. If serum creatinine is above 1.2 times the ULN, the patient’s creatinine clearance must be ≥45 mL/min. [9] The patient has fasting serum glucose ≤100 mg/dL, and hemoglobin A1C ≤6%. If baseline nonfasting glucose ≤100 mg/dL, fasting glucose measurement is not required. [10] Females with reproductive potential: Must have a negative serum or urine pregnancy test within 7 days prior to the first dose of any study drug. [11] Males and females with reproductive potential: Must agree to use medically approved contraceptive precautions during the study and for 6 months following the last dose of any study drug. [12] The patient has the ability to understand and the willingness to sign a written informed consent form (ICF). [13] Patients with prior radiation therapy may be eligible for this study if they meet the following guidelines: • Previous radiation therapy is allowed to <25% of the bone marrow (Cristy and Eckerman 1987), but should have been limited and must not have included whole pelvis radiation. • Patients must have recovered from the toxic effects of the treatment prior to study enrollment (except for alopecia). • Prior thoracic radiotherapy must be completed 30 days before study enrollment. • Lesions that have been radiated cannot be included as sites of measurable disease unless clear tumor progression has been documented in these lesions since the end of radiation therapy. • Palliative extrathoracic radiotherapy to preexisting lesions may continue on study; however, these lesions may not be included as sites of measurable disease. [14] The patient has archived tumor tissue available for analysis (can be either primary tumor or metastases; minimum of 5 slides). [15] The patient has an estimated life expectancy of at least 12 weeks. |
|
E.4 | Principal exclusion criteria |
Patients must not have an uncontrolled intercurrent illness, leptomeningeal disease, or active infection requiring parenteral therapy. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary objective of this study is to evaluate the hypothesis that cixutumumab given in combination with cisplatin and pemetrexed is superior to cisplatin and pemetrexed as first-line therapy for patients with advanced nonsquamous non-small cell lung carcinoma (NSCLC) as measured by progression-free survival (PFS). |
|
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 | No |
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 | Yes |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 29 |
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
|
Ultima visita dell`ultimo paziente attesa 9 mesi dopo l`ultimo paziente randomizzato |
|
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 | 0 |
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 | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |