E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastic Non-Small Cell Lung Cancer |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10059515 |
E.1.2 | Term | Non-small cell lung cancer metastatic |
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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 | 10029515 |
E.1.2 | Term | Non-small cell lung cancer recurrent |
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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 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10029522 |
E.1.2 | Term | Non-small cell lung cancer stage IV |
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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 |
•To determine whether addition of CP-751,871 prolongs the survival of NSCLC patients treated with gemcitabine and cisplatin. |
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E.2.2 | Secondary objectives of the trial |
Assess progression free survival in each arm; • Assess the overall response rate in each arm; • Evaluate the safety and tolerability of CP-751,871 in combination with gemcitabine and cisplatin; • Assess health-related quality of life outcomes (HRQoL) and health status in both treatment arms; • Collect pharmacokinetic data of CP-751,871 for population pharmacokinetic meta-analysis; • Monitor for the occurrence of anti-drug antibody (ADA) response to CP-751,871 treatment; • Biomarker analysis of the IGF-IR pathway in blood and tumor (upon patient consent) samples. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Histologically or cytologically confirmed diagnosis of Non-Small Cell Lung Cancer with a primary histological classification of squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma. Lung tumor with a primary diagnosis of small cell, large cells, carcinoid, sarcomatoid, salivary gland or unspecified (Unknown, Not Otherwise Specified - NOS) are excluded; 2. Advanced NSCLC with documented Stage IIIB (with pleural effusion) or Stage IV or recurrent disease; 3. At least 3 weeks since major surgery prior to randomization and with resolution of all acute toxicities to CTC Grade ≤1 (NCI CTCAE v3.0) or deemed irreversible by investigator (minor surgery such as drainage for Pleural Effusion may require shorter recovery time and don’t prevent patient entry into the study); 4. At least 2 weeks since the completion of radiation therapy prior to randomization and with resolution of all acute toxicities to CTC Grade ≤1 (NCI CTCAE v3.0) or deemed irreversible by investigator; 5. Males or females aged ≥18 years; 6. ECOG performance status (PS) 0 or 1; 7. Adequate organ function as determined by the following criteria. These must be determined within 7 days prior to enrollment. Strict adherence to these criteria is required; exceptions will not be made; a. Absolute neutrophil count (ANC) ≥1.5 x 10^9/L; b. Platelet count ≥75 x 10^9/L; c. Haemoglobin ≥8 g/dl; d. Serum creatinine ≤1.5 x upper limit of normal (ULN); e. Serum aspartate aminotransferase (AST; serum glutamate-oxalate transferase [SGOT]) and serum alanine aminotransferase (ALT; serum glutamate-pyruvate transferase [SGPT]) ≤2.5 x ULN, or ≤5 x ULN if liver abnormalities are due to underlying malignancy; f. Total bilirubin ≤1.5 x ULN. 8. Female patients must not be pregnant or nursing. Female patients or their partners must be surgically sterile or be postmenopausal, or must agree to use effective contraception while receiving study treatment and for at least 5 months thereafter (or longer if required by local regulation). All female patients with reproductive potential must have a negative pregnancy test (serum/urine) within the 72 hours prior to starting treatment. Male patients with partners of childbearing potential must be surgically sterile or must agree to use effective contraception while receiving study treatment and for at least 5 months thereafter (or longer if required by local regulation). The definition of effective contraception should be in agreement with local regulation and based on the judgment of the principal investigator or a designated associate. 9. Written, voluntary, signed and dated informed consent document indicating that the subject (or legally acceptable representative) has been informed of all pertinent aspects of the trial before enrollment must be provided. 10. Patient must be willing and able to comply with scheduled visits, treatment plans, laboratory tests and other study procedures, including completion of patient-reported outcome (PRO) measures. |
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E.4 | Principal exclusion criteria |
1. No prior systemic treatment for NSCLC, except for adjuvant/neo-adjuvant chemotherapy. Adjuvant/neoadjuvant chemotherapy must have been completed ≥12 months prior to randomization. 2. Patients with symptomatic central nervous system (CNS) metastases are not permitted. a. Patients with symptoms suggestive of CNS metastases must undergo radiologic evaluation at baseline to rule out metastases; b. Patients with known, asymptomatic CNS lesions are permitted; c. Patients with stable, treated brain metastasis (eg, whole brain radiation therapy or similar) are permitted (provided they are not on corticosteroids therapy). 3. No acute or chronic medical or psychiatric condition or laboratory abnormality that could increase the risk associated with study participation or study drug administration or could interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into the study. This includes but is not limited to: a. Uncontrolled hypertension, uncontrolled diabetes (defined as a Hgb A1C level >8%), unstable angina, myocardial infarction or symptomatic congestive heart failure within the past 12 months or serious uncontrolled cardiac arrhythmia; b. Uncontrolled superior vena cava syndrome; c. Active bacterial, fungal or viral infection including hepatitis B (HBV), hepatitis C (HBC) and human immunodeficiency virus (HIV). Serological testing will not be required at baseline for patients who have no symptoms suggestive of infection but is required for patients who do; d. Pre-existing peripheral neuropathy > CTCAE Grade 2; e. Dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent or compliance with the requirements of the protocol. 4. No use of any concomitant medication that could increase the risk associated with study participation or study drug administration or could interfere with the interpretation of study results. This includes but is not limited to: a. Requirement for chronic treatment with therapeutic doses of systemic corticosteroids or use of high-dose corticosteroids (≥100 mg of prednisone per day or >40 mg dexamethasone per day) within 1 week prior to treatment. Previous steroid treatment or low dose steroid use for the control of nausea and vomiting will be allowed. The use of corticosteroids for the prophylaxis or treatment of nausea and vomiting, or as chemotherapy pre-medication, will be allowed at the discretion of the investigator; b. Previous or concurrent therapy with any IGF-IR inhibitor. Requirement for use of growth hormone agonist or antagonist, or use of aminoglycoside (which could potentiate cisplatin nephrotoxicity); 5. Patients may not have known or suspected hypersensitivity to any of the study drugs (gemcitabine, cisplatin, or CP-751,871), study drug classes (platinum, nucleoside analogues) or excipients in the formulation of study drugs. 6. Patients must not have been admitted to an institution by virtue of an order issued by either the judicial or administrative authorities. 7. Enrollment in another concurrent therapeutic clinical trial is not permitted. 8. No other active invasive malignancies (previous malignancies are allowed if occurred ≥3 years prior to randomization or current in situ malignancies like in situ carcinoma of the cervix of the uterus or basal or squamous cell carcinoma of the skin). |
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E.5 End points |
E.5.1 | Primary end point(s) |
Overall survival defined as the time period from randomization to death due to any cause. |
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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 | No |
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 | 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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | 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) | 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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 118 |
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 |
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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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As per protocol see section 6.4 and Section 7.1.1 |
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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 | 8 |
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 | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |