E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Primary Objective: Determine whether the addition of CP-751,871, an IGF-1R inhibitor, in combination with paclitaxel plus carboplatin prolongs survival in patients with non-adenocarcinoma NSCLC. |
|
E.2.2 | Secondary objectives of the trial |
Secondary Objectives: • Assess progression free survival in each arm; • Evaluate the safety and tolerability of CP-751,871 in combination with paclitaxel and carboplatin; • Assess the overall response rate in each arm; • Assess health-related quality of life outcomes (HRQoL) and health states in both treatment arms; • Collect pharmacokinetic data of CP-751,871 for population pharmacokinetic meta-analysis; • Monitor for the occurrence of any anti-drug antibody in response to CP-751,871 treatment; • Explore the association pretreatment IGF-1 and change in IGF-1 with survival; • Collection of anonymized samples for molecular profiling |
|
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 histology of predominantly squamous cell, large cell or adenosquamous carcinoma. 2. Advanced NSCLC with documented Stage IIIB (with pleural effusion) or Stage IV or recurrent disease 3. No prior systemic treatment for NSCLC, except for adjuvant chemotherapy. Adjuvant chemotherapy must have completed ≥12 months prior to randomization 4. Prior surgery or radiation therapy is permitted if completed at least 3 weeks prior to randomization and all acute toxicities have resolved to CTC Grade 1 (NCI CTCAE v3.0) 5. Age ≥18 years 6. ECOG performance status (PS) 0 or 1 7. Adequate organ function as determine by the following criteria. a. Absolute neutrophil count (ANC) ≥1.5 x 109/L b. Platelet count ≥75 x 109/L c. Hemoglobin ≥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]) ≤5 x ULN, or ≤10 x ULN if liver abnormalities are due to underlying malignancy f. Total bilirubin ≤1.25 x ULN 8. Female patients may 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. All female patients with reproductive potential must have a negative pregnancy test (serum/urine) within the 72 hours prior to starting treatment. Male patients or their partners must be surgically sterile or must agree to use effective contraception while receiving study treatment and for at least 5 months thereafter. The definition of effective contraception will be based on the judgment of the principal investigator or a designated associate 9. Written, voluntary informed consent must be provided a. Patients with symptoms suggestive of CNS metastases must undergo radiologic evaluation to rule out metastases b. Patients with known, asymptomatic CNS lesions are permitted 10.Patients with symptomatic central nervous system (CNS) metastases are not permitted. Patients with symptoms suggestive of CNS metastases must undergo radiologic evaluation to rule out metastases Patients with known, asymptomatic CNS lesions are permitted Patients with stable, treated brain metastasis (e.g. whole brain radiation therapy or similar) are permitted (off steroid medication) 11. 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: 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 premedication, will be allowed at the discretion of the investigator b. 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 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 d. Pre-existing peripheral neuropathy > CTC 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 12. No other active malignancies (other than non-adenocarcinoma NSCLC) 13. Patients may not have known or suspected hypersensitivity to any of the study drugs (paclitaxel, carboplatin or CP-751,871), study drug classes (taxane, platinum) or excipients in the formulation of study drugs (including castor oil and derivatives such as Cremophor®) 14. 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
|
|
E.4 | Principal exclusion criteria |
Patients with a primary histology of adenocarcinoma NSCLC and those with unknown or unspecified (Not otherwise specified) NSCLC histology will be excluded Patients with symptomatic central nervous system (CNS) metastases are not permitted. Enrollment in another therapeutic clinical trial is not permitted Previous or concurrent therapy with any IGF1R inhibitor, growth hormone agonist or antagonist is not permitted
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is overall survival defined as the time from Randomization to the date of death due to any cause.
|
|
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 | 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
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 60 |
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 | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |