| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Advanced NSCLC of non-adenocarcinoma histology |
|
| 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 | 10025055 |
| E.1.2 | Term | Lung cancer non-small cell 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 |
| To compare OS in patients with advanced NSCLC of non- adenocarcinoma tumor histology receiving erlotinib alone (Arm B) or CP-751,871 plus erlotinib (Arm A). Patients in Arm B may have received single agent CP-751,871 upon progression on erlotinib alone. |
|
| E.2.2 | Secondary objectives of the trial |
• To compare PFS in patients with advanced NSCLC of non-adenocarcinoma tumor histology receiving erlotinib alone (Arm B) or CP-751,871 plus erlotinib (Arm A). PFS will be tested for possible submission for accelerated approval consideration.
• To assess the safety and tolerability of multiple doses of CP-751,871;
• To assess the efficacy of CP-751,871 in terms of ORR;
• To collect PK data of CP-751,871 for population PK meta-analysis;
• To monitor for the occurrence of anti-drug antibody in response to CP-751,871;
• To test for the presence of Circulating Tumor Cells (CTCs) expressing the IGF-IR;
• To assess the differences in health state utilities using the EQ-5D.
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Male or females >18 years of age.
2. Histologically or cytologically documented non-small cell lung cancer with a primary histology of squamous cell, large cell or adenosquamous carcinoma and their variants (Appendix 10 of the protocol),68 with metastases (Stage IV or recurrent disease) or locally advanced (Stage IIIB) with malignant pleural effusion.
3. Patients in whom erlotinib is a reasonable treatment option. Patient must have received previous treatment for advanced disease consisting of at least one platinum based combination regimen. However, patients 70 years of age or older could have received at least one single agent therapies. In countries in which docetaxel or premetexed are routinely used and available in standard practice, patients will have
been treated previously with, or have a significant known contraindication to one or both of these agents.
4. At least 1 measurable lesion, as defined by RECIST. All target lesions must have a unidimensional diameter of at least 2 cm (1 cm is acceptable for spiral CT scans if the reconstruction algorithm is 0.5 cm). Baseline measurements/evaluations must be completed within 4 weeks prior to randomization and performed at the participating investigational site.
5. ECOG performance status 0-2.
6. At least two weeks since the last systemic therapy regimen prior to enrollment. Patients must have recovered to NCI CTCAE v3.0 <Grade 1 from all acute toxicities (excluding Grade 1 toxicity that are not considered a safety risk by the Sponsor and Investigator) or toxicity must be deemed irreversible by the investigator.
7. At least one week since the last radiotherapy. Patients must have recovered from all acute toxicities from radiotherapy.
8. Patients must have adequate hematologic, renal and liver function as defined by:
Hemoglobin >9 g/dL, neutrophils >1000/mm3, platelets >50000/mm3, creatinine
<2 mg/mL, and AST (SGOT) and/or ALT (SGPT) <5 x ULN (upper limit of normal).
9. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures, including the provision of diagnostic paraffin slides or sections and the completion of patient reported outcome measures.
10. Negative pregnancy test within one week of initial dose of CP-751,871 for women of child-bearing potential. Patients must be surgically sterile or postmenopausal women, or must agree to use double barrier contraception during the period of therapy and for 5 months following the last dose of the study drug. Double barrier contraception is defined as male condom plus spermicide in combination with a female condom, diaphragm, or cervical cap; or male condom plus spermicide in combination with an intrauterine device. Within these limits, the specific form of contraception employed is left to the discretion of the patient or the principal investigator.
11. Written and voluntary informed consent understood, signed and dated. |
|
| E.4 | Principal exclusion criteria |
1. Primary NSCLC histology not listed in Inclusion #1. Primary NSCLC adenocarcinoma and its subtypes: acinar, papillary, bronchioalveolar, solid, fetal,
mucinous, signet ring and clear cell or mixed histologies of these types. Unknown or unspecified (Not otherwise specified) NSCLC histology.
2. Prior erlotinib therapy.
3. Prior anti-IGF-IR based investigational therapy. Other investigational therapies (targeted or vaccine), unless otherwise agreed by investigators and sponsor, will require 2 weeks wash out period before enrollment.
4. Symptomatic brain metastases. Brain metastases stable for <2 weeks before dosing or requiring concurrent steroid therapy or with clinical symptoms. Clinical symptoms suggestive of new brain metastasis within 2 weeks of enrollment unless new brain metastasis are ruled out by a CT scan or MRI.
5. Major surgery within three weeks prior to study enrollment or not fully recovered from side effects of previous procedures.
6. Previous (less than 3 years ago) or current malignancies at sites other than curatively treated in situ carcinoma of the cervix of the uterus, or basal or squamous cell carcinoma of the skin.
7. Uncontrolled diabetes (defined as a Hgb A1C level >8%).
8. Significant active cardiac disease including: uncontrolled high blood pressure (ie, systolic blood pressure >180 mm Hg, diastolic blood pressure >95 mm Hg), unstable angina, deep venous thrombosis, pulmonary embolism, cerebro-vascular attack,
valvular disease, congestive heart failure, myocardial infarction within the previous 6 months, or serious cardiac arrhythmias.
9. Other serious uncontrolled medical disorder or active infection that would impair the ability to receive study treatment as determined by the investigator.
10. Subjects who are receiving chronic high dose systemic immunosuppressive steroid therapy (≥100 mg prednisone per day or >40 mg dexamethasone per day) within 2 weeks prior to enrollment. Previous moderate to high dose steroid treatment is allowed but must be stopped at enrollment. Topical steroid use, inhaled steroids, and low dose steroid use at time of randomization (eg, cortisone 30 mg/day, prednisone 5 mg/day) will be allowed.
11. Dementia or significantly altered mental status that would limit the understanding or rendering of informed consent and compliance with the requirements of this protocol.
12. Pregnancy or breast feeding.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Primary Endpoint: Overall Survival |
|
| 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) | 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 | 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 | Yes |
| E.8.2.3.1 | Comparator description |
| Study group not treated with test IMP only Erlotinib |
|
| 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 | 64 |
| 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 | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 5 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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