| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| First line treatment of chemotherapy-naive patients with locally advanced (Stage IIIB with pleural effusion) or metastatic (Stage IV) Non Small Cell Lung Cancer (NSCLC) |
|
| MedDRA Classification |
| 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 overall survival (OS) in patients randomized to paclitaxel/carboplatin + PF-3512676 (Investigational Treatment Arm) versus that in patients randomized to paclitaxel/carboplatin alone (Control Treatment Arm) |
|
| E.2.2 | Secondary objectives of the trial |
- To compare additional measures of efficacy, safety and health-related quality of life and disease/treatment-related symptoms in patients randomized to paclitaxel/carboplatin + PF-3512676 versus patients randomized to paclitaxel/carboplatin alone
- To evaluate the effect of PF-3512676 on the pharmacokinetics of paclitaxel and carboplatin
- To evaluate the pharmacokinetics of PF-3512676 when administered in combination with paclitaxel/carboplatin
|
|
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
1. Histologically or cytologically confirmed diagnosis of non-small cell lung cancer (NSCLC)
Cytologic specimens for diagnosis or for cell type classification must have been obtained from bronchial brushings or washings or from needle aspiration of a defined lesion. Sputum cytology alone will not be acceptable for diagnosis or for cell type classification.
2. Advanced NSCLC with documented AJCC Stage IIIB (with pleural effusion) or Stage IV disease.
3. Measurable disease defined by at least one lesion that can be accurately measured in at least one dimension as >=20 mm with conventional techniques or >=10 mm with spiral CT scan within 28 days prior to the planned start of study treatment (RECIST criteria). Note: Prior radiation to the only site of measurable disease will deem the patient ineligible unless progression is documented at the site after completion of radiation.
4. No prior systemic treatment for NSCLC with chemotherapy, immunotherapy, biologic response modifiers or other investigational drugs.
5. Prior surgery or radiation therapy is permitted if completed at least 3 weeks prior to enrollment and all acute toxicities have resolved to baseline or to CTC Grade 1 (NCI CTCAE v3.0)
6. Males or females aged >=18 years
7. ECOG performance status (PS) 0 or 1
8. Adequate organ function as determine by the following criteria:
- Absolute neutrophil count (ANC) >=1.5 x 10 000 000 000/L.
- Platelet count >=100 x 10 000 000 000/L
- Serum creatinine =<1.5 x upper limit of normal (ULN)
- AST (SGOT) and ALT (SGPT) =<5 x ULN
- Total bilirubin =<1.25 x ULN
9. 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 3 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 3 months thereafter. The definition of effective contraception will be based on the judgment of the principal investigator or a designated associate.
10. Written, voluntary informed consent provided
|
|
| E.4 | Principal exclusion criteria |
1. Any histological/cytological evidence of small cell or carcinoid lung cancer.
2. Known central nervous system (CNS) metastasis.
CNS imaging is not required at baseline for patients who have no symptoms suggestive of CNS metastases
3. Any 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:
- Pre-existing autoimmune or antibody-mediated diseases including but not limited to: systemic lupus, erythematosis, rheumatoid arthritis, multiple sclerosis, Sjogren’s syndrome, autoimmune thrombocytopenia, or glomerulonephritis.
- History of allogeneic transplant
- Untreated or uncontrolled superior vena cava syndrome
- Untreated or uncontrolled hypercalcemia
- Requirement for chronic treatment with therapeutic doses of systemic corticosteroids. Use of steroid inhalers, or oral “physiologic replacement” doses of corticosteroids is permitted. Physiological replacement doses will be defined as =<37.5 mg/day of cortisone, =<7.5 mg/day of prednisolone or =<1.0 mg/day of dexamethasone. Patients on other replacement regimens must be discussed with the sponsor.
- Uncontrolled hypertension, unstable angina, myocardial infarction or symptomatic congestive heart failure within the past 12 months or serious uncontrolled cardiac arrhythmia.
- 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.
- Pre-existing peripheral neuropathy >= CTC Grade 2.
- 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. History of any active malignancy (other than NSCLC) during the last 3 years except non melanoma skin cancer, in situ cervical cancer, or cured, early prostate cancer in a patient with PSA level < ULN.
5. Known or suspected hypersensitivity to any of the study drugs (paclitaxel, carboplatin or PF-3512676), study drug classes (taxane, platinum, oligodeoxynucleotide ODN) or excipients in the formulation of study drugs (including castor oil and derivatives such as Cremophor®)
6. Female patients who are pregnant or nursing.
7. Inability or lack of willingness to comply with scheduled visits, therapy plans or laboratory tests.
8. Current enrollment in another therapeutic clinical trial.
9. Use of any investigational agent in the past 4 weeks. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Primary Endpoint:
- Overall survival defined as the time from randomization to the date of death due to any cause.
Secondary Endpoints:
- Overall confirmed objective response rate (ORR), defined as the proportion of patients with a confirmed best response characterized as either a complete response (CR) or partial response (PR) (target lesions and tumor response defined according to RECIST guidelines). Confirmed responses are those that persist on a follow-up imaging assessment >=4 weeks after the initial objective documentation of response.
- Duration of response (DR) defined as the time from first documentation of response to the date of progression.
- Progression Free Survival (PFS) defined as the time from randomization to the date of progression or death due any cause, whichever occurs first.
- Time to tumor progression (TTP) defined as the time from randomization to the date of progression.
- Overall safety profile characterized by type, frequency, severity (as graded using NCI (National Cancer Institute) Common Terminology Criteria for Adverse Events (CTCAE), v3.0 and relationship to study therapy of adverse events and laboratory abnormalities.
- Patient Reported Outcome (PRO) changes in scores for health-related quality of life and disease/treatment-related symptoms according to EORTC QLQ-C30 and QLQ-LC-13
- Pharmacokinetic parameters to include but not necessarily limited to Cmax and AUC for paclitaxel, carboplatin, and PF-3512676. |
|
| 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 | Information not present in EudraCT |
| 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 | 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 | Yes |
| E.8.2.3.1 | Comparator description |
| paclitaxel/carboplatin chemotherapy alone |
|
| 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.8.5 | The trial involves multiple Member States | Yes |
| 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 | Information not present in EudraCT |
| 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
|
End of Trial is defined as the time at which:
- Enrollment is completed according to protocol planned sample size, and assessments and requirements are completed as per protocol.
- The stated objectives of the trial are achieved (including results of interim analysis or DSMC review/recommendations if they lead to an anticipated closure).
A Final Study Visit will occur for all patients when disease progression is documented or subsequent anticancer therapy is initiated. |
|
| 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 | 6 |
| 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 | 6 |
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