| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Advanced 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 | PT |
| E.1.2 | Classification code | 10059515 |
| E.1.2 | Term | Non-small cell lung cancer metastatic |
|
| 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 |
|
| 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.1.2 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 |
|
| 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 assess the efficacy of AG-013736 in combination with cisplatin/gemcitabine in
patients with advanced/metastatic, squamous NSCLC. |
|
| E.2.2 | Secondary objectives of the trial |
• To assess the safety of AG-013736 in combination with cisplatin/gemcitabine in
patients with squamous NSCLC
• To assess population pharmacokinetics for AG-013736
• To explore VEGF receptor signaling in circulating endothelial cells in this patient
population |
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Title: MOLECULAR PROFILING SUPPLEMENT SAMPLES FOR PFIZER’S EXPLORATORY RESEARCH BIOBANK
Date: 4 March 2008
Version: Final
The primary objective of this additional research component is to collect, store, and use samples to investigate possible associations between genomic and metabonomic variation:
• in relation to response to the study drugs, and
• in relation to characteristics of the disease/condition under study in the associated clinical trial, and related conditions.
In addition, samples may be used as controls in genomic and metabonomic investigations of the causes, natural history, and other aspects of important diseases and conditions for which Pfizer is researching new or improved drug therapies.
Scientific information about these differences among groups of subjects can help researchers to better understand the response of subjects to investigational drugs and to learn more about diseases/conditions for which we are developing treatments.
Samples collected will be stored in Pfizer’s Exploratory Research Biobank in the USA. |
|
| E.3 | Principal inclusion criteria |
1. Histologically- or cytologically-confirmed diagnosis of squamous NSCLC
• Cytologic specimens for diagnosis must have been obtained from bronchial brushings or washings or from needle aspiration of a defined lesion. Sputum cytology alone will not be sufficient for diagnosis.
• Patients with mixed NSCLC histology should be classified by the predominant
histologic type.
2. Stage IIIB with malignant effusion (fluid cytology demonstrating malignant cells
required), Stage IV, or recurrent disease after definitive local therapy
3. Candidate for primary treatment with cisplatin and gemcitabine
4. Presence of measurable disease by RECIST
5. Adequate organ function as defined by the following criteria:
a. Absolute neutrophil count (ANC) ≥1500 cells/mm3
b. Platelet count ≥100,000 cells/mm3
c. Hemoglobin ≥9 g/dL
d. AST and ALT =<2.5 x ULN, or AST and ALT =<5 x ULN if liver function
abnormalities are due to underlying malignancy
e. Total bilirubin ≤1.5 x ULN
f. Calculated creatinine clearance or measured creatinine clearance ≥60 mL/min.
g. Urine protein < 1+ by dipstick. If dipstick is ≥ 1+ then urine protein:creatinine ratio
must be < 1 to be eligible.
6. Age ≥18 years
7. Life expectancy >12 weeks
8. ECOG performance status of 0 or 1
9. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures
10. Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the trial before enrollment |
|
| E.4 | Principal exclusion criteria |
1. Prior systemic treatment for Stage IIIB (with malignant effusion) or Stage IV NSCLC. Adjuvant chemotherapy or chemoradiation (sequential or concomitant) is permitted if the last dose of systemic therapy was ≥12 months prior to start of study treatment
2. Prior treatment with a VEGF or VEGFR inhibitor
3. Radiation therapy within 21 days, major surgery within 28 days, or minor procedures including fine needle aspiration within 7 days of study treatment. All acute toxicities must have resolved to baseline or to CTC Grade 1 (NCI CTCAE v3.0).
4. One or more lung lesions with cavitation, or any lesion invading or abutting a major blood vessel as assessed by CT or MRI.
5. History of hemoptysis > ½ tsp (2.5 ml) of blood per day for a day or more within 1 week of study treatment, or Grade 3 or 4 hemoptysis within 4 weeks of study treatment
6. NCI CTCAE Grade 3 hemorrhage from any cause within 4 weeks of study treatment
7. Preexisting uncontrolled hypertension as documented by 2 baseline blood pressure readings taken at least 1 hour apart. The baseline systolic blood pressure readings must be ≤140 mm Hg, and the baseline diastolic blood pressure readings must be ≤90 mm Hg. Patients whose hypertension is controlled by antihypertensive therapies are eligible
8. Untreated brain metastases. Patients with previously diagnosed CNS metastases are eligible if they have completed radiation therapy to the brain at least 4 weeks prior to study treatment, have recovered from the acute effects of that treatment, have discontinued corticosteroid treatment for at least 2 weeks prior to study treatment, and are eurologically stable
9. Seizure ≤ 28 days or use of an anticonvulsant ≤14 days prior to study treatment.
10. History of a bleeding diathesis or coagulopathy ≤ 12 months of study entry
11. Need for therapeutic anticoagulation, regular use of aspirin (> 325 mg/day), NSAID or other medications known to inhibit platelet function. (Low-dose anticoagulants, such as low-dose heparin or ≤2 mg/day of warfarin for prevention of deep venous thrombosis or maintenance of patency of central venous access devices is permitted).
12. Any of the following ≤ 12 months prior to study treatment: myocardial infarction,
severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, deep vein thrombosis or pulmonary embolism
13. Gastrointestinal abnormalities including inability to take oral medication, requirement for intravenous alimentation, prior total gastric resection, treatment for endoscopy confirmed active peptic ulcer disease within 6 months prior to study treatment, active gastrointestinal bleeding (as evidenced by hematemesis, hematochezia or melena) within 3 months of study treatment, or malabsorption syndromes
14. Positive serum or urine pregnancy test within 7 days of study treatment. (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.)
15. Female patients who are breastfeeding
16.Active malignancies except for NSCLC
17. Neuropathy (Grade ≥ 2 CTCAE Version 3.0) or known high frequency range hearing impairment
18. Known hypersensitivity to gemcitabine or one of its inactive ingredients or to cisplatin or other platinum compounds, or any other known or suspected contraindications to receive treatment with gemcitabine and cisplatin
19. Current use or anticipated need for treatment with drugs that are known potent CYP3A4 inhibitors (e.g. verapamil, ketoconazole, itraconazole, erythromycin, clarithromycin, indinavir, saquinavir, ritonavir, nelfinavir, lopinavir, and delavirdine). For the same reason grapefruit juice must be avoided during the study.
20. Current use or anticipated need for treatment with drugs that are known CYP3A4 or CYP1A2 inducers (i.e., carbamazepine, dexamethasone, felbamate, omeprazole, phenobarbital, phenytoin, primidone, rifabutin, rifampin, and St. John’s wort). (Note: The use of dexamethasone as a premedication for chemotherapy is not an exclusion criterion)
21. Participation in other interventional studies within 28 days before or during dosing in the current study
22. 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 |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
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. |
|
| 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 | Information not present in EudraCT |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| 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 | No |
| E.8.1.1 | Randomised | Information not present in EudraCT |
| E.8.1.2 | Open | Information not present in EudraCT |
| E.8.1.3 | Single blind | Information not present in EudraCT |
| E.8.1.4 | Double blind | Information not present in EudraCT |
| E.8.1.5 | Parallel group | Information not present in EudraCT |
| E.8.1.6 | Cross over | Information not present in EudraCT |
| E.8.1.7 | Other | Information not present in EudraCT |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
| E.8.2.2 | Placebo | Information not present in EudraCT |
| E.8.2.3 | Other | Information not present in EudraCT |
| 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 | 2 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 10 |
| 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 | No |
| 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
|
| Definition provided in Section 13.2 of protocol |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| 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 | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
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