| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Patients who have a histologically or cytologically documented diagnosis of nonsquamous stage IIIB or stage IV NSCLC that is not amenable to curative therapy. |
|
| 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 | 10025054 |
| E.1.2 | Term | Lung cancer non-small cell stage IIIB |
|
| 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 |
| The primary objective of this Phase 2 study is to assess the efficacy of pemetrexed-cisplatin combined with bevacizumab as induction therapy and pemetrexed-bevacizumab as maintenance therapy in the first-line treatment of patients with Stage IIIB or IV nonsquamous NSCLC, as measured by PFS. |
|
| E.2.2 | Secondary objectives of the trial |
•Overall survival (OS)
•Overall response rate (ORR)
•Safety and tolerability
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
[1] Histological or cytological diagnosis of nonsquamous Stage IIIB or Stage IV NSCLC that is not amenable to curative therapy. See Protocol Attachment S125.2, American Joint Committee on Cancer Staging Criteria for Lung Cancer; Greene et al. 2002.
[2] ECOG PS of 0 or 1 (Oken et al. 1982) (see Protocol Attachment S125.3).
[3] Patients with prior radiation therapy may be eligible for this study if
they meet the following guidelines:
• Previous radiation therapy is allowed if it was to <25% of the bone marrow (Cristy and Eckerman 1987), but should have been limited and must not have included whole pelvis radiation.
• Patients must have recovered from the toxic effects of the treatment prior to study enrollment (except for alopecia).
• Prior thoracic radiotherapy must be completed 30 days before study enrollment.
• Lesions that have been radiated cannot be included as sites of measurable disease unless clear tumor progression has been documented in these lesions since the end of radiation therapy.
• Palliative extrathoracic radiotherapy to preexisting lesions may continue on study; however, these lesions may not be included as sites of measurable disease.
[4] At least 1 unidimensionally measurable lesion meeting RECIST criteria (at least 10 mm in longest diameter [LD] by spiral computed tomography [CT] scan, or at least 20 mm by standard techniques) (see Protocol Attachment S125.4, Therasse et al. 2000). Positron emission tomography (PET) scans and ultrasounds may not be used for tumor measurements.
[5] Estimated life expectancy of at least 12 weeks.
[6] Patient compliance and geographic proximity that allow adequate follow up.
[7] Adequate organ function, including the following:
• Adequate bone marrow reserve: absolute neutrophil (segmented and bands) count (ANC) 1.5 109/L, platelets 100 109/L, and hemoglobin 10 g/dL.
• Hepatic: bilirubin 1.5 times the upper limit of normal ( ULN); alkaline phosphatase (AP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) 3.0 ULN (AP, AST, and ALT 5 ULN is acceptable if liver has tumor involvement).
• Renal: calculated creatinine clearance (CrCl) mL/min based on the original weight-based Cockroft and Gault formula (see Protocol Attachment S125.5; Cockcroft and Gault 1976), and serum creatinine 1.5 ULN.
At the time of enrollment, if the urinalysis dipstick result is 2+ for protein, a 24-hour urine collection should be taken. In these cases, patients must have 1g protein/24 hours to be eligible for study participation.
[8] For women: Must be surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy), postmenopausal, or compliant with a medically approved contraceptive regimen (for example, intrauterine device, birth control pills, or barrier device) during and for 6 months after the treatment period; must have a negative serum or urine pregnancy test within 7 days before study enrollment; and must not be breastfeeding.
For men: Must be surgically sterile or compliant with a contraceptive regimen during and for 6 months after the treatment period.
[9] Patients must sign an ICD.
[10] Patients must be at least 18 years of age.
|
|
| E.4 | Principal exclusion criteria |
[11] Have received prior systemic anticancer therapy for lung cancer (including adjuvant early-stage treatment for NSCLC).
[12] Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry.
[13] Have a serious concomitant systemic disorder (for example, active infection including human immunodeficiency virus) that, in the opinion of the investigator, would compromise the patient’s ability to adhere to the protocol.
[14] Have a serious cardiac condition, such as myocardial infarction within 6 months, angina, or heart disease, as defined by the New York Heart Association Class III or IV (see Protocol Attachment S125.6).
[15] Have had a prior malignancy other than NSCLC, carcinoma in situ of the cervix, or nonmelanoma skin cancer, unless that prior malignancy was diagnosed and definitively treated at least 5 years previously with no subsequent evidence of recurrence. Patients with a history of low-grade (Gleason score 6) localized prostate cancer will be eligible even if diagnosed less than 5 years previously.
[16] Have a second primary malignancy that is clinically detectable at the time of consideration for study enrollment.
[17] Have central nervous system (CNS) metastases. Brain imaging is required in symptomatic patients to rule out brain metastases, but is not required in asymptomatic patients.
[18] Are receiving concurrent administration of any other antitumor therapy.
[19] Are taking or have recently taken (within 10 days of enrollment) aspirin (>325 mg/d), clopidogrel at doses >75 mg/d, dipyramidole, ticlopidine, or cliostazol. Patients are also excluded if they cannot hold nonsteroidal anti-inflammatory agents, other than prophylactic therapy with low-dose aspirin, for a 5-day period during each cycle (8 day period for long-acting agents, such as piroxicam) (see Section 5.7.6 for details).
[20] Are unable or unwilling to take folic acid or vitamin B12 supplementation.
[21] Are unable or unwilling to take corticosteroids.
[22] Have a history of gastrointestinal fistula, perforation, or abscess, inflammatory bowel disease, or diverticulitis.
[23] Have clinically significant (by physical exam) third-space fluid collections, for example, ascites or pleural effusions that cannot be controlled by drainage or other procedures prior to study entry.
[24] Have had significant weight loss (that is, 10%) over the previous 6 weeks before study entry.
[25] Have a history of gross hemoptysis (bright red blood of ½ teaspoon per episode of coughing) <3 months prior to enrollment or history or evidence of inherited bleeding diathesis or coagulopathy with the risk of bleeding.
[26] Are taking or have recently taken (within 10 days of enrollment) full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic purposes. Prophylactic use of anticoagulants is allowed; international normalized ratio (INR) should be <1.5 at study enrollment.
[27] Have a history of hypertension, unless hypertension is well controlled upon study entry (150/90 mm Hg) and the patient is on a stable regimen of antihypertensive therapy. Patients should not have any prior history of hypertensive crisis or hypertensive encephalopathy.
[28] Have had major surgery, open biopsy, or significant traumatic injury within 28 days prior to study enrollment, or anticipate the need for major surgical procedure during the course of the study.
[29] Have a history of a serious reaction to a monoclonal antibody. Patients with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies are not eligible.
[30] Have received a recent (within 30 days of enrollment) or are receiving concurrent yellow fever vaccination.
[31] History of thrombotic disorders within the last 6 months prior to entry.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Progression free 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 | No |
| 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) | 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 | No |
| 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) | No |
| 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 | 2 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 22 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| 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
| |
| 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 | 7 |
| 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 | 7 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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