E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Stage IIIB and IV Bronchioloalveolar Carcinoma and Adenocarcinoma with Bronchioloalveolar Features |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this study is to determine the efficacy of VELCADE in terms of tumor response rate [Complete Response (CR) and Partial Response (PR)] using the Response Evaluation Criteria In Solid Tumors (RECIST) guidelines in patients with advanced bronchioloalveolar carcinoma (BAC) or adenocarcinoma with BAC features that have progressed on or after Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors (EGFR TKI). |
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E.2.2 | Secondary objectives of the trial |
- Determine the duration of response, disease control rate, time to progression (TTP), and survival following VELCADE therapy. - Assess the toxicity and tolerability of VELCADE therapy. - Correlate somatic mutations in k-ras and EGFR genes with response to VELCADE therapy. - Explore the association between somatic mutations and expression levels in genes that may be involved in BAC prognosis or response to VELCADE therapy (p53, cyclin D1, Ki-67, p21cip1, p27kipl, thyroid transcription factor-1 (TTF-1), osteopontin, proteasome subunits). - Assess patient reported outcomes (PROs) using quality of life (QOL) instruments [EORTC-QLQ-C30 with its lung cancer module QLQ-LC13, and the Lung Cancer Symptom Scale (LCSS)]. - Assess the medical resource utilization (MRU) related to the disease and the therapy. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Have histologically confirmed BAC or adenocarcinoma with BAC features. 2. Have stage IIIB (malignant pleural effusion) or stage IV disease. 3. Have disease that has progressed on or after treatment with an EGFR TKI (Iressa or Tarceva). 4. Have radiographic documentation of Progressive Disease (PD) as determined by the investigator. 5. Have measurable disease by RECIST, defined as at least 1 lesion that can be accurately measured in at least 1 dimension as >20 mm with conventional tech- niques or >10 mm with spiral CT scan; the longest diameter is to be recorded. 6. Are 18 years of age or older. 7. Have a life expectancy greater than 3 months. 8. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2. 9. Are able to provide written informed consent in accordance with all applicable regulations and follow the study procedures. Patients must be capable of un- derstanding the investigational nature, potential risks and benefits of the study. |
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E.4 | Principal exclusion criteria |
1. Have a histological diagnosis of BAC or adenocarcinoma with BAC features based solely on the following sample types: · fine needle aspirate (FNA) · sputum cytology · bronchial brushings and washings cytology (bronchioalveolar lavage) · bronchial biopsy (bronchial wall only with no alveolar parenchyma, or mediastinoscopy with lymph node metastasis only). 2. Have had conventional cytotoxic chemotherapy within 3 weeks prior to en- rollment or treatment with an EGFR TKI within 2 weeks prior to enrollment. 3. Have peripheral neuropathy of Grade 2 or greater intensity, as defined by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE 3.0). 4. Have documented greater than 10% weight loss in the 6 weeks prior to enrollment. 5. Have been previously treated with VELCADE. 6. Have experienced myocardial infarction within 6 months prior to enrollment or have New York Hospital Association (NYHA) Class III or IV heart failure, un- controlled angina, electrocardiographic evidence of acute ischemia, or clinically significant and poorly controlled arrhythmias. 7. Have had radiation therapy within 4 weeks prior to enrollment. 8. Have had monoclonal antibody therapy within 4 weeks prior to enrollment. 9. Have had any major surgery within 4 weeks prior to enrollment 10. Have inadequate organ function at the Screening Visit as defined by the following laboratory values: - Platelet count <100 x 109/l - Hemoglobin <8.0 g/dl - Absolute neutrophil count (ANC) <1.5 x109/l - Aspartate transaminase (AST) >3 times the upper limit of the normal range (ULN) - Alanine transaminase (ALT) >3 times ULN - Creatinine >1.8 mg/dl - Total bilirubin >1.5 times ULN or >=5 times ULN in patients with liver metastases 11. Have brain metastases that have not been completely resected or have not completely responded to treatment with radiation therapy and there is evidence of residual disease; or that require ongoing treatment with corticosteroids. 12. Have uncontrolled active systemic infection requiring treatment 13. Have evidence of a co-existing advanced or metastatic malignancy other than BAC or adenocarcinoma with BAC features. 14. Have a history of allergic reaction attributable to compounds containing boron or mannitol. 15. Have known human immunodeficiency virus (HIV) positive or hepatitis B surface antigen-positive status or known active hepatitis C infection. Patients assessed by the investigator to be at risk for HIV, hepatitis B or C infection should be tested in accordance with local regulations. 16. Have poorly controlled hypertension, diabetes mellitus, or another serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol. 17. Are a pregnant or breast-feeding female. Confirmation that the patient is not pregnant must be established by a negative serum or urine beta-human chorionic gonadotropin (beta-hCG) pregnancy test result obtained during the Screening Period. Pregnancy testing is not required for post-menopausal or surgically sterilized women. 18. Are of childbearing potential and are unwilling to employ adequate means of contraception (condoms, diaphragm, birth control pills, injections, intrauterine device, or abstinence) during study treatment and through 30 days after the last dose of study treatment. 19. Are currently receiving or have previously received an investigational agent for any reason within 4 weeks of enrollment. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The study's primary endpoint is the efficacy of VELCADE therapy as measured by objective tumor response rate (CR and PR) in patients with locally advanced (stage IIIB) or metastatic (stage IV) BAC or adenocarcinoma with BAC features who have progressed following receipt of 1 or 2 prior lines of chemotherapy, which must have included an EGFR-TKI. |
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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 | No |
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) | 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 | No |
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.8.5 | 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 |
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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
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The end of the study is defined as 6 months following the last dose of the patient on study, at which time no further patient assessment will take place. This definition has been chosen in order to ensure that the time related endpoint objectives can be met. |
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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 | 2 |