Stage IIIB and IV Bronchioloalveolar Carcinoma and Adenocarcinoma with Bronchioloalveolar Features
Conditions
Interventions
Product Name: VELCADE 3.5 mg powder for solution for injection
Product Code: PS-341, 26866138-AAA-PB-001
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: bortezomib
CAS Numbe
Sponsors
Janssen Cilag International, N.V. (Sponsor in European Union)
Eligibility
Sex/Gender
All
Inclusion criteria
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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
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 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 pi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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).;Secondary Objective: - 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.;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. | — |
Countries
Germany, Italy
Outcome results
None listed