locally advanced or metastatic NSCLC, who have progressed during or following a platinum-containing regimen. MedDRA version: 20.0 Level: PT Classification code 10029522 Term: Non-small cell lung cancer stage IV System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classification code 10029521
Conditions
Interventions
Trade Name: Actos
Product Name: Pioglitazone
Pharmaceutical Form: Tablet
INN or Proposed INN: pioglitazone hydrochloride
Other descripti
Sponsors
Freistaat Bayer respresented by University of Regensburg represented by Kaufmännischer Direktor
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Signed Informed Consent Form • Ability to comply with protocol • Age = 18 years • Measurable disease, as defined by RECIST v1.1 • ECOG performance status of 0 or 1 • Life expectancy = 12 weeks • Histologically or cytologically documented locally advanced or metastatic (i.e., Stage IIIB not eligible for definitive chemoradiotherapy, Stage IV, or recurrent) NSCLC (per the Union Internationale Contre le Cancer/American Joint Committee on Cancer [UICC/AJCC] staging system); pathological characterization must be sufficient to define patients as having either squamous or non-squamous histology. o Patients who do not have tissue specimens meeting eligibility requirements may undergo a biopsy during the screening period. o Acceptable samples include core needle biopsies for deep tumor tissue (minimum 3 cores) or excisional, incisional, punch, or forceps biopsies for cutaneous, subcutaneous, or mucosal lesions. • Disease progression during or following treatment with a prior platinum-containing regimen for locally advanced, unresectable/inoperable or metastatic NSCLC or disease recurrence within 6 months of treatment with a platinum-based adjuvant/neoadjuvant regimen • a maximum of two prior cytotoxic chemotherapy regimens • Patients with an EGFR mutation treated with EGFR TKI in first-line must have progressed during or after treatment or be intolerant to erlotinib, gefitinib, or another EGFR TKI. • Patients with an ALK fusion oncogene must have progressed during or after treatment with, or be intolerant to, crizotinib or another ALK inhibitor. • The last dose of prior systemic anti-cancer therapy must have been administered = 21 days prior to randomization (= 14 days for vinorelbine or other vinca alkaloids or gemcitabine . • The last dose of treatment with any investigational agent or participation in a clinical trial with therapeutic intent must have ended = 28 days prior to randomization. • Prior radiation therapy is allowed provided the patient has recovered from any toxic effects thereof and = 7 days have elapsed between the last fraction and randomization. • Adequate hematologic and end organ function, defined by the following laboratory results obtained within 14 days prior to first study treatment: ANC = 1500 cells/µL (without granulocyte colony-stimulating factor support within 2 weeks of test), WBC counts > 2,500/µL and 2.5 × ULN; Serum bilirubin = 1.0 × ULN. Patients with known Gilbert’s disease who have serum bilirubin level = 3 × ULN are eligible. • INR and aPTT = 1.5 × ULN (only for patients not receiving therapeutic anticoagulation). Patients receiving therapeutic anticoagulation must be on a stable dose for at least 1 week prior to randomization. • Female patients of childbearing potential and male patients with partner
Exclusion criteria
Exclusion criteria: Cancer-Specific Exclusion criteria • Known active or untreated central nervous system (CNS) metastases • Patients with a history of treated asymptomatic CNS metastases are eligible, if they meet all of the following criteria: No metastases to brain stem, midbrain, pons, medulla, cerebellum, or within 10 mm of the optic apparatus (optic nerves and chiasm). Radiographic demonstration of improvement after CNS directed therapy and no evidence of interim progression between the completion of CNS-directed therapy and CNS screening imaging.Screening CNS radiographic imaging = 4 weeks since completion of radiotherapy and = 2 weeks since discontinuation of corticosteroids • History of intracranial hemorrhage • Completed stereotactic radiation or whole-brain radiation within 28 days prior to Cycle 1, Day 1 • Spinal cord compression not definitively treated with surgery and/or radiation, or previously treated spinal cord compression that has been clinically stable for less than 2 weeks prior to randomization • Leptomeningeal disease • Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage • Uncontrolled tumor-related pain: Patients requiring pain medication must be on a stable regimen at study entry. Symptomatic lesions amenable to palliative radiotherapy (e.g., bone metastases or metastases causing nerve impingement) should be treated prior to enrolment. • Uncontrolled hypercalcemia (> 1.5 mmol/L ionized calcium or Ca > 12 mg/dL or corrected serum calcium > ULN) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab • Malignancies other than NSCLC within 5 years prior to randomization, with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated surgically with curative intent, ductal carcinoma in situ treated surgically with curative intent). General Exclusion criteria • History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis • Serum albumin < 2.5 g/dL • Patients with active hepatitis B or hepatitis C. Patients positive for HCV antibody are eligible only if PCR is negative for HCV RNA. • Significant uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results, including significant liver disease (such as cirrhosis, uncontrolled major seizure disorder, or superior vena cava syndrome) • Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within 3 months prior to randomization, unstable arrhythmias, or unstable angina. • Patients with a known left ventricular ejection fraction (LVEF) < 40%. Patients with known coronary artery disease, congestive heart failure not meeting the above criteria, or LVEF < 50% must be on a stable medical. • Active or latent tuberculosis • Severe infections within 4 weeks prior to randomization, including hospitalizat
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy of a biomodulatory therapy with treosulfan, pioglitazone and clarithromycin compared to nivolumab in NSCLC (squamous and non-squamous cell lung cancer) as measured by progression-free survival (PFS); Secondary Objective: •evaluate the efficacy of the combined biomodulatory treatment with treosulfan, pioglitazone and clarithromycin compared to nivolumab measured by •overall survival •duration of response per RECIST v1.1 •evaluate the safety and tolerability of the treatment with treosulfan, pioglitazone and clarithomycin compared to nivolumab •evaluate universal response parameters (cellular secretome analytics in serum) for modulation of hallmarks of cancer •To evaluate and compare patient reported outcomes of lung cancer symptoms, patient functioning, and health-related quality of life between treatment arms, using EORTC, QLQ-C30 and LC13 •evaluate the relationship between tumor tissue PPAR? expression and efficacy •assess change in predictive and prognostic exploratory biomarkers in archival and/or fresh serum samples •Tumor tissue taken at diagnosis or relapse: Routine moleculargenetic biomarkers and tissue microarray for PPARgamma expression ;Primary end point(s): progression-free survival (PFS);Timepoint(s) of evaluation of this end point: the analysis is event driven and will be done when 69 events have occured. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • To evaluate the efficacy of the combined modularized treatment with treosulfan, pioglitazone and clarithromycin compared to nivolumab o overall survival (OS) o duration of response (DOR) per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) • To evaluate the safety and tolerability of the treatment with treosulfan, pioglitazone and clarithomycin compared to nivolumab. • To evaluate universal response parameters (cellular secretome analytics in serum) for modulation of hallmarks of cancer (inflammation, angiogenesis and immune response). To evaluate and compare patient reported outcomes (PROs) of lung cancer symptoms, patient functioning, and health-related quality of life (HRQoL) between treatment arms, using the European Organisation for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire Core 30 (QLQ-C30) and its Lung Cancer Module (LC13) • To evaluate the relationship between tumor tissue PPAR? expression and efficacy • To assess change in predictive and prognostic exploratory biomarkers on fresh serum samples | — |
Countries
Germany
Contacts
Public ContactProf. A. Reichle
Universitätsklinikum Regensburg
Outcome results
None listed