A Prospective Phase II, Randomized Multi-center Trial of a Combined Modularized Treatment With Metronomic Low-dose Treosulfan, Pioglitazone and Clarithromycin Versus Nivolumab in Patients With Squamous Cell Lung Cancer and Non- Squamous Cell Lung Cancer, Respectively After Platin Failure
Overview
- Phase
- Phase 2
- Intervention
- Pioglitazone
- Conditions
- Squamous Cell Lung Cancer
- Sponsor
- University Hospital Regensburg
- Enrollment
- 86
- Locations
- 9
- Primary Endpoint
- Progression Free Survival
- Last Updated
- 8 years ago
Overview
Brief Summary
This is a Phase II, multicentre, open-label, randomized, and controlled study, evaluating the efficacy and safety of combined modularized treatment of treosulfan, pioglitazone and clarithromycin in patients with with squamous and non- squamous cell lung cancer, respectively after platin failure.
Detailed Description
Patients will be randomized 1:1, and will be stratified according to histology (squamous cell carcinoma vs adenocarcinoma). 86 patients with platin refractory Non-Small Cell Lung Cancer (NSCLC) will be treated either with metronomic low-dose treosulfan, pioglitazone and clarithromycin (experimental arm) or with nivolumab (squamous cell lung cancer and nonsquamous cell lung cancer). Patients will undergo tumor assessments at baseline and every 6 weeks (approximately every two cycles) thereafter, until progression. Patients without progression after 36 weeks will undergo tumor assessments every 12 weeks.
Investigators
Albrecht Reichle
Prof. Dr.
University Hospital Regensburg
Eligibility Criteria
Inclusion Criteria
- •Signed Informed Consent Form
- •Ability to comply with protocol
- •Age ≥ 18 years
- •Measurable disease, as defined by RECIST v1.1
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Life expectancy ≥ 12 weeks
- •Histologically or cytologically confirmed 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);
- •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
- •No more than 2 cytotoxic chemotherapy regimens
- •Patients that have progressed during or after treatment with EGFR Tyrosine Kinase Inhibitor (TKI) in first line, or are intolerant to treatment with erlotinib, gefitinib, or another EGFR TKI may be included.
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. Radiographic demonstration of improvement upon the completion of CNS directed therapy and no evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study
- •History of intracranial hemorrhage
- •Ongoing requirement for dexamethasone for CNS disease
- •Stereotactic radiation or whole-brain radiation within 28 days prior to Cycle 1,Day 1
- •Screening CNS imaging ≥ 4 weeks since completion of radiotherapy and ≥ 2 weeks since discontinuation of corticosteroids
- •Spinal cord compression not definitively treated with surgery and/or radiation or previously diagnosed and treated spinal cord compression that has not been clinically stable for ≥ 2 weeks prior to randomization
- •Leptomeningeal disease
- •Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
- •Uncontrolled tumor-related pain: patients requiring pain medication must be on a stable regimen at study entry. Symptomatic lesions amenable to palliative radiotherapy should be treated prior to enrolment. Asymptomatic metastatic lesions whose further growth would likely cause functional deficits or intractable pain should be considered for loco-regional therapy prior to enrolment.
Arms & Interventions
A: Biomodulatory treatment
treosulfan 250 mg p.o. twice daily, pioglitazone 45 mg p.o. once daily, clarithromycin 250 mg p.o. twice daily until progression or no clinical benefit observed, whichever comes first.
Intervention: Pioglitazone
A: Biomodulatory treatment
treosulfan 250 mg p.o. twice daily, pioglitazone 45 mg p.o. once daily, clarithromycin 250 mg p.o. twice daily until progression or no clinical benefit observed, whichever comes first.
Intervention: Treosulfan
A: Biomodulatory treatment
treosulfan 250 mg p.o. twice daily, pioglitazone 45 mg p.o. once daily, clarithromycin 250 mg p.o. twice daily until progression or no clinical benefit observed, whichever comes first.
Intervention: Clarithromycin
B: Standard Treatment
Nivolumab, 3 mg per kilogram of body weight every 2 weeks until disease progression according to RECIST 1.1 or unacceptable toxicity
Intervention: nivolumab
Outcomes
Primary Outcomes
Progression Free Survival
Time Frame: up to 6 months after study completion
Secondary Outcomes
- Number of participants experiencing a change in cellular secretome analytics in serum(at screening, at the beginning of each new treatment cycle (each cycle consists of 28 days) and at the end of treatment visit, which will take place within 3 weeks of the last intake of study drug)
- Overall Survival(up to 6 months after study completion)
- Duration of Response(up to 6 months after study completion)
- Number of participants experiencing adverse events related to the study drugs(up to 6 months after study completion)
- proportion of patients who report a considerable degree of impairment in a respective dimension, i.e. a score value <50(up to 6 months after study completion)
- description of change in predictive and prognostic exploratory biomarkers for each participant(at screening,at the beginning of each treatment cycle (each treatment cycle consists of 28 days), and at the end of treatment visit, which will take place within 3 weeks of the last intake of study drug)
- Comparison of participants tumour response according to (Response Evaluation Criteria in Solid Tumors) RECIST criteria version 1.1 and Peroxisome proliferator-activated receptor gamma (PPAR-γ) expression(Baseline)