A Trial With Metronomic Low-dose Treosulfan, Pioglitazone and Clarithromycin Versus Standard Treatment in NSCLC

NCT02852083 | Unknown Phase 2

• 1 other identifier: ModuLung
• Study Type: interventional
• Target: 86
• Locations: 1 country
• Sites: 9

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.

Conditions

Squamous Cell Lung Cancer; Non-Squamous Cell Lung Cancer; Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival

  up to 6 months after study completion

Secondary Outcomes (8)

• 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

• 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

• 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

Study Arms (2)

A: Biomodulatory treatment

EXPERIMENTAL

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.

Drug: Pioglitazone; Drug: Treosulfan; Drug: Clarithromycin

B: Standard Treatment

ACTIVE COMPARATOR

Nivolumab, 3 mg per kilogram of body weight every 2 weeks until disease progression according to RECIST 1.1 or unacceptable toxicity

Drug: nivolumab

Interventions

Pioglitazone DRUG

Pioglitazone 25 mg once daily, p.o.

Also known as: Actos

A: Biomodulatory treatment

nivolumab DRUG

3 mg per kilogram of body weight every 2 weeks, p.o. (standard treatment)

Also known as: Opdivo

B: Standard Treatment

Treosulfan DRUG

Treosulfan 250 mg twice daily, p.o.

A: Biomodulatory treatment

Clarithromycin DRUG

Clarithromycin 250 mg twice daily p.o.

A: Biomodulatory treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Patients that have progressed during or after , or intolerant to treatment with 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 must have ended ≥ 28 days prior to randomization.
• Prior radiation therapy is allowed provided recovery from any toxic effects thereof and ≥ 7 days between the last fraction and randomization.
• Adequate hematologic and end organ function, defined by the following (max 14 days prior study treatment): Absolute Neutrophil Count (ANC) ≥ 1500 cells/μL (without granulocyte colonystimulating factor support within 2 weeks of sampling), White Blood Cell (WBC) counts \> 2,500/μL and \< 15,000/μL, lymphocyte count ≥ 500/μL, Platelet count ≥ 100,000/μL (without transfusion within 2 weeks of sampling), Hemoglobin ≥ 9.0 g/dL. Transfusion or erythropoietic treatment is allowed.

You may not qualify if:

• 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.
• Hypercalcemia (Ca \> 1.5 mmol/L ionized calcium or Ca \> 12 mg/dL or corrected serum calcium \> ULN) or symptomatic hypercalcemia requiring continuous bisphosphonate therapy or denosumab. Patients who are receiving bisphosphonate therapy or denosumab specifically to prevent skeletal events and without a history of clinically significant hypercalcemia are eligible.
• 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 curative outcome
• History of idiopathic pulmonary fibrosis (including pneumonitis), history of drug-induced pneumonitis
• Serum albumin \< 2.5 g/dL
• Patients with active hepatitis B or hepatitis C. Patients with past Hepatitis B Virus (HBV) infection or resolved HBV are eligible. Patients positive for Hepatitis C Virus (HCV) antibody are eligible only if Polymerase Chain Reaction (PCR) is negative for HCV Ribonucleic Acid (RNA).
• Significant uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results, including significant liver disease

Sponsors & Collaborators

• University Hospital Regensburg: lead
• The Anticancer Fund: collaborator

Study Sites (9)

Onkologische Gemeinschaftspraxis Dres. Wilke/ Wagner/Petzoldt

Fürth, Bavaria, Germany

RECRUITING

Klinikum Kempten Oberallgäu

Immenstadt im Allgäu, Bavaria, Germany

RECRUITING

MVZ am Klinikum GmbH

Passau, Bavaria, Germany

RECRUITING

Universitätsklinikum Regensburg

Regensburg, Bavaria, Germany

RECRUITING

Kliniken Nordoberpfalz AG, Klinikum

Weiden, Bavaria, Germany

RECRUITING

MVZ Weiden GmbH

Weiden, Bavaria, Germany

RECRUITING

St. Antonius-Hospital

Eschweiler, North Rhine-Westphalia, Germany

RECRUITING

Klinik für Innere Medizin

Homburg/Saar, Saarland, Germany

RECRUITING

Krankenhaus Martha-Maria

Halle, Saxony-Anhalt, Germany

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Pioglitazone; Nivolumab; treosulfan; Clarithromycin

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Erythromycin; Macrolides; Polyketides; Lactones

Central Study Contacts

Albrecht Reichle, MD

CONTACT

albrecht.reichle@klinik.uni-regensburg.de

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr.

Study Record Dates

• First Submitted: July 12, 2016
• First Posted: August 2, 2016
• Study Start: January 1, 2016
• Primary Completion: July 1, 2019
• Study Completion: July 1, 2020
• Last Updated: January 18, 2018

Record last verified: 2018-01

Locations

DE (9)