Non-small-cell lung cancer previously treated MedDRA version: 14.1 Level: LLT Classification code 10025054 Term: Lung cancer non-small cell stage IIIB System Organ Class: 100000004864 MedDRA version: 14.1 Level: LLT Classification code 10025055 Term: Lung cancer non-small cell stage IV System Organ Class: 100000004864
Conditions
Interventions
Product Name: Picropodophyllin
Product Code: AXL1717
Pharmaceutical Form: Oral suspension
CAS Number: 477-47-4
Current Sponsor code: AXL1717
Other descriptive name: AXL1717(H2O), Picropodophyllin, BVT
Sponsors
Axelar AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Be informed of the nature of the study and have provided written informed consent 2. At least 18 years of age 3. Histologically confirmed diagnosis of locally advanced, or metastatic squamous cell carcinoma or adenocarcinoma histological subtypes of non-small-cell lung cancer (stage IIIB or IV) 4. For patients with squamous cell histology: previously treated with first-line chemotherapy and has had disease progression during or after first-line therapy. Patients with SCC who have received more than one line of chemotherapy for NSCLC are not eligible. 5. For patients with adenocarcinoma histology: previously treated with one or two lines of chemotherapy. Use of switch maintenance such as maintenance with pemetrexed will be considered a line of therapy, while use of continuation maintenance such as maintenance with bevacizumab will not be considered a line of therapy. Patients with AC who have received more than two lines of chemotherapy for advanced NSCLC are not eligible. 6. Eastern Cooperative Oncology Group (ECOG) performance status 0-2 after optimization of analgesics 7. Life expectancy = 3 months, and patient expected to receive at least two cycles of therapy at the time of study enrollment 8. Measurable disease by RECIST 1.1 criteria 9.If a patient has had prior or recent radiation therapy: a.Lesion(s) used for determination of RECIST response were not previously or recently irradiated or have documented an increase in size since the completion of the radiotherapy. b.The patient has recovered from any acute effects of the radiotherapy prior to randomization c.Radiotherapy is completed at least 14 days prior to the administration of study drug 10.Hematology values: blood leukocyte count = 3.0 x 10(9)/L, blood absolute neutrophil count = 1.5 x 10(9)/L, blood platelet count = 100 x10(9)/L, hemoglobin = 100 g/L (transfusions are allowed) 11. Clinical chemistry values: plasma total bilirubin level = upper limit of the ”normal” range (ULN; i.e. reference), plasma AST or ALT = 1.5 x ULN (=5 times if liver metastases have been documented) and plasma creatinine = 2.0 x ULN 12. 12-lead ECG with normal tracings; or changes that were not clinically significant and did not require medical intervention 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 45 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 95
Exclusion criteria
Exclusion criteria: 1. Mixed histology of squamous and non-squamous NSCLC 2. Lung tumors assessed by the local radiologist as centrally located and/or involvement of any large blood vessels in the mediastinum. 3. Presence of any endo-bronchial lesions 4. Recent hemoptysis of = 1 tsf (tablespoon full ~ 15ml) within the past 14 days 5. Recent (within past 2 weeks) or current use of anticoagulation therapy or any known coagulopathy or bleeding diathesis. (Patients on anticoagulation therapy for a thromboembolic event should not stop anticoagulation therapy to become eligible for the trial.) 6. Ongoing infection or other major recent or ongoing disease that, according to the Investigator, poses an unacceptable risk to the patient 7. Known primary or secondary central nervous system malignancy. (Patients with symptoms suggestive of possible CNS metastasis such as headache, dizziness or focal neurological deficits should undergo CT or MRI of the brain to rule out CNSmetastasis. Patients who do not have CNS symptoms do not need a CT or MRI of the brain.) 8. Active or previously treated carcinomatous meningitis 9. Truly non-measurable disease by RECIST 1.1 criteria, such as patients with one or more of the following without any RECIST measurable disease: a. Bone lesions b. Ascites c. Pleural or pericardial effusion d. Lymphangitis cutis or pulmonis e. Cystic lesions 10. Grade 3 or higher constipation within the past 28 days or grade 2 constipation within the past 14 days before randomization. (Patients with grade 2 constipation within the past 14 days could be re-screened if constipation decreases to = grade 1 with optimal management of constipation.) 11. Active hepatitis B, active hepatitis C, or known HIV infection 12. Coexisting uncontrolled medical condition, including active cardiac disease (such as unstable angina, myocardial infarction within six months, or New York Heart Association Class III/IV congestive heart failure), and significant dementia 13. Hepatic impairment as indicated by abnormalities of transaminases (AST and/or ALT > 1.5 × ULN or AST and/or ALT >5 times ULN if liver metastases have been documented) and/or increased alkaline phosphatase (> 2.5 × ULN) considered as a result of hepatic impairment (and not from bone disease) 14. History of cancer that has required treatment or been active within the past 5 years, other than NSCLC, basal cell carcinoma, or cervical carcinoma in situ 15. Major surgical procedure within 4 weeks prior to randomization 16. More than one prior anti-tumor systemic therapy for advanced squamous NSCLC, and more than two prior lines of chemotherapy for advanced adneocarcinoma NSCLC 17. Previous use of docetaxel in any line of therapy 18. Women of child bearing potential (WOCBP) who do not consent to using acceptable methods of contraception (i.e. two of the following – oral contraception, barrier contraception, intrauterine device). For purposes of this study, WOCBP include any female who has experienced menarche, who has not undergone tubal ligation, and who is not postmenopausal. Post menopause is defined as: amenorrhea = 12 consecutive months without another cause. 19. Women who are breast-feeding or have a positive pregnancy test at screening 20. Men who are capable of fathering a child and do not agree to using acceptable methods of contraception (such as barrier contraception or abstinence) during the study and for at least six months after the last dose of study drug. Men are considered ca
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the rate of progression-free survival (PFS) at 12 weeks between patients treated with AXL1717 (AXL) and patients treated with docetaxel (DCT) in the total study population and in the SCC and AC subtypes of NSCLC;Secondary Objective: To compare: 1. the rate of complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), disease control (CR+PR+SD), objective response (CR + PR) at 12 weeks between patients treated with AXL1717 (AXL) and patients treated with docetaxel (DCT) 2.the median time to disease progression, time to objective response and time to treatment failure 3.the median duration of progression-free-survival, objective response and disease control 4.12-week survival, one-year survival and overall survival 5.the toxicity profile between the AXL and the DCT treatment groups in the total study population and in each subtype;Primary end point(s): The rate of progression-free survival at 12 weeks following the first dose of study drug is the primary efficacy endpoint.;Timepoint(s) of evaluation of this end point: Baseline and 12-week CT scans assessed by the central reading center will be used for primary efficacy assessments. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Rates of complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), disease control (CR + PR + SD), and objective response (CR + PR) after four cycles (12 weeks) of study treatment • Time to progression (TTP) • Time to treatment failure (TTF) • Time to time to objective response • Progression-free survival • Duration of objective response and duration of disease control • 12-week survival, one-year survival and overall survival (OS);Timepoint(s) of evaluation of this end point: Evaluation (per RECIST 1.1) to be performed at baseline, end of Cycle 2 and at the 12-week assessment (generally after Cycle 4) or at the End of Study visit if prematurely withdrawn during Week 8-12. In the extension period evaluation to be performed after every second cycle or last cycle completed. | — |
Countries
Belarus, Hungary, Poland, Russian Federation, Ukraine
Contacts
Public ContactMedical monitor
PSI Co. Ltd.
Outcome results
None listed