An Open-label, Randomized Phase 3 Efficacy Study of ASP8273 vs. Erlotinib or Gefitinib in First-line Treatment of Patients with Stage IIIB/IV Non-small Cell Lung Cancer Tumors with EGFR Activating Mutations (SOLAR Study)
- Conditions
- on-small Cell Lung Cancer TumorsMedDRA version: 18.1Level: LLTClassification code 10025054Term: Lung cancer non-small cell stage IIIBSystem Organ Class: 100000004864MedDRA version: 18.1Level: LLTClassification code 10025055Term: Lung cancer non-small cell stage IVSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2015-002894-39-ES
- Lead Sponsor
- Astellas Pharma Global Development, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 540
Subject must meet all of the following inclusion criteria to be eligible for participation in this study at enrollment:
1. Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written informed consent and privacy language as per national regulations (e.g., HIPAA Authorization for U.S. sites) must be obtained from the subject or legally authorized representative prior to any
study-related procedures.
2. Subject is >/= 18 years of age and legally an adult according to local regulation at the time of signing informed consent.
3. Subject agrees not to participate in another interventional study while on treatment.
4. Female subject must either:
Be of nonchildbearing potential:
- postmenopausal (defined as at least 1 year without any menses) prior to Screening, or
- documented surgically sterile
Or, if of childbearing potential:
- Agree not to try to become pregnant during the study and for 28 days after the final study drug administration
- And have a negative serum pregnancy test at Screening
- And, if heterosexually active, agree to consistently use 2 forms of highly effective birth control* (at least 1 of which must be a barrier method) starting at Screening and throughout the study period and for 28 days after the final study drug administration
5. Female subject must not be breastfeeding at Screening or during the study period, and for 28 days after the final study drug administration.
6. Female subject must not donate ova starting at Screening and throughout the study period, and for 28 days after the final study drug administration.
7. Male subject and their female spouse/partners who are of childbearing potential must be using highly effective contraception consisting of 2 forms of birth control* (1 of which must be a barrier method) starting at Screening and continue throughout the study period and for 90 days after the final study drug administration.
*Highly effective forms of birth control include:
- Consistent and correct usage of established oral, injected or implanted hormonal methods of contraception
- Established intrauterine device (IUD) or intrauterine system (IUS)
- Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository
8. Male subject must not donate sperm starting at Screening and throughout the study period and for 90 days after the final study drug administration.
9. Subject has Eastern Cooperative Oncology Group (ECOG) performance status 10. Subject has histologically confirmed locally advanced, metastatic or unresectable Stage IIIB/IV adenocarcinoma NSCLC (newly diagnosed or recurrent). Subjects with mixed histology are eligible if adenocarcinoma is the predominant histology.
11. Subject has predicted life expectancy >/= 12 weeks in the opinion of the investigator.
12. Subject must meet all of the following criteria on the laboratory tests that will be analyzed centrally within 7 days prior to the first dose of study drug. In case of multiple laboratory data within this period, the most recent data should be used.
- Neutrophil count > 1,000/mm^3
- Platelet count >/= 7.5 x 10^4 /mm^3
- Hemoglobin > 8.0 g/dL
- Serum creatinine < 2.0 x upper limit of normal (ULN) or an estimated glomerular filtration rate (eGFR) of > 50 mL/min as calculated by the Cockcroft Gault Method
Total bilirubin < 1.5 x ULN (except for subjects with documented Gilbert?s syndrome)
AST and ALT < 3.0 x ULN or </= 5 x ULN if subje
Subject who meets any of the following exclusion criteria prior to enrollment is not eligible for enrollment:
1. Subject has received intervening anticancer treatment or previous treatment with chemotherapy
for metastatic disease. The administration of neoadjuvant or adjuvant chemotherapy is allowed as long as it has finalized >/= 6 months before the first dose of study drug.
2. Subject has received a prior treatment with a therapeutic agent targeting EGFR (e.g., afatinib, dacomitinib, ASP8273, etc).
3. Subject has received investigational therapy within 28 days or 5 half-lives prior to the first dose of study drug.
4. Subject has received radiotherapy within 1 week prior to the first dose of study drug. If the subject received radiotherapy > 1 week prior to study treatment, the irradiated lesion cannot be the only lesion used for evaluating response.
5. Subject has symptomatic central nervous system (CNS) metastasis. Subject with previously treated brain or CNS metastases are eligible provided that the subject has recovered from any acute effects of radiotherapy and is not requiring escalating doses of steroids, and any whole brain radiation therapy was completed at least 2 weeks prior to study drug administration, or any stereotactic radiosurgery (SRS) was completed at least 1 week prior to the first dose of study drug.
6. Subject has received blood transfusions or hematopoietic factor therapy within 14 days prior to the first dose of study drug.
7. Subject has had a major surgical procedure (other than a biopsy) within 14 days prior to the first dose of study drug, or one is planned during the course of the study.
8. Subject has a known history of a positive test for human immunodeficiency virus (HIV) infection.
9. Subject has known history of serious hypersensitivity reaction to a known ingredient of ASP8273, erlotinib or gefitinib.
10. Subject has evidence of an active infection requiring systemic therapy within 14 days prior to the planned first dose of study drug.
11. Subject has severe or uncontrolled systemic diseases including uncontrolled hypertension (blood pressure > 150/100 mmHg) or active bleeding diatheses.
12. Subject has history of drug-induced interstitial lung disease (ILD) or any evidence of active ILD.
13. Subject has ongoing cardiac arrhythmia that is Grade >/= 2 or uncontrolled atrial fibrillation of any
grade.
14. Subject currently has Class 3 or 4 New York Heart Association congestive heart failure.
15. Subject has history of severe/unstable angina, myocardial infarction or cerebrovascular accident within 6 months prior to the planned first dose of study drug.
16. Subject has history of gastrointestinal ulcer or gastrointestinal bleeding within 3 months prior to the planned first dose of study drug.
17. Subject has concurrent corneal disorder or any ophthalmologic condition which, in the investigator?s opinion, makes the subject unsuitable for study participation (i.e., advanced cataracts, glaucoma).
18. Subject has difficulty taking oral medication or any digestive tract dysfunction or inflammatory bowel disease that would interfere with the intestinal absorption of drug.
19. Subject has another malignancy which requires treatment.
20. Subject has any condition which, in the investigator's opinion, makes the subject unsuitable for study participation.
21. Subject has used the following drugs:
a. Potent CYP 3A4 inhibitors within 7 days prior to first dose of study drug
b. Proton pump inhibitors such as omepraz
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the progression free survival (PFS), based on independent radiologic review (IRR), of ASP8273 compared to erlotinib or gefitinib in patients with locally advanced, metastatic or unresectable stage IIIB/IV adenocarcinoma non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) activating mutations.;Secondary Objective: - Overall survival (OS)<br>- Overall response rate (ORR) as assessed by IRR<br>- PFS as assessed by the investigator<br>- Disease control rate (DCR) as assessed by IRR<br>- Safety of ASP8273;Primary end point(s): - PFS as assessed by IRR;Timepoint(s) of evaluation of this end point: Up to 36 months.
- Secondary Outcome Measures
Name Time Method Secondary end point(s): - OS<br>- Best overall response rate (CR + PR) by IRR<br>- PFS by the investigator<br>- DCR (CR+PR+SD) by IRR<br>- Safety variables (e.g., adverse events [AEs], laboratory tests, vital sign measurements, electrocardiograms [ECGs]);Timepoint(s) of evaluation of this end point: Up to 36 months.