A clinical study in non small cell lung cancer investigating whether a new product added to an existing treatment has beneficial effects.

• Conditions: on-small cell lung cancer; MedDRA version: 14.1Level: PTClassification code 10029522Term: Non-small cell lung cancer stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 14.1Level: PTClassification code 10029521Term: Non-small cell lung cancer stage IIIBSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 14.1Level: PTClassification code 10059515Term: Non-small cell lung cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2010-020916-12-DE
• Lead Sponsor: Astellas Pharma Global Development, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-10-20
• Last Update Posted: 16 November 2015

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

1. Histologically confirmed locally advanced or metastatic stage IIIB or IV NSCLC;
2. Have experienced CR, PR or SD following completion of 4 cycles of first-line platinum-based chemotherapy and are not progressing at time of entry into study (prior completed first-line combination bevacizumab therapy is permitted however, current use of maintenance bevacizumab is not permitted);
3. A maximum interval of 28 days between the last day of the treatment cycle and
randomization;
4. Patient has recovered from prior chemotherapy-related toxicity to = grade 2;
5. EGFR mutation status must be confirmed for participation in the study. EGFR analysis can be performed either by central or local laboratory. If analysis is done locally, verifiable documentation confirming the EGFR mutation status must be submitted for review and approval by APGD prior to randomization. If no local result is available, formalin-fixed, paraffin-embedded archival tissue representative of the tumor or in the absence of archival tissue, a fresh tumor tissue sample of sufficient size to perform EGFR mutation analysis must be submitted centrally. Results of the central analysis must be available prior to randomization. Additionally, subjects should provide tissue blocks centrally for biomarker analysis whenever possible. Ideal tissue requirement: block with =5 mm2 tumor area sufficient to provide four 4-micron, and five 10-micron sections;
6. Measurable disease (for those patients with SD or PR following 4 cycles of first-line
platinum based chemotherapy) according to RECIST (version 1.1);
7. Age = 18 years;
8. ECOG PS 0 – 1 (Appendix 13-2);
9. Previous adjuvant or neo-adjuvant treatment is permitted;
10. Must be able to take oral medication;
11. Fasting glucose = 150 mg/dL (8.3 mmol/L). Concurrent use of non-insulinotropic
antihyperglycemic therapy is permitted if the dose has been stable for = 4 weeks at the time of randomization;
12. Adequate hematopoietic, hepatic, and renal function defined as follows:
• Neutrophil count = 1.5 x 109/L;
• Platelet count = 100 x 109/L;
• Bilirubin = 1.5 x ULN;
• AST and ALT = 2.5 x ULN, or = 5 x ULN if patient has documented liver metastases;
• Serum creatinine = 1.5 x ULN
• Potassium, magnesium and calcium within normal limits (supplementation and retesting is permitted).
13. Female patient must be either:
•Of non child bearing potential:
- post-menopausal (defined as at least 1 year without any menses) prior toScreening, or
- documented surgically sterile or status post hysterectomy (at least 1 month prior to Screening)
•Or, if of childbearing potential:
- must have a negative urine pregnancy test at Screening, and
- must use two forms of birth control (one of which must be a barrier method) starting at Screening and throughout the study period and for 180 days after final study drug administration
•Acceptable forms include:
- Established use of oral, injected or implanted hormonal methods of contraception
- Placement of an intrauterine device (IUD) or intrauterine system (IUS)
- Barrier methods of contraception: Condon OR Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository;
14. Female patient must not be breastfeeding at Screening or during the study period and for
180 days after final study drug administration;
15. Female patient must not donate ova starting at Screening and throughout the study period
and for 180 days after final study drug administr

Exclusion Criteria

1. Prior exposure to agents directed at the HER axis (e.g., erlotinib, gefitinib, cetuximab, and trastuzumab);
2. Malignancies other than NSCLC within past 3 years (exceptions if curatively treated: basal or squamous cell carcinoma of skin; locally advanced prostate cancer; ductal carcinoma in situ of breast; in situ cervical carcinoma; and superficial bladder cancer);
3. Type 1 diabetes mellitus or Type 2 diabetes mellitus currently requiring insulinotropic or insulin therapy;
4. Prior IGF-1R inhibitor therapy;
5. Participated in any interventional clinical study or has been treated with any investigational drugs within 30 days or 5 half lives whichever is longer, prior to the initiation of Screening or during the course of the study;
6. Concurrent use of maintenance bevacizumab;
7. History of poorly controlled gastrointestinal disorders that could affect the absorption of study drug (e.g., Crohn’s disease, ulcerative colitis, etc);
8. History (within last 180 days) of significant cardiovascular disease unless the disease is
well-controlled. Significant cardiac disease includes second/third degree heart block;
clinically significant ischemic heart disease; superior vena cava (SVC) syndrome; poorly
controlled hypertension; congestive heart failure of New York Heart Association (NYHA) Class II or worse (slight limitation of physical activity; comfortable at rest, but ordinary physical activity results in fatigue, palpitation, or dyspnea);
9. History of arrhythmia (multifocal premature ventricular contractions [PVCs], bigeminy, trigeminy, ventricular tachycardia, or uncontrolled atrial fibrillation) that is symptomatic or requires treatment (= grade 3), left bundle branch block (LBBB), or asymptomatic sustained ventricular tachycardia are not allowed. Patients with atrial fibrillation controlled by medication are not excluded;
10. Mean QTcF interval = 450 msec based on independent central reviewer analysis of
screening visit ECGs;
11. Use of drugs that have a known risk of causing Torsades de Pointes (TdP) (‘Torsades List’on www.azcert.org/medical-pros/drug-lists/bycategory.cfm, see Appendix 13-3) are
prohibited within 14 days prior to randomization;
12. Use of the potent CYP1A2 inhibitors ciprofloxacin and fluvoxamine. Other less potent CYP1A2 inhibitors/inducers are not excluded;
13. Use of potent CYP3A4 inhibitor such as ketoconazole, clarithromycin, atazanavir,
indinavir, itraconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin,
troleandomycin (TAO), or voriconazole;
14. Use of proton pump inhibitors such as omeprazole. H2-receptor antagonists such as
ranitidine are not excluded;
15. History of cerebrovascular accident (CVA) within 180 days prior to randomization or that resulted in ongoing neurologic instability;
16. Active infection, serious underlying medical condition (including any type of active seizure disorder within 12 months prior to randomization), or serious chronic illness that would impair the ability of the patient to receive study drug;
17. History of any psychiatric or neurologic condition that might impair the patient’s ability to understand or to comply with the requirements of the study or to provide informed consent;
18. Pregnant or breast-feeding females;
19. Symptomatic brain metastases that are not stable, require steroids, are potentially
life-threatening, or that have required radiation and/or other related treatment (e.g., antiepileptic medication) within 21 days

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified