Clinical trial NCT01221077 (phase 2, status: completed)
Conditions: nsclc, non small cell lung cancer
ICD codes: C78.00, C78.01, C78.02, D14.30, D14.31, D14.32, C34.2
Drugs: osi-906, erlotinib, placebo
SMILES: C[C@@]1(O)C[C@@H](C1)C1=NC(=C2N1C=CN=C2N)C1=CC=C2C=CC(=NC2=C1)C1=CC=CC=C1, COCCOC1=CC2=C(C=C1OCCOC)C(NC1=CC(=CC=C1)C#C)=NC=N2, CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
Eligibility criteria:

        Inclusion Criteria:

          -  Historically confirmed advanced NSCLC stages IIIB or IV

          -  Exon 19 deletion or exon 21 activating mutation in EGFR

          -  EGFR mutation status must be confirmed for participation in the study. EGFR 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 sponsor 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 for biomarker central analysis whenever possible. Ideal
             tissue requirement: block with ≥5 mm2 tumor area sufficient to provide four 4-micron,
             and five 10-micron sections

          -  Measurable disease according to RECIST (version 1.1)

          -  ECOG performance status 0-1

          -  Must be able to take oral medication

          -  Fasting glucose <= 150 mg/dL (8.3 mmol/L). Concurrent use of non-insulinotropic anti
             hyperglycemic therapy is permitted if the dose has been stable for >= 4 weeks at the
             time of randomization

          -  Adequate hematopoietic, hepatic, and renal function as follows:

               -  Neutrophil count >= 1500/uL

               -  Platelet count >= 100,000/uL

               -  Serum creatinine <= 1.5 x Upper Limit of Normal (ULN)

               -  Potassium, magnesium, and calcium within normal limits (supplementation and
                  re-testing is permitted)

               -  Total bilirubin <= 1.5 x ULN

               -  AST and ALT <= 2.5 x ULN, or <= 5 x ULN if patient has documented liver
                  metastases

          -  Female subject must be either:

               -  Of non child bearing potential:

                    1. post-menopausal (defined as at least 1 year without any menses) prior to
                       Screening, or

                    2. documented surgically sterile or status post hysterectomy (at least 1 month
                       prior to Screening).

               -  Or, if of childbearing potential:

                    1. must have a negative urine pregnancy test at Screening, and

                    2. must use two forms of birth control (at least one of which must be a barrier
                       method) starting at Screening and throughout the study period and for 30
                       days after final study drug administration. Acceptable forms include:

                         1. Established use of oral, injected or implanted hormonal methods of
                            contraception;

                         2. Placement of an intrauterine device (IUD) or intrauterine system (IUS);

                         3. Barrier methods of contraception: Condom OR Occlusive cap (diaphragm or
                            cervical/vault caps) with spermicidal foam/gel/film/cream/suppository.

          -  Female subject must not be breastfeeding at Screening or during the study period and
             for 30 days after final study drug administration.

          -  Female subject must not donate ova starting at Screening and throughout the study
             period and for 30 days after final study drug administration.

          -  Male subject and their female spouse/partners who are of childbearing potential must
             be using highly effective contraception consisting of two forms of birth control (one
             of which must be a barrier method) starting at Screening and continue throughout the
             study period and for 30 days after final study drug administration. Acceptable forms
             include:

               1. Established use of oral, injected or implanted hormonal methods of contraception.

               2. Placement of an intrauterine device (IUD) or intrauterine system (IUS).

               3. Barrier methods of contraception: Condom OR Occlusive cap (diaphragm or
                  cervical/vault caps) with spermicidal foam/gel/film/cream/suppository.

          -  Male subjects must not donate sperm starting at Screening and throughout the study
             period and for at least 30 days after final study drug administration.

          -  Patients must provide written informed consent to participate in the study

          -  Patients may not have received chemotherapy for advanced NSCLC. Previous adjuvant
             and/or neoadjuvant treatment for NSCLC is permitted

          -  Prior radiation therapy is permitted provided patients have recovered from the acute,
             toxic effects of radiotherapy prior to randomization. A minimum of 28 days must have
             elapsed between the end of radiotherapy and randomization

          -  Prior surgery is permitted provided that the surgery was done >= 28 days prior to
             randomization and adequate wound healing has occurred prior to randomization

        Exclusion Criteria:

          -  Prior exposure to agents directed at the Human Epidermal Receptor (HER) axis (eg,
             erlotinib, gefitinib, and cetuximab)

          -  Prior insulin-like growth factor -1 receptor (IGF-1R) inhibitor therapy

          -  Malignancies other than NSCLC within the 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)

          -  Diabetes mellitus currently requiring insulinotropic or insulin therapy

          -  Use of proton pump inhibitors such as omeprazole within 14 days prior to
             randomization. H2-receptor antagonists such as ranitidine are not excluded

          -  Symptomatic brain metastases that are not stable, require steroids, or have required
             radiation and/or other related treatment (i.e., anti-epileptic medication) within 21
             days prior to randomization

          -  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.

          -  History of poorly controlled gastrointestinal disorders that could affect the
             absorption of study drug (eg, Crohn's disease or ulcerative colitis)

          -  History (within last 6 months) 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 no ordinary physical activity results in fatigue,
             palpitation, or dyspnea)

          -  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

          -  Mean QTcF interval >= 450 msec at screening

          -  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) are prohibited within
             14 days prior to randomization

          -  Use of strong/moderate CYP1A2 inhibitors such as ciprofloxacin and fluvoxamine. Other
             less potent CYP1A2 inhibitors/inducers are not excluded

          -  Use of strong/moderate CYP3A4 inhibitors and inducers

          -  History of cerebrovascular accident (CVA) within 6 months prior to randomization or
             that resulted in ongoing neurologic instability

          -  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

          -  Pregnant or breast-feeding females

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to the study drug

          -  Active infection, serious underlying medical condition (including any type of active
             seizure disorder within 12 months prior to randomization), symptomatic brain
             metastases, or serious chronic illness that would impair the ability of the patient to
             receive study drug