a phase 1 study of amg 208 in subjects with advanced solid tumors

Conditions: Cancer; Oncology; Tumors; Advanced Malignancy; Advanced Solid Tumors; Oncology Patients

Summary: first in human, open-label, sequential dose escalation and expansion study of amg 208 in subjects with advanced solid tumors.


Eligibility criteria:
inclusion criteria: * men or women ≥ 18 years old * subjects must have a pathologically documented, definitively diagnosed, advanced solid tumor that is refractory to standard treatment, for which no standard therapy is available or the subject refuses standard therapy * measurable disease per recist guidelines (subjects with non-measurable, but evaluable disease are also eligible for part 1 of the study) * eastern cooperative oncology group (ecog) performance status of ≤ 2 * life expectancy of \> 3 months, in the opinion of the investigator * female subjects who are post-menopausal (no menstrual period for a minimum of 12 months), or surgically sterilized. female subjects of child bearing potential must remain abstinent or use double-barrier birth control method during the period of therapy and must be willing to use contraception 2 weeks following the last study drug administration and have a negative serum pregnancy test upon entry into this study * male subject is willing to use contraception upon enrollment, during the course of the study and for 12 weeks following the last study drug administration * willing to provide tumor samples and / or slides * competent to sign and date an institutional review board approved informed consent form * hematological function, as follows: absolute neutrophil count (anc) ≥ 1.5 x 109/l platelet count ≥ 100 x 109/l hemoglobin \> 9 g/dl prothrombin time (pt) or partial thromboplastin time (ptt) \< 1.5 x institutional upper limit of normal (iuln) * renal function, as follows: serum creatinine \< 2.0 mg/dl * hepatic function, as follows: ast/alt \< 3x uln and total bilirubin \< 1.5x uln in all subjects alkaline phosphatase \< 2.0 x uln (if liver or bone metastases are present, ≤ 5 x uln) exclusion criteria: * any disorder that compromises the ability of the subject to give written informed consent and/or to comply with the study procedures. * primary central nervous system (cns) tumors or metastases * history of bleeding diathesis * myocardial infarction within 6 months of study day 1, symptomatic congestive heart failure (new york heart association \> class ii), unstable angina, or unstable cardiac arrhythmia requiring medication, or uncontrolled hypertension in the opinion of the investigator * a baseline ecg qtc \> 480 ms * active infection within 2 weeks of study enrollment (day 1) * significant gastrointestinal disorder(s), in the opinion of the investigator, (e.g. crohn's disease, ulcerative colitis, extensive gastrointestinal resection) that may influence drug absorption * known positive test for hiv * known acute or chronic hepatitis b or hepatitis c infection, determined by serologic tests * unresolved toxicities from prior anti-tumor therapy, defined as not having resolved to ctcae grade 0 or 1, or to levels dictated in the eligibility criteria with the exception of alopecia * anti-tumor therapy (chemotherapy, antibody therapy, molecular targeted therapy, retinoid therapy, hormonal therapy, or investigational agent) within 28 days of study day 1 (six weeks for nitrosureas, mitomycin c, or antibody or molecular targeted agents with t1/2 \> 10 days); concurrent use of hormone deprivation therapy for hormone-refractory prostate cancer or breast cancer is permitted * treatment with immune modulators including, but not limited to, systemic corticosteroids, cyclosporine and tacrolimus within two weeks prior to enrollment * therapeutic or palliative radiation therapy within 2 weeks of study day 1 * concurrent or prior (within 7 days of study day 1) anticoagulation therapy (low-dose warfarin \[≤ 2 mg/day\] or low molecular weight heparins for prophylaxis against central venous catheter thrombosis or aspirin \[81 mg/day\] is allowed) * prior participation in an investigational study and/or procedure within 28 days of study day 1 * major surgery within 30 days of study day 1 * any co-morbid medical disorder that may increase the risk of toxicity, in the opinion of the investigator or sponsor

Keywords: cancer solid tumors phase 1 c-met inhibitor clinical trial