Advanced Malignancy, Advanced Solid Tumors, Cancer, Oncology, Oncology Patients, Tumors
Conditions
Keywords
Cancer, Solid Tumors, Phase 1, C-met inhibitor, Clinical Trial
Brief summary
First in human, open-label, sequential dose escalation and expansion study of AMG 208 in subjects with advanced solid tumors.
Interventions
DRUGAMG 208
AMG 208 is a small molecule inhibitor of c-Met which is a well-characterized receptor tyrosine kinase expressed on the surface of epithelial cells. C-Met receptor signaling has been shown to play a key role in the survival of cancer cells. AMG 208 inhibits both ligand-dependent and ligand-independent c-Met cellular growth regulation. Inhibition of c-Met signaling with AMG 208 provides a potential mechanism for blocking tumor growth and survival.
Sponsors
Amgen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To evaluate the safety and tolerability of AMG 208 in subjects with advanced solid malignancies | 3.5 years |
| To determine the maximum tolerated dose (MTD) of AMG 208, if possible | 3.5 years |
| To evaluate for clinical responses associated with AMG 208 treatment in subjects (Dose Expansion) with advanced solid malignancies according to RECIST criteria | 3.5 years |
| To characterize the pharmacokinetic (PK) exposure of AMG 208 when administered orally to subjects with advanced solid malignancies | 3.5 years |
Secondary
| Measure | Time frame |
|---|---|
| To evaluate for a decrease in tumor cell proliferation associated with AMG 208 treatment in subjects with advanced solid malignancies according to FLT-PET scanning | 3.5 years |
| To assess tumor volume changes after AMG 208 treatment by computed tomography (CT) or magnetic resonance imaging (MRI) | 3.5 years |
| To assess skin specimens for potential biomarkers | 3.5 years |
| To determine whether c-Met expression, mutation, or amplification in tumor specimens correlates with a response to AMG 208 | 3.5 years |
Countries
United States
Outcome results
None listed