A Phase 1 Study of AMG 208 in Subjects With Advanced Solid Tumors

• Status: Completed
• Trial end date: 2014-12-01
• Target enrollment: 0
• Participant gender: All

Summary

First in human, open-label, sequential dose escalation and expansion study of AMG 208 in subjects with advanced solid tumors.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Amgen

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