Clinical trial NCT00813384: A Phase 1 Study of AMG 208 in Subjects With Advanced Solid Tumors
Official title: A Phase 1, First-In-Human Study Evaluating the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 208 in Adult Subjects With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cancer
Oncology
Tumors
Advanced Malignancy
Advanced Solid Tumors
Oncology Patients
Keywords: Cancer
Solid Tumors
Phase 1
C-met inhibitor
Clinical Trial
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2008-12-23
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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

Primary outcomes:
measure: To determine the maximum tolerated dose (MTD) of AMG 208, if possible
timeFrame: 3.5 years
measure: To evaluate for clinical responses associated with AMG 208 treatment in subjects (Dose Expansion) with advanced solid malignancies according to RECIST criteria
timeFrame: 3.5 years
measure: To characterize the pharmacokinetic (PK) exposure of AMG 208 when administered orally to subjects with advanced solid malignancies
timeFrame: 3.5 years
measure: To evaluate the safety and tolerability of AMG 208 in subjects with advanced solid malignancies
timeFrame: 3.5 years
Secondary outcomes:
measure: 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
timeFrame: 3.5 years
measure: To assess tumor volume changes after AMG 208 treatment by computed tomography (CT) or magnetic resonance imaging (MRI)
timeFrame: 3.5 years
measure: To assess skin specimens for potential biomarkers
timeFrame: 3.5 years
measure: To determine whether c-Met expression, mutation, or amplification in tumor specimens correlates with a response to AMG 208
timeFrame: 3.5 years
Other outcomes:
Locations:
city: Beverly Hills
country: United States
facility: Research Site
state: California
city: St Louis
country: United States
facility: Research Site
state: Missouri
city: Houston
country: United States
facility: Research Site
state: Texas
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: Hong DS, Rosen P, Lockhart AC, Fu S, Janku F, Kurzrock R, Khan R, Amore B, Caudillo I, Deng H, Hwang YC, Loberg R, Ngarmchamnanrith G, Beaupre DM, Lee P. A first-in-human study of AMG 208, an oral MET inhibitor, in adult patients with advanced solid tumors. Oncotarget. 2015 Jul 30;6(21):18693-706. doi: 10.18632/oncotarget.4472.