- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00969410
A Pharmacodynamic Study of AV-299 (Formerly SCH 900105) in Subjects With Advanced Solid Tumors Who Have Liver Metastases
A Pharmacodynamic Study of AV-299 (Formerly SCH 900105) in Subjects With Advanced Solid Tumors Who Have Liver Metastases (P05670)
A pharmacodynamic study to evaluate the effect of AV-299 on exploratory pharmacodynamic markers in subjects with advanced solid tumors who have liver metastases.
To evaluate safety and tolerability of AV-299 administered IV in subjects with advanced solid tumors who have liver metastases.
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
-
Barcelona, Spain
- Investigational site 1
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Ability to give written informed consent and be able to adhere to dose and visit schedules.
- Diagnosis of an advanced colorectal, breast, gastric/esophageal or pancreatic cancer with liver metastases that are amenable to biopsy.
- Histological or cytological evidence of malignancy.
- Advanced metastatic colorectal, breast, gastric/esophageal or pancreatic cancer that has recurred or progressed following standard therapy or failed standard therapy; or for which no standard therapy currently exists, or for which subject is not a candidate for, or is unwilling to undergo standard therapy.
Note: Additional tumor histologies may be eligible based on available HGF/c-Met pathway data and approval by the Sponsor.
- Disease that is currently not amenable to curative surgical intervention.
- Male or female and ≥ 18 years of age.
- ECOG performance status of 0-1.
- Measurable p-Met by immunohistochemistry in archived or otherwise available tumor sample.
- Female subjects of childbearing potential must have negative pregnancy test within 5 days prior to first dose of study drug.
- Female subjects of childbearing potential and male subjects whose sexual partners are of childbearing potential must agree to abstain from sexual intercourse or to use an effective method of contraception during the study and for 60 days after the last dose of AV-299 (formerly SCH 900105). Examples of effective methods of contraception include oral contraceptives or double barrier methods such as condom plus spermicide or condom plus diaphragm.
- Adequate hematologic function as evidenced by Hg ≥ 9g/dL, WBC ≥ 3000 per mm3, ANC ≥ 1500 per mm3 and platelet count ≥ 100,000 per mm3.
- Adequate hepatic function as evidenced by a serum bilirubin level ≤ 1.5 × ULN (except with known Gilbert's Syndrome) and with serum AST/ALT levels ≤ 5 × ULN.
- Adequate renal function as evidenced by a serum creatinine level ≤ 1.5 × ULN or a calculated creatinine clearance > 60 mL/min.
- Adequate coagulation function as evidenced by PTT ≤ 1.5 × ULN and INR ≤ 1.5 × ULN.
- Recovery from the effects of any prior surgery, radiotherapy, or systemic antineoplastic therapy.
- Subjects with abnormal liver function tests (LFTs) who have not been screened for Hepatitis B or C within the past 6 months prior to study enrollment, will need to be screened for Hepatitis B and C and can only be enrolled if the screening is negative.
Exclusion Criteria:
- Women who are breast-feeding, pregnant, or intend to become pregnant.
- Hematologic malignancies.
- Any of the following within 6 months prior to administration of study drug:
- Myocardial infarction (MI), severe/unstable angina pectoris, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack or seizure disorder.
- Serious/symptomatic active infection, or infection requiring antibiotics, within 14 days prior to first dose of study drug.
- Persistent, unresolved CTCAE v3.0 Grade 2 or higher drug-related toxicity (except alopecia, erectile dysfunction, hot flashes, decreased libido, and Grade 2 sensory peripheral neuropathy) associated with previous treatment.
- Inadequate recovery from any prior surgical procedure or major surgical procedure performed within 4 weeks prior to administration of first dose of study drug.
- Any other medical or psychiatric condition that, in the opinion of the investigator, might interfere with the subject's participation in the trial or interfere with the interpretation of trial results.
- Known Human Immunodeficiency Virus (HIV) infection or a known HIV-related malignancy.
- Known active hepatitis B or C.
- Known hypersensitivity to any of the components of SCH 900105.
- Known bleeding diathesis.
- Radiotherapy within 3 weeks prior to first study drug administration.
- Inability to comply with the protocol requirements, including inability to undergo liver biopsies.
- Participation in any other clinical trials involving therapeutic agents.
- Any medications prohibited in the study.
- Active alcohol or illicit drug abuse.
- Stem cell/bone marrow transplant within 6 months of first dose of study drug.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: AV-299 administered IV (monotherapy)
Subjects will be enrolled sequentially and treated with AV-299 (formerly SCH 900105) in dose escalating cohorts.
Accrual to the next cohort will occur only if <= 1 out of 6 subjects experiences a dose-limiting toxicity (DLT) during the first 2 cycles.
If >= 2 subjects in the same dose cohort experience a DLT during the first 2 cycles, dose-escalation will be terminated.
|
AV-299 will be given as an intravenous infusion in dose-escalating doses of 2, 10, and 20 mg/kg once every 2 weeks.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
To evaluate the effect of AV-299 (formerly SCH 900105) on exploratory pharmacodynamic markers in subjects with advanced solid tumors who have liver metastases
Time Frame: Screening Cycle 1: Day 1, Day 3-4: Cycle 2: Day 1 Cycle 3: Day 8-14
|
Peripheral blood analysis, liver tissue analysis, and PET
|
Screening Cycle 1: Day 1, Day 3-4: Cycle 2: Day 1 Cycle 3: Day 8-14
|
To evaluate safety and tolerability of AV-299 (formerly SCH 900105) administered IV in subjects with advanced solid tumors who have liver metastases
Time Frame: DLTs assessed during first 4 weeks of treatment.
|
Dose-limiting toxicities.
|
DLTs assessed during first 4 weeks of treatment.
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
To evaluate the PK of AV-299 (formerly SCH 900105) in subjects with advanced solid tumors who have liver metastases
Time Frame: Cycle 1: Day 1, Day 3-4 Cycle 2: Day 1 Cycle 3: Day 1, Day 8-14
|
Cycle 1: Day 1, Day 3-4 Cycle 2: Day 1 Cycle 3: Day 1, Day 8-14
|
To study the preliminary antineoplastic activity of AV-299 (formerly SCH 900105) in subjects with advanced solid tumors who have liver metastases
Time Frame: Subjects will undergo disease assessment at screening (within 4 weeks prior to first dose of study drug), the Cycle 3 Day 8-14 visit, and approximately every 6 weeks thereafter.
|
Subjects will undergo disease assessment at screening (within 4 weeks prior to first dose of study drug), the Cycle 3 Day 8-14 visit, and approximately every 6 weeks thereafter.
|
To investigate the effect of AV-299 (formerly SCH 900105) on gene expression patterns in peripheral blood mononuclear cells and liver biopsies in subjects with advanced solid tumors who have liver metastases
Time Frame: Cycle 1: Day 1, Day 3-4 Cycle 3: Day 8-14:
|
Cycle 1: Day 1, Day 3-4 Cycle 3: Day 8-14:
|
Collaborators and Investigators
Sponsor
Investigators
- Study Director: Shefali Agarwal, MD, AVEO Pharmaceuticals, Inc.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- P05670
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Liver Metastases
-
Society of Interventional OncologyRecruitingColorectal Liver MetastasesUnited States, Netherlands, Greece
-
Memorial Sloan Kettering Cancer CenterCompletedLocalize Liver MetastasesUnited States
-
Heidelberg UniversityUnknownColorectal Liver MetastasesGermany
-
Dr. M.R. MeijerinkAmsterdam UMC, location VUmcCompletedColorectal Liver Metastases | Metastatic Liver DiseaseNetherlands
-
University of ZurichCompletedColorectal Liver MetastasesSwitzerland, France, Spain
-
Assistance Publique - Hôpitaux de ParisNot yet recruitingUnresectable Colorectal Liver MetastasesFrance
-
Peking University Cancer Hospital & InstituteRecruitingColorectal Liver MetastasesChina
-
Amsterdam UMC, location VUmcCompletedColorectal Liver MetastasesNetherlands
-
David BartlettNational Cancer Institute (NCI); National Institutes of Health (NIH)CompletedColorectal Liver MetastasesUnited States
-
University of MilanCompleted
Clinical Trials on AV-299
-
AVEO Pharmaceuticals, Inc.No longer availableMullerian Mixed Tumor of OvaryUnited States
-
AVEO Pharmaceuticals, Inc.CompletedMultiple Myeloma | Lymphomas | Malignant Solid TumorUnited States
-
AVEO Pharmaceuticals, Inc.RecruitingRecurrent Head and Neck Squamous Cell Carcinoma | Metastatic Head-and-neck Squamous-cell CarcinomaUnited States, Australia
-
Huazhong University of Science and TechnologyUnknown
-
Julie E. Bauman, MD, MPHAVEO Pharmaceuticals, Inc.TerminatedCarcinoma, Squamous Cell of Head and NeckUnited States
-
AVEO Pharmaceuticals, Inc.CompletedLung Neoplasms | Respiratory Tract Neoplasms | Lung Cancer | Carcinoma, Non-Small Cell-LungHong Kong, Korea, Republic of, Malaysia, Philippines, Singapore, Taiwan, Thailand
-
University Hospital, Gentofte, CopenhagenRigshospitalet, Denmark; Lund University HospitalUnknownHeart Failure | Ischemic CardiomyopathyDenmark, Sweden
-
Region SkaneLund UniversityCompletedAdvanced ENT Surgery | Microbiological Flora in the Oropharynx and Lower AirwaysSweden
-
Northwestern UniversityNational Institute on Aging (NIA)RecruitingPrimary Progressive Aphasia With Suspected Alzheimer's DiseaseUnited States
-
Region SkaneLund UniversityTerminatedClostridium Difficile Colonisation | Impact of Enteral Probiotics on Certain Lab ParametersSweden