A Pharmacodynamic Study of AV-299 (Formerly SCH 900105) in Subjects With Advanced Solid Tumors Who Have Liver Metastases

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AVEO Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT00969410
First received: August 31, 2009
Last updated: April 11, 2012
Last verified: April 2012
  Purpose

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.


Condition Intervention Phase
Malignant Solid Tumour
Liver Metastases
Biological: AV-299
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacodynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pharmacodynamic Study of AV-299 (Formerly SCH 900105) in Subjects With Advanced Solid Tumors Who Have Liver Metastases (P05670)

Resource links provided by NLM:


Further study details as provided by AVEO Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
    Peripheral blood analysis, liver tissue analysis, and PET

  • 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. ] [ Designated as safety issue: Yes ]
    Dose-limiting toxicities.


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: No ]
  • 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: ] [ Designated as safety issue: No ]

Enrollment: 19
Study Start Date: August 2009
Study Completion Date: March 2011
Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Biological: AV-299
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 Name: Ficlatuzumab, Formerly SCH900105

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00969410

Locations
Spain
Investigational Site 1
Barcelona, Spain
Sponsors and Collaborators
AVEO Pharmaceuticals, Inc.
Investigators
Study Director: Shefali Agarwal, MD AVEO Pharmaceuticals, Inc.
  More Information

No publications provided

Responsible Party: AVEO Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT00969410     History of Changes
Other Study ID Numbers: P05670
Study First Received: August 31, 2009
Last Updated: April 11, 2012
Health Authority: Spain: Agencia Española de Medicamentos y Productos Sanitarios

Keywords provided by AVEO Pharmaceuticals, Inc.:
Neoplasms
Neoplasm metastasis
Liver neoplasms
Neoplastic processes
Pathologic processes
Digestive system neoplasms
Neoplasms by site
Digestive system diseases
Liver diseases

Additional relevant MeSH terms:
Neoplasm Metastasis
Neoplasms, Second Primary
Neoplasms
Liver Neoplasms
Neoplastic Processes
Pathologic Processes
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases

ClinicalTrials.gov processed this record on August 19, 2014