A Phase 1 Dose-Escalation Study in Advanced Solid Tumors, Lymphomas or Multiple Myeloma

NCT00725634 | Completed Phase 1

• 1 other identifier: P05538
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 3

Brief Summary

Phase 1 study to determine safety, tolerability, dose-limiting toxicities (DLTs), and recommended Phase 2 dose of AV-299 administered IV as monotherapy to patients with relapsed or refractory solid tumors, lymphoma, or multiple myeloma. The study will also determine the safety, tolerability and DLTs of AV-299 in combination with erlotinib in patients with relapsed or refractory solid tumors.

Conditions

Malignant Solid Tumor; Lymphomas; Multiple Myeloma

Keywords

Neoplasms,; Lymphoma,; Multiple Myeloma,; Neoplasms, Plasma Cell,; Neoplasms by Histologic Type,; Lymphoproliferative Disorders,; Lymphatic Diseases, Immunoproliferative Disorders; Immune System Diseases Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Erlotinib; Protein Kinase Inhibitors; Enzyme Inhibitors,; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions

Outcome Measures

Primary Outcomes (1)

• Dose Limiting Toxicity and Recommended Phase 2 dose

  Assessment of any dose-limiting toxicity

  Following 4 weeks of treatment

Secondary Outcomes (6)

• Pharmacokinetic (PK) profile of AV-299, and erlotinib (for subjects enrolled in the Phase 1b only).

  Cycle 1: Day 1-4, Day 8 Cycle 2: Day 1, Day 8 Cycle 3: Day 1 Cycle 4: Day 8-14 Subsequent Cycles to Cycle 52: Day 1 End of Treatment Visit 1-Month and 2-Month Follow-Up Visits

• Evaluate the effects of AV-299 and combination of AV-299 and erlotinib on exploratory biomarkers in blood, body fluid, tumor tissue, and/or bone marrow.

  Screening Cycle 1: Day 1-4, Day 8 Cycle 2: Day 1, Day 8-14 Cycle 4: Day 8-14

• Study the preliminary antineoplastic activity of AV-299 in subjects with advanced solid tumors, lymphoma, or multiple myeloma, and the preliminary antineoplastic activity of AV 299 in combination with erlotinib in subjects with advanced solid tumor.

  Advanced solid tumors and lymphoma, every 8 weeks through Cycle 29, and approximately every 12 weeks thereafter. Subjects with multiple myeloma will undergo disease assessment at screening and approximately every 4 weeks after Day 1.

• Investigate the effect of AV-299 and of the combination of AV-299 and erlotinib on gene expression patterns in peripheral blood mononuclear cells and/or bone marrow.

  Cycle 1: Day 1-4 Cycle 4: Day 8-14

• Assess dosing schedules of AV-299 (e.g. every 2-week and every 3-week schedules).

  Throughout the study

Study Arms (2)

AV-299 Dose Escalation Arm

EXPERIMENTAL

AV-299 Administered by IV Infusion as Monotherapy in Advanced Solid Tumors, Lymphomas, or Multiple Myeloma

Biological: AV-299

AV-299 in combination with erlotinib

EXPERIMENTAL

AV-299 Administered by IV Infusion in Combination with Erlotinib (150 mg daily) in Advanced Solid Tumors

Biological: AV-299 + erlotinib

Interventions

AV-299 BIOLOGICAL

AV-299 monotherapy will be given as intravenous infusion in dose-escalation cohorts at 2, 5, 10, and 20 mg/kg. Once the RP2D has been determined the cohort may be expanded to include up to 12 patients for safety assessment and enriched with up to 12 additional Multiple Myeloma patients.

Also known as: Formerly SCH 900105

AV-299 Dose Escalation Arm

AV-299 + erlotinib BIOLOGICAL

AV-299 will be given as intravenous infusion at RP2D in combination with erlotinib (150 mg daily). Once the combination-RP2D has been determined the cohort may be expanded to include up to 12 additional patients.

Also known as: Formerly SCH 900105

AV-299 in combination with erlotinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of an advanced solid tumor malignancy or lymphoma (non-Hodgkin's or Hodgkin's lymphoma).
• Histological or cytological evidence of malignancy.
• Advanced malignancy, metastatic or unresectable, 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.
• Disease that is currently not amenable to curative surgical intervention.
• ECOG performance status of 0-1. Subjects with performance status of 2 will be considered only after discussion between the investigator and medical monitor.
• years or older, of either sex, and of any race.
• Subject (and/or parent/guardian for subject who otherwise is unable to provide independent consent, if acceptable to and approved by the site and/or site's IRB) must be willing to give written informed consent and be able to adhere to dose and visit schedules.
• 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, but are not limited to, 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
• For subjects in the dose-escalation cohorts and the Phase 1b evaluation of AV-299 (formerly SCH 900105) in combination with erlotinib:
• \-- Serum AST/ALT levels ≤3 × ULN for the reference laboratory
• For subjects in the RP2D safety expansion cohort:
• Without known hepatic metastasis serum AST/ALT levels ≤3 × ULN for the reference laboratory

You may not qualify if:

• Women who are breast-feeding, pregnant, or intend to become pregnant.
• Subjects with primary CNS malignancy or symptomatic CNS metastases, with the exception that subjects with glioblastoma multiforme may be enrolled in the RP2D Safety Expansion Cohort and in the Phase 1b evaluation of AV-299 (formerly SCH 900105) in combination with erlotinib. Subjects with treated brain metastases that have remained stable for at least 3 months without steroids are allowed. Subjects with signs or symptoms or history of brain metastasis must have a CT or MRI scan of the brain within 1 month prior to the first dose of study drug. Subjects with spinal cord or nerve root compression who have completed treatment at least 4 weeks prior to the first dose of study drug and are stable without steroid treatment for at least 1 week prior to the first dose of study drug are allowed. Subjects with leptomeningeal metastases are not allowed.
• Hematologic malignancies other than lymphoma
• 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 and/or symptomatic active infection within 14 days prior to first dose of study drug. Subjects who have asymptomatic or mild infection and taking a short course of antibiotics (ie, UTI, bronchitis) may be allowed after discussion with the medical monitor.
• Baseline QTc interval as follows per Bazett's formula: Females \> 470 msec; Males \> 450 msec.
• Persistent, unresolved CTCAE v3.0 Grade 2 or higher drug-related toxicity (except alopecia, erectile dysfunction, hot flashes, and decreased libido) 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 or major surgery within 3 weeks prior to 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 AV-299 (formerly SCH 900105).
• Radiotherapy within 3 weeks prior to first study drug administration.
• Inability to comply with the protocol requirements or participation in any other clinical study.

Sponsors & Collaborators

• AVEO Pharmaceuticals, Inc.: lead

Study Sites (3)

Investigational Site 2

Scottsdale, Arizona, United States

Location

Investigational Site 3

Columbus, Ohio, United States

Location

Investigational Site 1

San Antonio, Texas, United States

Location

MeSH Terms

Conditions

Lymphoma; Multiple Myeloma; Neoplasms; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders

Interventions

ficlatuzumab; Erlotinib Hydrochloride

Condition Hierarchy (Ancestors)

Hemic and Lymphatic Diseases; Immune System Diseases; Hemostatic Disorders

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Philip Komarnitsky, MD

  AVEO Pharmaceuticals, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 28, 2008
• First Posted: July 30, 2008
• Study Start: September 1, 2008
• Primary Completion: December 1, 2010
• Study Completion: December 1, 2013
• Last Updated: January 27, 2014

Record last verified: 2014-01

Locations

US (3)