Phase I Trial of Weekly MEDI-522 in Patients With Refractory Solid Tumors

To determine the safety profile of single and multiple doses of MEDI522 in patients with refractory solid tumors.

Study Overview

• Status: Completed
• Conditions: Cancer
• Intervention / Treatment: Drug: MEDI-522

• Study Type: Interventional
• Enrollment: 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Villejuf, France, 94805
    • Institut Gustave Roussy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 18 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or post menopausal female patients with histologically confirmed advanced refractory solid tumors for which no reasonable therapy exists. Patient is not required to have measurable disease.
• Age >18 years
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 (see APPENDIX 1 for details).
• Patients who had prior surgery, radiation, or chemotherapy will be eligible provided at least 4 weeks have elapsed prior to study initiation. Patients must have recovered from treatment-related toxicities, and surgical wounds must be healed.
• Patients who have had prior immunotherapy with approved agents are eligible.
• Patients must have hemoglobin >10.0 g/dL, ANC >1,000/mm3, WBC >3,000/mm3,000/mm3, platelets ³100,000/mm3, bilirubin £2.0 mg/dL, AST/ALT no greater than 5 times the upper limit of normal (ULN), and serum creatinine <1.5 mg/dL (or calculated creatinine clearance ³60 mL/min).
• Patients must have prothrombin time (PT) and partial thromboplatin time (PTT) less than upper limit of normal or international normalized ratio (INR) less than 1.1.
• Patients must have thyroxine (T4) and thyroid-stimulating hormone (TSH) within normal limits.
• Patients must be informed of and understand the investigational nature of this trial and give written informed consent prior to receipt of any study medication or beginning study procedures.

Exclusion Criteria:

• Patient has known brain metastases or primary brain tumors, symptomatic pleural effusion or ascites requiring paracentesis.
• Patient has respiratory insufficiency requiring oxygen treatment, or has lymphangitic involvement of lungs.
• Patient has evidence of hematemesis, melena, hematochezia, or hematuria (2 or greater on urine dipstick).
• Patient has a history of a significant adverse event related to previously administered humanized monoclonal antibody.
• Patient has known HIV or hepatitis virus infection.
• Patient has prior myocardial infarction or angina, or uncontrolled hypertension (systolic BP >140 mm Hg).
• Patient has either prior strokes or transient ischemic attacks.
• Patient has active infections requiring systemic antiinfective therapy or other physical or psychological illnesses that would preclude drug administration or patient compliance.
• Patient has donated blood or received an investigational agent in the last 4 weeks.
• Patient has a history of active illness or behavior, including substance dependence or abuse that, in the opinion of the investigator, might pose additional risk in administering the study drug to the patient.
• General medical or psychological conditions that would not permit the patient to complete the study or sign the informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 1; MEDI-522	Drug: MEDI-522; MEDI-522 will be administered at doses of 1.0, 2.0, 4.0, 6.0, 8.0, and 10.0 mg/kg. [As a 30 minute IV infusion initially as a single dose (single-dose treatment period) and 2 to 5 weeks later as weekly doses (multiple-dose treatment period) for up to 1 year.]

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety: The incidence and severity of adverse experiences and laboratory abnormalities will be tabulated and presented overall and by dose.	Study Day 1 up to 8 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetics: Will be assessed using the variables of area under the concentration curve (AUC) which will be calculated by the trapezoidal rule, peak concentration (Cmax), time to peak concentration (Tmax), half life	35 days after the first dose
Measured pharmacokinetic parameters may be one of the factors used in determination of the Phase II regimen.	Appx. 5 days after the 4th weekly dose
Antitumor Activity: The antitumor activity of MEDI-522 in patients with refractory solid tumors will be assessed by calculating tumor response rate and time to disease progression.

Collaborators and Investigators

• Sponsor: MedImmune LLC

Study record dates

Study Major Dates

• Study Start: March 1, 2001
• Primary Completion (ACTUAL): April 1, 2002
• Study Completion (ACTUAL): June 1, 2002

Study Registration Dates

• First Submitted: December 8, 2005
• First Submitted That Met QC Criteria: December 8, 2005
• First Posted (ESTIMATE): December 9, 2005

Study Record Updates

• Last Update Posted (ESTIMATE): January 29, 2009
• Last Update Submitted That Met QC Criteria: January 28, 2009
• Last Verified: January 1, 2009

More Information

Terms related to this study

• Other Study ID Numbers: MI-CP065