Phase I Study of MEDI522 in Patients With Irinotecan-Refractory Advanced Colorectal Cancer

This study has been completed.
Sponsor:
Information provided by:
MedImmune LLC
ClinicalTrials.gov Identifier:
NCT00284817
First received: January 31, 2006
Last updated: May 27, 2008
Last verified: May 2008
  Purpose

- Assess the safety and tolerance of a weekly MEDI522 regimen in patients with irinotecan-refractory advanced CRC or other solid tumors refractory to standard therapy.


Condition Intervention Phase
Cancer
Drug: MEDI-522
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study of MEDI522, a Humanized Monoclonal Antibody Directed Against the Human Alpha V Beta 3 Integrin, in Patients With Irinotecan-Refractory Advanced Colorectal Cancer or Other Solid Tumors Refractory to Standard Therapy

Resource links provided by NLM:


Further study details as provided by MedImmune LLC:

Primary Outcome Measures:
  • The recommended Phase II dose will be based on acceptable dose-limiting toxicity [ Time Frame: Study Days 0, 7, 14, 21, 28, 35, 42, and 49. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Pharmacokinetic parameters may also be factored into the determination of a Phase II dose and; Tumor response [ Time Frame: Study Days 0, 28, 56, 84, 112, 140, 168, 196, 224, 252, 280, 308, 336, 357; and tumor response on Study Days 56, 112, 168, 224, 280, 336, and 387. ] [ Designated as safety issue: No ]

Enrollment: 17
Study Start Date: July 2001
Study Completion Date: May 2005
Primary Completion Date: January 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
MEDI-522
Drug: MEDI-522
Administered as a 30-minute IV infusion; 4 mg/kg on Study Day 0 followed by weekly maintenance doses of 1 mg/kg for 51 weeks.
Experimental: 2
MEDI-522
Drug: MEDI-522
Administered as a 30-minute IV infusion; 4 mg/kg on Study Day 0 followed by weekly maintenance doses of 2mg/kg for 51 weeks.
Experimental: 3
MEDI-522
Drug: MEDI-522
Administered as a 30-minute IV infusion; 6 mg/kg on Study Day 0 followed by weekly maintenance doses of 2mg/kg for 51 weeks.
Experimental: 4
MEDI-522
Drug: MEDI-522
Administered as a 30-minute IV infusion; on Study Day 0 followed by weekly maintenance doses of 3mg/kg for 51 weeks.
Experimental: 5
MEDI-522
Drug: MEDI-522
The next cohort of patients will be treated after at least 3 of 4 patients treated in the previous cohort receive at least 3 weeks of treatment and experience no dose-limiting toxicity (DLT).

Detailed Description:
  • Assess the safety and tolerance of a weekly MEDI 522 regimen in patients with irinotecan-refractory advanced CRC.
  • Determine a Phase II recommended dose based on acceptable dose-limiting toxicity. Other considerations such as pharmacokinetic parameters may also be factored into the determination of a Phase II dose.

The secondary objectives of the study are to:

  • Assess any antitumor activity of MEDI-522 in this patient population.
  Eligibility

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

Inclusion Criteria:

  • Patients must have histologically-confirmed advanced CRC that has progressed through an irinotecan-containing regimen for metastatic disease, or has recurred during, or within 6 months of completing, an irinotecan-containing adjuvant regimen, or other histologically-confirmed solid tumors refractory to standard therapy.
  • Age at least 18 years at the time of the first dose of study drug.
  • Both males and females are eligible. Sexually active females, unless surgically sterile (or at least one year post-menopausal), must have used an effective method of avoiding pregnancy (including oral or implanted contraceptives, IUD, female condom, diaphragm with spermicide, cervical cap, abstinence, use of a condom by the sexual partner or sterile sexual partner) for 30 days prior to the first dose of study drug, and must agree to continue using such precautions for 30 days after the final dose of study drug. Sexually active females of reproductive potential must have a negative serum b human chorionic gonadotropin (bhCG) pregnancy test within 3 days of start of therapy.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. ECOG criteria are described in Appendix A.
  • Patients who had prior treatment with chemotherapy or radiotherapy or had prior surgery are eligible for study entry if at least 4 weeks have past since their treatment/surgery.
  • All toxicities related to prior treatment must have resolved and all surgical wounds must have healed.
  • Prior immunotherapy with approved agents is allowable.
  • ANC ³1500/mm3, platelets ³100,000/mm3, hemoglobin >10.0 g/dL, serum creatinine £1.5 mg/dL or calculated creatinine clearance >50 mL/min, serum bilirubin £2.0 mg/dL, and AST/ALT £5 times the upper limit of normal (ULN).
  • PT/PTT less than ULN or international normalized ratio (INR) less than 1.12.
  • Thyroxine (T4) and thyroid-stimulating hormone (TSH) within normal limits.
  • Written informed consent obtained from the patient prior to receipt of any study medication or beginning study procedures.

Exclusion Criteria:

  • Pregnancy or nursing.
  • Known brain metastases or primary brain tumors, symptomatic pleural effusion or ascites requiring paracentesis.
  • Respiratory insufficiency requiring oxygen treatment, or lymphangitic involvement of lungs.
  • Any evidence of hematemesis, melena, hematochezia, or gross hematuria.
  • A history of significant adverse events related to a previously administered humanized monoclonal antibody.
  • A known human immunodeficiency virus (HIV) or hepatitis virus infection.
  • A prior myocardial infarction or angina, or uncontrolled hypertension (systolic blood pressure >150 mm Hg).
  • A prior stroke or transient ischemic attack.
  • An active infection requiring systemic antiinfective therapy.
  • Received an investigational agent in the last 4 weeks of initiation of study treatment.
  • A requirement for palliative chemotherapy, hormonal therapy, or immunotherapy during the course of the study.
  • Clinical evidence of bowel obstruction.
  • A history of other malignancies within the past 5 years (with the exception of basal cell carcinoma of the skin or completely excised in situ carcinoma of the cervix).
  • A general medical or psychological condition or behavior, including substance dependence or abuse that, in the opinion of the investigator, might not permit the patient to complete the study or sign the informed consent.
  • Prior treatment with MEDI-522 or MEDI-523.
  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: NCT00284817

Locations
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10021
Sponsors and Collaborators
MedImmune LLC
Investigators
Study Director: Krista Arbaugh, Dir., Clinical Ops MedImmune LLC
  More Information

No publications provided

Responsible Party: Luz Hammershaimb, M.D., V.P., Clinical Dev., MedImmune LLC
ClinicalTrials.gov Identifier: NCT00284817     History of Changes
Other Study ID Numbers: MI-CP068
Study First Received: January 31, 2006
Last Updated: May 27, 2008
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Irinotecan
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 20, 2014