Know Cancer

or
forgot password

Phase I/II Study of MEDI-522, A Humanized Monoclonal Antibody Directed Against the Human Alpha V Beta 3 Integrin, in Patients With Irinotecan-Refractory Advanced Colorectal Cancer


Phase 1/Phase 2
18 Years
N/A
Not Enrolling
Both
Colorectal Cancer

Thank you

Trial Information

Phase I/II Study of MEDI-522, A Humanized Monoclonal Antibody Directed Against the Human Alpha V Beta 3 Integrin, in Patients With Irinotecan-Refractory Advanced Colorectal Cancer


OBJECTIVES:

- Determine the recommended phase II dose of monoclonal antibody anti-anb3 integrin in
patients with irinotecan-refractory advanced colorectal cancer.

- Determine the safety and tolerance of this drug in these patients.

- Determine any antitumor activity of this drug in these patients.

- Determine the objective response rate, response duration, and time to progression in
patients treated with this drug.

- Determine the pharmacokinetics of this drug in these patients.

OUTLINE: This is a dose-escalation study.

Patients receive monoclonal antibody anti-anb3 integrin IV over 30 minutes once weekly on
weeks 1-52 in the absence of disease progression or unacceptable toxicity. Patients with
responding disease may continue therapy.

Cohort of 4-6 patients receive escalating doses of monoclonal antibody anti-anb3 integrin
until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose
preceding that at which 2 of 4 or 6 patients experience dose-limiting toxicity. Once the MTD
is determined, additional patients are treated at that dose in the phase II portion of the
study.

Patients are followed every 3 months for 2 years.

PROJECTED ACCRUAL: A total of 4-24 patients will be accrued for phase I of this study and a
total of 40 patients will be accrued for phase II of this study.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Histologically confirmed advanced colorectal cancer

- Disease progression while receiving an irinotecan-containing regimen for metastatic
colorectal cancer OR

- Disease recurrence within 6 months after completing an irinotecan-containing regimen
in the adjuvant setting

- At least 1 measurable lesion (for phase II only)

- At least 20 mm by x-ray, CT scan, MRI, or photograph

- Recurrent disease after surgery or radiotherapy is considered measurable if it
has been at least 4 weeks since treatment and measurable disease is outside the
port of prior radiotherapy or there is evidence of disease progression within
the port of prior radiotherapy

- The following are not considered measurable:

- Pleural effusion

- Ascites

- Osteoblastic lesion or evidence of disease on bone scan alone

- Progressive irradiated lesions alone

- Bone marrow involvement

- Brain metastases

- Malignant hepatomegaly by physical exam alone

- Chemical markers (e.g., carcinoembryonic antigen)

- No known brain metastases or primary brain tumors

- No symptomatic pleural effusion or ascites requiring paracentesis

- No clinical evidence of bowel obstruction

PATIENT CHARACTERISTICS:

Age:

- 18 and over

Performance status:

- ECOG 0-1

Life expectancy:

- Not specified

Hematopoietic:

- Absolute neutrophil count at least 1,500/mm^3

- Platelet count at least 100,000/mm^3

- Hemoglobin greater than 10.0 g/dL

Hepatic:

- Bilirubin no greater than 2.0 mg/dL

- AST/ALT no greater than 5 times upper limit of normal (ULN)

- PT/PTT less than ULN OR

- INR less than 1.12

- No hepatitis virus infection

Renal:

- Creatinine no greater than 1.5 mg/dL OR

- Creatinine clearance greater than 50 mL/min

Cardiovascular:

- No prior myocardial infarction

- No angina

- No uncontrolled hypertension (systolic blood pressure greater than 150 mm Hg)

- No prior cerebrovascular accident or transient ischemic attack

Pulmonary:

- No respiratory insufficiency requiring oxygen treatment

- No lymphangitic involvement of lungs

Other:

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception for 30 days before, during, and for
30 days after study

- Thyroxine and thyroid-stimulating hormone normal

- No hematemesis, melena, hematochezia, or gross hematuria

- No prior significant adverse reaction to a humanized monoclonal antibody

- No known HIV infection

- No active infection requiring systemic anti-infective therapy

- No other medical or psychological condition or behavior, including substance
dependence or abuse, that would preclude study

- No other malignancy within the past 5 years except basal cell skin cancer or
completely excised carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- Prior immunotherapy with approved agents allowed

- No prior monoclonal antibody anti-anb3 integrin or its precursor (MEDI-523)

- No other concurrent immunotherapy

Chemotherapy:

- See Disease Characteristics

- At least 4 weeks since prior chemotherapy

- No concurrent palliative chemotherapy

Endocrine therapy:

- No concurrent hormonal therapy

Radiotherapy:

- See Disease Characteristics

- At least 4 weeks since prior radiotherapy

Surgery:

- See Disease Characteristics

- At least 4 weeks since prior surgery and surgical wounds must have healed

Other:

- Recovered from all prior therapy

- At least 4 weeks since prior investigational agents

Type of Study:

Interventional

Study Design:

Primary Purpose: Treatment

Principal Investigator

Leonard B. Saltz, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Memorial Sloan-Kettering Cancer Center

Authority:

United States: Federal Government

Study ID:

01-078

NCT ID:

NCT00027729

Start Date:

June 2001

Completion Date:

November 2004

Related Keywords:

  • Colorectal Cancer
  • recurrent colon cancer
  • recurrent rectal cancer
  • Colorectal Neoplasms

Name

Location

Memorial Sloan-Kettering Cancer CenterNew York, New York  10021