Know Cancer

forgot password

A Phase I Dose-Escalation Study of BIBH-1 in Patients With Advanced or Metastatic Fibroblast Activation Protein-Positive Cancer

Phase 1
18 Years
Not Enrolling
Colorectal Cancer

Thank you

Trial Information

A Phase I Dose-Escalation Study of BIBH-1 in Patients With Advanced or Metastatic Fibroblast Activation Protein-Positive Cancer

OBJECTIVES: I. Identify the toxicity associated with increasing doses of monoclonal antibody
F19 (BIBH-1) administered weekly by intravenous infusion in patients with unresectable,
advanced or metastatic fibroblast activation protein-positive colorectal cancer. II.
Determine the dose limiting toxicity and maximum tolerated dose of this drug in these
patients. III. Measure induction titers of human anti-human antibody to BIBH-1 and correlate
immunologic-related clinical effects. IV. Determine the pharmacokinetics, biodistribution,
and imaging characteristics of increasing intravenous doses of the drug. V. Document tumor
responses in this patient population.

OUTLINE: This is a dose escalation, open label, multicenter study. Patients receive
monoclonal antibody F19 (BIBH-1) IV over 60 minutes weekly for 12 weeks. The first, fifth,
and ninth treatments are combined with iodine I 131. Patients with stable or responding
disease may continue treatment for up to 12 months. The dose of BIBH-1 is escalated in
cohorts of 3-6 patients until the maximum tolerated dose (MTD) is determined. The MTD is
defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose
limiting toxicity. Patients are followed at 1 month.

PROJECTED ACCRUAL: A maximum of 24 patients will be accrued for this study within 8 months.

Inclusion Criteria

DISEASE CHARACTERISTICS: Histologically confirmed unresectable, advanced and/or metastatic
disease: Colorectal cancer Measurable or evaluable disease Epidemiologically proven
fibroblast activation protein positive Failed or refused conventional treatment, and
unlikely to derive significant benefit from conventional treatments No active CNS
metastases No new or progressive lesions on CT scan, more than 3 months since treatment
(i.e., surgery or radiotherapy) for brain metastases, and/or not receiving mitomycin
Hormone receptor status: Not specified

PATIENT CHARACTERISTICS: Age: 18 and over Menopausal status: Not specified Performance
status: Karnofsky 70-100% Life expectancy: At least 4 months Hematopoietic: Absolute
granulocyte count at least 1,500/mm3 Platelet count at least 100,000/mm3 Hepatic: ALT/AST
no greater than 3 times upper limit of normal Bilirubin less than 2 mg/dL Renal:
Creatinine no greater than 2.0 mg/dL Other: Not pregnant or nursing Fertile patients must
use effective contraception No other serious illness No active infections requiring
antibiotics No bleeding disorders No other diseases that may potentially interfere with
obtaining accurate study results

PRIOR CONCURRENT THERAPY: Biologic therapy: At least 4 weeks since prior immunotherapy No
prior murine, chimeric or humanized antibody and/or antibody fragment Chemotherapy: See
Disease Characteristics At least 4 weeks since prior chemotherapy (6 weeks for
nitrosoureas and mitomycin) Endocrine therapy: No concurrent systemic corticosteroids
(except for acute management of allergic-type events) No concurrent immunosuppressive
agents Radiotherapy: See Disease Characteristics Surgery: See Disease Characteristics
Recovered from surgery Other: At least 4 weeks since other prior investigational agents

Type of Study:


Study Design:

Primary Purpose: Treatment

Principal Investigator

Sydney Welt, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Memorial Sloan-Kettering Cancer Center


United States: Federal Government

Study ID:




Start Date:

November 1998

Completion Date:

Related Keywords:

  • Colorectal Cancer
  • stage III colon cancer
  • stage IV colon cancer
  • stage III rectal cancer
  • stage IV rectal cancer
  • recurrent colon cancer
  • recurrent rectal cancer
  • Colorectal Neoplasms



Memorial Sloan-Kettering Cancer Center New York, New York  10021
Mayo Clinic Cancer Center Rochester, Minnesota  55905