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A Phase I, Dose-Escalating Study to Investigate the Safety, Tolerability, Pharmacokinetics and Dosimetry of a Single Dose of 90YHumanized PAM4 IgG in Patients With Locally Advanced/Metastatic Pancreatic Cancer


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

Thank you

Trial Information

A Phase I, Dose-Escalating Study to Investigate the Safety, Tolerability, Pharmacokinetics and Dosimetry of a Single Dose of 90YHumanized PAM4 IgG in Patients With Locally Advanced/Metastatic Pancreatic Cancer


radiolabeled anti-MUC1 humanized antibody) administered intravenously as a single dose to
patients with locally advanced and/or metastatic pancreatic cancer. The primary objective is
to determine the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of 90Y-hPAM4
in this population. Secondary objectives include the assessment of tumor targeting,
biodistribution, organ dosimetry and pharmacokinetics (PK) of 90Y-hPAM4 as determined by
pre-therapy administration of 111In-hPAM4, the assessment of the antigenicity of 90Y-hPAM4,
as determined by development of human anti-humanized antibodies (HAHA), and to obtain
preliminary information on the efficacy of single dose 90Y-hPAM4 in this patient population.


Inclusion Criteria:



- Male or female patients, >18 years of age, who are able to understand and give
written informed consent.

- Histologically or cytologically confirmed, Stage III or IV pancreatic adenocarcinoma.

- Patients with Stage III (locally advanced) disease must have documented progression
after failing primary therapy

- Patients with Stage IV (metastatic) disease must not have received more than one
chemotherapy regimen.

- Measurable disease by CT, with at least on lesion >1.5 cm in one dimension.

- Karnofsky performance status > 70 % (Appendix A).

- Expected survival > three months.

- At least 4 weeks beyond chemotherapy, radiotherapy, major surgery, other experimental
treatments, and recovered from all acute toxicities.

- At least 2 weeks beyond corticosteroids, except low doses (i.e., 20 mg/day of
prednisone or equivalent) to treat nausea or other illness such as rheumatoid
arthritis

- Adequate hematology without ongoing transfusional support (hemoglobin > 10 g/dL, ANC
> 1,500 per mm3, platelets > 150,000 per mm3)

- Adequate renal and hepatic function (creatinine and bilirubin ≤ 1.5 X IULN, AST and
ALT ≤ 2.0 X IULN)

- Otherwise, all toxicity at study entry
Exclusion Criteria:

- Women who are pregnant or lactating.

- Women of childbearing potential and fertile men unwilling to use effective
contraception during study until conclusion of 12-week post-treatment evaluation
period.

- Known metastatic disease to the central nervous system.

- Presence of bulky disease (defined as any single mass >10 cm in its greatest
dimension)

- Patients with >Grade 2 anorexia, nausea or vomiting, and/or signs of intestinal
obstruction.

- Prior treatment with nitrosureas, actinomycin-D, radioimmunotherapy or other
antibody-based therapies (murine, chimeric, humanized or human) Prior radiation dose
>3,000 cGy to the liver, >2,000 cGy to lungs and kidneys or prior external beam
irradiation to a field that includes more than 30% of the red marrow.

- Patients with non-melanoma skin cancer or carcinoma in situ of the cervix are not
excluded, but patients with other prior malignancies must have had at least a 5- year
disease free interval.

- Patients known to be HIV positive, hepatitis B positive, or hepatitis C positive.

- Known history of active coronary artery disease, unstable angina, myocardial
infarction, or congestive heart failure present within 6 months or cardiac arrhythmia
requiring anti-arrhythmia therapy.

- Known history of active COPD, or other moderate-to-severe respiratory illness present
within 6 months.

- Known autoimmune disease or presence of autoimmune phenomena (except rheumatoid
arthritis requiring only low dose maintenance corticosteroids).

- Infection requiring intravenous antibiotic use within 1 week.

- Other concurrent medical or psychiatric conditions that, in the Investigator's
opinion, may be likely to confound study interpretation

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

safety MTD

Outcome Time Frame:

over the first 12 weeks, then over 2 years

Safety Issue:

Yes

Principal Investigator

William Wegener, MD, PhD

Investigator Role:

Study Chair

Investigator Affiliation:

Immunomedics, Inc.

Authority:

United States: Food and Drug Administration

Study ID:

IM-T-hPAM4-01

NCT ID:

NCT00597129

Start Date:

August 2004

Completion Date:

October 2007

Related Keywords:

  • Pancreatic Cancer
  • pancreatic cancer
  • cancer of the pancreas
  • pancreas cancer
  • Pancreatic Neoplasms

Name

Location

Fox Chase Cancer Center Philadelphia, Pennsylvania  19111
Nebraska Medical Center Omaha, Nebraska  68198
Goshen Cancer Center Goshen, Indiana  46526
University of Medicine and Dentistry Newark, New Jersey  07101