Safety and Efficacy Study of 90Y-hPAM4 at Different Doses

August 12, 2021 updated by: Gilead Sciences

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

Safety study to determine highest dose of 90Y-hPAM4 can be safety administered

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Actual)

21

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 <Grade 1 by NCI CTC v3.0.

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Multi Dose levels
different doses of 90YhPAM4 will be given only once.
Biological: 90Y-hPAM4
Single dose of 90Y-hPAM4 will be given and all patients will be followed for 12 weeks.
Other Names:
  • 111-IN-hPAM4
  • MUC-1 antibody

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
safety MTD
Time Frame: over the first 12 weeks, then over 2 years
over the first 12 weeks, then over 2 years

Secondary Outcome Measures

Outcome Measure
Time Frame
targeting, biodistribution, organ dosimetry
Time Frame: first 2 weeks
first 2 weeks
pharmacokinetics (PK), antigenicity,
Time Frame: first 12 weeks
first 12 weeks
efficacy
Time Frame: over first 12 weeks, then over 2 years
over first 12 weeks, then over 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Gilead Sciences

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2004

Primary Completion (Actual)

October 1, 2007

Study Completion (Actual)

October 1, 2007

Study Registration Dates

First Submitted

January 8, 2008

First Submitted That Met QC Criteria

January 8, 2008

First Posted (Estimate)

January 17, 2008

Study Record Updates

Last Update Posted (Actual)

August 19, 2021

Last Update Submitted That Met QC Criteria

August 12, 2021

Last Verified

January 1, 2008

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IM-T-hPAM4-01

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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