Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

Yttrium Y 90 DOTA Monoclonal Antibody HuPAM4 in Treating Patients With Stage III or Stage IV Pancreatic Cancer

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase I Treatment Active 18 and over Pharmaceutical / Industry IM-T-HPAM4-01 UMDNJ-0120020277, NCT00303680

Objectives

Primary

1. Determine the dose-limiting toxicity and maximum tolerated dose of yttrium Y 90 DOTA monoclonal antibody HuPAM4 (Y90 DOTA MOAB HuPAM4) in patients with stage III or IV pancreatic adenocarcinoma.

Secondary

1. Determine tumor targeting, biodistribution, organ dosimetry, and pharmacokinetics of this drug by administering indium In 111 DOTA monoclonal antibody HuPAM4 to these patients.
2. Determine the pharmacokinetics of unconjugated monoclonal antibody HuPAM4, based on ELISA measurements of serum antibody levels, in these patients.
3. Determine the antigenicity of Y90 DOTA MOAB HuPAM4, in terms of development of human anti-humanized antibodies, in these patients.
4. Determine, preliminarily, the efficacy of this drug in these patients.

Entry Criteria

Disease Characteristics:

• Histologically or cytologically confirmed pancreatic adenocarcinoma
  • Stage III disease
    • Documented disease progression after failing prior primary therapy
  • Stage IV disease



• Not a candidate for potentially curative resection



• Measurable disease
  • At least 1 unidimensionally measurable lesion > 1.5 cm by CT scan



• No bulky disease, defined as any single mass > 10 cm in its greatest dimension



• No known CNS metastases

Prior/Concurrent Therapy:

Biologic therapy

• See Radiotherapy
• More than 4 weeks since prior biologic therapy
• No prior antibody-based therapies (i.e., murine, chimeric, humanized, or human antibodies)
• No concurrent prophylactic sargramostim (GM-CSF) or filgrastim (G-CSF)
• No other concurrent biologic therapy*

Chemotherapy

• No more than 1 prior chemotherapy regimen for stage IV disease
• More than 4 weeks since other prior chemotherapy
• No prior nitrosoureas or dactinomycin
• No concurrent chemotherapy*

Endocrine therapy

• More than 2 weeks since prior corticosteroids, except low-dose steroids (i.e., 20 mg/day of prednisone or equivalent) to treat nausea or other illnesses, such as rheumatoid arthritis
• No concurrent corticosteroids, except if medically necessary
  • Concurrent low-dose steroids (i.e., 20 mg/day of prednisone or equivalent) for nausea or as maintenance therapy for other illnesses, such as rheumatoid arthritis allowed

Radiotherapy

• More than 4 weeks since prior radiotherapy
• No prior radioimmunotherapy
• No prior external-beam radiotherapy to > 30% of the red marrow
• No prior radiotherapy dose > 3,000 cGy to the liver
• No prior radiotherapy dose > 2,000 cGy to the lungs and kidneys
• No prior radiotherapy at a maximal tolerable level to any organ
• No concurrent radiotherapy*

Surgery

• More than 4 weeks since prior major surgery
• No concurrent major surgery*

Other

• Recovered from all prior therapy (toxicity ≤ grade 1)
• More than 4 weeks since prior experimental treatment (i.e., drugs or procedures)
• No other concurrent experimental treatment*

 [Note: *Except for patients who progress at the 4- or 8-week study assessment; further treatment may be administered at the discretion of the managing physician]

Patient Characteristics:

Age

• 18 and over

Performance status

• Karnofsky 70-100%

Life expectancy

• At least 3 months

Hematopoietic

• Hemoglobin ≥ 10 g/dL*
• Absolute neutrophil count ≥ 1,500/mm³*
• Platelet count ≥ 150,000/mm³*

 [Note: *No ongoing transfusion support]

Hepatic

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST and ALT ≤ 2.0 times ULN
• No known hepatitis B or C positivity

Renal

• Creatinine ≤ 1.5 times ULN

Cardiovascular

• No active coronary artery disease within the past 6 months
• No unstable angina within the past 6 months
• No myocardial infarction within the past 6 months
• No congestive heart failure within the past 6 months
• No cardiac arrhythmia requiring anti-arrhythmia therapy

Pulmonary

• No active chronic obstructive pulmonary disease within the past 6 months
• No other moderate-to-severe respiratory illness within the past 6 months

Gastrointestinal

• No anorexia > grade 2
• No nausea or vomiting
• No signs of intestinal obstruction

Immunologic

• No known HIV positivity
• No autoimmune disease or autoimmune phenomena
  • Rheumatoid arthritis requiring only low-dose maintenance corticosteroids allowed
• No infection requiring IV antibiotics within the past week

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 12 weeks after study treatment
• No other malignancy within the past 5 years except nonmelanoma skin cancer or carcinoma in situ of the cervix
• No other medical or psychiatric condition that would preclude study participation

Expected Enrollment

Approximately 28-40 patients will be accrued for this study.

Outline

This is a nonrandomized, open-label, dose-escalation study of yttrium Y 90 DOTA monoclonal antibody HuPAM4 (Y90 DOTA MOAB HuPAM4).

Patients receive unconjugated monoclonal antibody HuPAM4 IV over 30-60 minutes followed by indium In 111 DOTA monoclonal antibody HuPAM4 IV over 30-60 minutes. Patients then undergo imaging and blood sampling over 1 week to evaluate tumor targeting, biodistribution, and organ dosimetry. Approximately 1 week later, patients with adequate biodistribution, definitive tumor targeting, and acceptable organ dosimetry receive unconjugated monoclonal antibody HuPAM4 IV over 30-60 minutes followed by Y90 DOTA MOAB HuPAM4 IV over 30-60 minutes.

Cohorts of 3-6 patients receive escalating doses of Y90 DOTA MOAB HuPAM4 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. Up to 10 additional patients (total of 16) are treated at the MTD.

Patients who do not receive Y90 DOTA MOAB HuPAM4 are followed at weeks 1, 4, 8, and 12 and then monthly for at least 6 months. After completion of study treatment, all other patients are followed periodically for 5 years.

Trial Contact Information

Trial Lead Organizations

Immunomedics, Incorporated

William Wegener, MD, PhD, Protocol chair		Ph: 973-605-8200

U.S.A.
Indiana
	Goshen
	Center for Cancer Care at Goshen General Hospital
		Clinical Trials Office - Center for Cancer Care at Goshen General Hospital	Ph:  574-535-2858
New Jersey
	Newark
	UMDNJ University Hospital
		Moumita Chakraborty	Ph:  973-972-7889
Pennsylvania
	Philadelphia
	Fox Chase Cancer Center - Philadelphia
		Clinical Trials Office - Fox Chase Cancer Center - Philadelphia	Ph:  215-728-4790

Registry Information
Official Title		A Phase I, Dose-Escalating Study to Investigate the Safety, Tolerability, Pharmacokinetics and Dosimetry of a Single Dose of 90Y-Humanized PAM4 IgG in Patients With Locally Advanced/Metastatic Pancreatic Cancer
Trial Start Date		2004-08-23
Registered in ClinicalTrials.gov		NCT00303680
Date Submitted to PDQ		2005-02-03
Information Last Verified		2007-05-13