A Phase Ib/II Study of Fractionated 90-Y-hPAM4 Plus Gemcitabine in Patients with Previously Untreated Advanced Pancreatic Cancer

• Register: EUCTR
• Last refreshed on: 19 November 2012
• Main ID: EUCTR2008-003993-16-DE
• Date of registration: 11/08/2008
• Prospective Registration: Yes
• Primary sponsor: Immunomedics, Inc.
• Public title: A Phase Ib/II Study of Fractionated 90-Y-hPAM4 Plus Gemcitabine in Patients with Previously Untreated Advanced Pancreatic Cancer
• Scientific title: A Phase Ib/II Study of Fractionated 90-Y-hPAM4 Plus Gemcitabine in Patients with Previously Untreated Advanced Pancreatic Cancer
• Date of first enrolment: 03/04/2009
• Target sample size: 20
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-003993-16
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: no Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: Placebo: Other:

Countries of recruitment

Germany

Key inclusion & exclusion criteria

Inclusion criteria:
• Male or female patients, >18 years of age, who are able to understand and give written informed consent.
• Histologically or cytologically confirmed pancreatic adenocarcinoma.
• Stage III (locally advanced, unresectable) or Stage IV (metastatic) disease, including patients who underwent surgery but had incomplete resections.
• Treatment naïve (no prior chemotherapy, radiotherapy or investigational agents for pancreatic cancer)
• Karnofsky performance status > 70 % (Appendix A).
• Expected survival > 3 months.
• At least 4 weeks beyond major surgery 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 > 11 g/dL, ANC > 2,000 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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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 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 or prevent completion of study procedures and follow-up examinations.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

This is a phase Ib, open-label, dose exploration study of 90-Y-hPAM4 administered as one or more treatment cycles of fractionated radioimmunotherapy in combination with radiosensitizing gemcitabine as front line therapy for patients with Stage III (unresectable locally advanced) or Stage IV (metastatic) pancreatic cancer, including patients who may have undergone surgery bu had incomplete resections.
MedDRA version: 9.1 Level: LLT Classification code 10033605 Term: Pancreatic cancer metastatic
MedDRA version: 9.1 Level: LLT Classification code 10033606 Term: Pancreatic cancer non-resectable

Intervention(s)

Product Name: hPAM4
Product Code: IMMU-107
Pharmaceutical Form: Intravenous infusion
CAS Number: 943976-23-6
Current Sponsor code: IMMU-107
Other descriptive name: hPAM4
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Primary Outcome(s)

Primary end point(s): A composite endpoint evaluating the time to treatment failure (TTTF, as measured from the start of treatment to the initiation of other therapy for pancreatic cancer, disease progression, death or last follow-up, whichever is earliest) will be summarized using Kaplan-Meier product-limit method.

All patients who receive any dose of 111In-or 90Y-hPAM4 will be included in the safety analyses. In general, safety will be summarized by dose level.

Secondary Objective: Include the assessment of tumor targeting, biodistribution, organ dosimetry and pharmacokinetics (PK) of 90-Y-hPAM4 as determined by pre-therapy administration of 111-In-hPAM4, the assessment of the antigenicity of 90-Y-hPAM4, as determined by development of HAHA, and to obtain preliminary information on the efficacy of fractionated 90-Y-hPAM4 with gemcitabine treatment regimen, as determined by CT and/or PET/CT imaging, conversion to surgically resectability, initiation of other treatments, and survival.; clinical benefit as determined by quality of life and pain assessments

Main Objective: To evaluate the feasibility, safety and tolerability of this treatment regimen, and to determine acceptable 90-Y dose and gemcitabine dosing for use with this approach.

Secondary ID(s)

IM-T-hPAM4-02