Radioimmunotherapy with 90Y-Clivatizumab Tetraxetan plus Low Dose Gemcitabine versus Placebo plus Low-Dose Gemcitabine

• Register: EUCTR
• Last refreshed on: 16 August 2016
• Main ID: EUCTR2013-004516-21-BE
• Date of registration: 26/11/2015
• Prospective Registration: No
• Primary sponsor: Immunomedics, Inc.
• Public title: Radioimmunotherapy with 90Y-Clivatizumab Tetraxetan plus Low Dose Gemcitabine versus Placebo plus Low-Dose Gemcitabine
• Scientific title: An International, Multi-Center, Double-Blind, Randomized, Phase III Trial of 90Y-Clivatuzumab Tetraxetan plus Low-Dose Gemcitabine Versus Placebo plus Low-Dose Gemcitabine in Patients with Metastatic (Stage IV) Pancreatic Adenocarcinoma Who Received at Least Two Prior Treatments (PANCRIT-1) - PANCRIT-1 (PANcreatic Cancer RadioImmunoTherapy Trial 1)
• Date of first enrolment: 02/06/2015
• Target sample size: 440
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-004516-21
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: yes Other specify the comparator: Low dose treatment with Gemcitabine Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Austria, Belgium, Canada, France, Israel, Poland, Spain, United States

Contacts

• Name: Regulatory Submissions
• Affiliation: Medpace Germany GmbH

• Name: Regulatory Submissions
• Affiliation: Medpace Germany GmbH

Key inclusion & exclusion criteria

Inclusion criteria:
1. Males or non-pregnant, non-lactating females = 18 years old, able to give signed written informed consent.
2. Histologically or cytologically confirmed adenocarcinoma of the pancreas.
3. Stage IV (metastatic) disease documented by CT imaging (MRI if patient allergic to contrast media) 90Y-clivatuzumab tetraxetan
4. Received at least two prior systemic cytotoxic chemotherapy regimens for unresectable, locally advanced or metastatic disease.
5. At least one of the prior systemic cytotoxic chemotherapy regimens for unresectable, locally advanced or metastatic disease must have contained gemcitabine and have met the following criteria:
o Completed at least one cycle of the treatment
o Received gemcitabine administered at a minimum dose of 800 mg/m2 per
week in the first cycle of treatment
o Progressed while receiving this gemcitabine regimen or within 3 months of
completing gemcitabine
o Progression was documented,
? Preferentially radiologically by tumor growth or new lesions, or by
? Clear symptomatic deterioration supported by at least two of the
following clinical criteria: = 10% worsening in KPS or = 1
worsening in ECOG; increasing weakness or fatigue; progressive
weight loss; new/worsening pain requiring increased pain
medication; new/worsening jaundice, nausea, or vomiting;
new/worsening ascites or pleural effusions; other physical or
laboratory findings consistent with disease progression.
6. Adequate performance status (Karnofsky Performance Status = 70%)
7. Expected survival = 3 months.
8. Adequate hematology without ongoing transfusional support (hemoglobin = 9g/dL, ANC = 1.5 x 10^9/L, platelets = 100 x10^9/L).
9. Adequate renal and hepatic function (creatinine and bilirubin = 1.5 X IULN;
AST and ALT = 2.5 X IULN [= 5.0 x IULN if due to liver metastases]).
10. At least 4 weeks beyond any major surgery or radiotherapy, 2 weeks beyond chemotherapy or other experimental treatments, and with any clinically significant related acute toxicities recovered at study entry to Grade 1 by NCI CTCAE v4.0.
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 147
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 293

Exclusion criteria:
1. Patients of childbearing potential sexually active but unwilling to use “double barrier” methods of birth control including male use of a condom with female use of a diaphragm, intrauterine device (IUD), or contraceptive sponge during the study until at least 4 weeks after the last dose of active study drug.
2. History of allergy or hypersensitivity or severe toxicity to any of the study drugs or their incipients
3. Known metastatic disease to the central nervous system, unless previously treated and well-controlled for at least 3 months [defined as clinically stable, no edema, no steroids and stable in 2 scans at least 4 weeks apart]
4. Presence of bulky disease (defined as any single mass > 10 cm in greatest dimension).
5. Patients with Grade = 3 nausea or vomiting, and/or signs of intestinal obstruction.
6. Rapid deterioration during screening prior to randomization, i.e. 10% decrease in KPS, 20% decrease in serum albumin levels, unstable pain symptoms requiring modifications in analgesic management, development of jaundice or symptomatic ascites.
Prior external beam irradiation to a field that includes more than 30% of the red
bone marrow.
8. Patients with non-melanoma skin cancer, cervical carcinoma in situ, superficial bladder cancer, or other non-invasive malignancy are not excluded, but patients with other prior malignancies must have had at least a 2-year disease-free interval.
9. Patients known to be HIV positive, hepatitis B positive, or hepatitis C positive.
10. Patients with:
a. Active coronary artery disease, unstable angina, myocardial infarction, or congestive heart failure present within 6 months.
b. Cardiac arrhythmia (other than stable atrial fibrillation) requiring antiarrhythmia therapy, NYHA Class II-IV disease, or prolonged QT/QTc interval.
c. Other clinically significant cardiac disease, unless baseline MUGA/2DECHO performed and LVEF is within institutional limits.
11. Moderate-to-severe (Grade = 3) respiratory illness present within 6 months.
12. Infection requiring intravenous antibiotic use within 1 week.
13. Other concurrent medical or psychiatric conditions that, in the Investigator’s
opinion, may be likely to confound study interpretation, prevent completion of
study procedures and follow-up examinations, or may cause undue risk to the patient


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

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

Metastatic (Stage IV) Pancreatic Adenocarcinoma
MedDRA version: 18.1 Level: LLT Classification code 10033605 Term: Pancreatic cancer metastatic System Organ Class: 100000004864

Intervention(s)

Product Name: 90Y-clivatuzumab tetraxetan
Product Code: 90Y-hPAM4
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: clivatizumab tetraxetan
CAS Number: 1462876-11-4
Current Sponsor code: IMMU-107
Other descriptive name: CLIVATUZUMAB TETRAXETAN
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Secondary Objective: Other measurements of overall survival (OS)
Safety
Clinical benefit (KPS, Weight, FACT-HEP, Quality of Life)
Radiologic-based measure of tumor response or progression-free survival

Main Objective: Overall Survival (OS)

Primary end point(s): Overall survival (OS), which is defined as the time from the date of randomization until the date of death from any cause.

Timepoint(s) of evaluation of this end point: any time point

Secondary Outcome(s)

Secondary end point(s): • OS at 3, 6 and 12 months
• OS in clinically important subgroups, including Karnofsky performance status (=90% vs. <90%), extent of disease at study entry, time from initial diagnosis (• Tumor response according to RECIST version 1.1, including objective response rate (the sum of complete response [CR] and partial response[PR] rates) and duration of response.
• Progression free survival (PFS).
• Clinical benefit analyses including patient weight and Karnofsky performance status.
• Quality of life analyses as assessed by the FACT-HEP questionnaire.
Safety endpoints:
• incidence and severity of adverse events,
• incidence of serious adverse events,
• safety laboratory tests (hematology and chemistry),
•vital signs,
• physical examination
• and electrocardiogram measurements.

Timepoint(s) of evaluation of this end point: At 3, 6 and 12 months

Secondary ID(s)

11380

IMMU-107-04

2013-004516-21-AT

Source(s) of Monetary Support

Immunomedics, Inc.