E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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 Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10033605 |
E.1.2 | Term | Pancreatic cancer metastatic |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10033606 |
E.1.2 | Term | Pancreatic cancer non-resectable |
|
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
|
E.2.2 | Secondary objectives of the trial |
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 |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 <Grade 1 by NCI CTC v3.0.
|
|
E.4 | Principal 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.
|
|
E.5 End points |
E.5.1 | 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. |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
the last visit of the last subject undergoing the trial |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |