Phase II Study of Coagulation Factor VIIa Inhibitor PCI-27483 in Pancreatic Cancer Patients Receiving Treatment With Gemcitabine
Overview
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Pharmacyclics LLC.
- Enrollment
- 42
- Locations
- 17
- Primary Endpoint
- Number of Participants With Treatment Emergent Adverse Events (AEs)
Overview
Brief Summary
The purpose of this study is to evaluate the safety and tolerability of selected dose 1.2mg/kg BID dosage administered subcutaneously (SC) administered PCI-27483 to metastatic or locally advanced pancreatic cancer patients receiving concurrent therapy with intravenously administered gemcitabine for 12 weeks.
Detailed Description
This study will be conducted in three segments: Part A, Part B and Part C. Parts A and B are 12 weeks of treatment followed by 4 weeks of evaluation. In part A patients will dose-escalate up to three dose levels of PCI-27483 administered as subcutaneous (SC) injections twice-daily (BID). Part B to start once 4th patient completes 90 of 112 doses in 8 weeks. In part B patients are randomized to PCI-27483 and gemcitabine (active arm) OR gemcitabine only (control arm). PCI-27483 doses in both Part A and B will be administered in combination with a standard regimen of gemcitabine. Patients with a tumor response or stable disease at 12 weeks will have the opportunity to continue PCI-27483 treatment until disease progression or the Investigator considers the study treatment to be no longer tolerable. Treatment with gemcitabine in either the active or control arm may continue until a standard course of gemcitabine therapy has been completed. Patients will complete Part A or Part B after 16 weeks on study regardless of treatment duration. Evaluable patients will roll over into part C and be followed for 12 months from enrollment (first dose).
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Men or women at least 18 years old
- •Body weight ≥ 40 and ≤ 100 kg.
- •Part A: Metastatic ductal adenocarcinoma of the pancreas diagnosed ≤ 4 months prior to enrollment. (Locally advanced does not have any criteria)
- •Part B: Locally advanced ductal adenocarcinoma of the pancreas diagnosed ≤ 3 months prior to enrollment or metastatic ductal adenocarcinoma diagnosed ≤ 2 months.
- •Measurable disease by spiral CT scan (SCT) in accordance with RECIST criteria.
- •Patients after non-curative surgery are eligible if at least 4 weeks after surgery and recovered from significant surgical morbidity.
- •Estimated life expectancy of at least 4 months.
- •ECOG performance status 0 to
- •Normal baseline coagulation function as defined by:
- •PT 10-16 seconds, and
Exclusion Criteria
- •History of any clinically significant medical condition that, in the opinion of the Principal Investigator, would interfere with the study evaluation or interpretation.
- •Known history of brain metastases.
- •Any evidence of intra-cranial hemorrhage based on head CT scan within 30 days of enrollment.
- •History of disease progression while being treated with gemcitabine.
- •Radiotherapy of the primary tumor or unwillingness to defer radiotherapy of the primary tumor until \> 3 months from initiation of treatment.
- •History of venous thromboembolism (eg, deep vein thrombosis, pulmonary embolism,and arterial thromboembolism) or other indications for anticoagulant treatment (eg,mechanical heart values, atrial fibrillation, etc.) within the last year. Local thrombus in the mesenteric or portal vein is acceptable.
- •Uncontrolled hypertension (systolic \> 160 or diastolic \> 100 mm Hg on medical treatment).
- •Continued anticoagulation therapy or anticoagulation therapy within 2 months prior to enrollment, except for perisurgical prophylaxis which must have ceased 2 weeks before enrollment.
- •Contraindication to systemic anticoagulation.
- •Continued treatment with antiplatelet drugs including aspirin, clopidogrel, etc. within the past 72 hours.
Arms & Interventions
Gemcitabine
Subjects receive Gemcitabine 1000 mg/m2 weekly intravenous infusion.
Intervention: Gemcitabine (Drug)
PCI-27483 + Gemcitabine
Part A: Subjects received PCI-27483 0.8 mg/kg BID as initial dose and may be escalated to 1.2, and 1.5 mg/kg BID. At the same time, subjects received Gemcitabine 1000 mg/m2 weekly intravenous infusion.
Part B: Subjects received the PCI-27483 at 1.2 mg/kg BID and Gemcitabine 1000 mg/m2 weekly intravenous infusion.
Intervention: PCI-27483 (Drug)
PCI-27483 + Gemcitabine
Part A: Subjects received PCI-27483 0.8 mg/kg BID as initial dose and may be escalated to 1.2, and 1.5 mg/kg BID. At the same time, subjects received Gemcitabine 1000 mg/m2 weekly intravenous infusion.
Part B: Subjects received the PCI-27483 at 1.2 mg/kg BID and Gemcitabine 1000 mg/m2 weekly intravenous infusion.
Intervention: Gemcitabine (Drug)
Outcomes
Primary Outcomes
Number of Participants With Treatment Emergent Adverse Events (AEs)
Time Frame: First dose until 28 days after last dose of PCI-27483 or gemcitabine whichever occurs last in the assigned part (A or B).
Clinically meaningful toxicity adverse events will be defined in accordance with by CTCAE v3.0
Secondary Outcomes
No secondary outcomes reported