A Phase III Study of BBI-608 plus nab-Paclitaxel with Gemcitabine in Adult Patients with Metastatic Pancreatic Adenocarcinoma.
- Conditions
- Metastatic Pancreatic Ductal Adenocarcinoma (PDAC)10027476
- Registration Number
- NL-OMON50631
- Lead Sponsor
- Sumitomo Dainippon Pharma Oncology, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 4
Patients must fulfill all of the following criteria to be eligible for
admission to the study:, 4.1.1. Written, signed consent for trial participation
must be obtained from the patient appropriately in accordance with applicable
ICH guidelines and local and regulatory requirements prior to the performance
of any study specific procedure., 4.1.2. Must have histologically or
cytologically confirmed advanced PDAC that is metastatic. The definitive
diagnosis of metastatic PDAC will be made by integrating the histopathological
data within the context of the clinical and radiographic data. Patients with
islet cell neoplasms are excluded., 4.1.3. Must not have previously received
chemotherapy or any investigational agent for the treatment of PDAC.
* A fluoropyrimidine or gemcitabine administered as a radiation sensitizer in
the adjuvant setting is allowed for as long as last dose was administered > 6
months prior to randomization and no lingering toxicities are present., 4.1.4.
Nab-paclitaxel with gemcitabine therapy is appropriate for the patient and
recommended by the Investigator., 4.1.5. Patient has one or more metastatic
tumors evaluable by CT scan with contrast (or MRI, if patient is allergic to CT
contrast media) per RECIST 1.1. Imaging investigations including CT/MRI of
chest/abdomen/pelvis or other scans as necessary to document all sites of
disease must be performed within 14 days prior to randomization. Qualifying
scans performed as part of standard of care prior to patient signature of the
study informed consent will be acceptable as baseline scanning as long as
scanning is performed < 14 days prior to randomization., 4.1.6. Must have ECOG
Performance Status of 0 or 1, assessed within 14 days prior to randomization.
Two observers qualified to perform assessment of the performance status will be
required to perform this assessment. If discrepant, the one with the most
deteriorated performance status will be considered true.
* Patients must not require any help with activities of daily living (ADLs),
including eating, dressing, washing or using the toilet.
* Patients must not need to stay in bed or chair for 50% or more of waking
hours.
* Patients with factors that limit accurate assessment of performance status
will not be eligible for the study. This includes but is not limited to
patients with pre-existing conditions preventing them from full mobility
(including but not limited to spinal or orthopedic conditions, amputees, morbid
obesity defined by BMI > 40)., 4.1.7. Must have life-expectancy of > 12 weeks.,
4.1.8. Must be * 18 years of age.
* Due to increased risk of sepsis in patients >80 years old, candidate patients
in this age group should be thoroughly evaluated prior to study randomization
to ensure they are fit to receive chemotherapy. In addition to all of the
inclusion/exclusion criteria listed, clinical judgment should be used regarding
patients* susceptibility to infection (including but not limited to presence of
ascites or diabetes mellitus increasing risk of infection). Furthermore, the
expected stability of their performance status while receiving repeat weekly
chemotherapy cycles should be given special attention. Patients in this age
group should not be randomized on the study should there be any hesitation on
any of these consideratio
Patients who fulfill any of the following criteria are not eligible for
admission to the study:, 4.2.1. Patients with no evidence of metastatic disease
as well as patients with a local recurrence following surgical resection of
primary lesion., 4.2.2. Patient has experienced a decline in ECOG performance
status between Baseline visit and within 72 hours prior to randomization.,
4.2.3. Patient has a > 20% decrease in serum albumin level between Baseline
visit and within 72 hours prior to randomization., 4.2.4 Patient has a > 10%
decrease in weight between Baseline visit and within 72 hours prior to
randomization, 4.2.5. Any prior anti-cancer chemotherapy, biologic or
investigational therapy for PDAC.
a. Patients receiving immunotherapy for non-cancer related treatment within * 4
weeks of first planned dose of study treatment will be excluded.
b. A fluoropyrimidine or gemcitabine administered as a radiation sensitizer in
the adjuvant setting is allowed for as long as last dose was administered > 6
months prior to randomization., 4.2.6. Major surgery within 4 weeks prior to
randomization., 4.2.7. Any known brain or leptomeningeal metastases are
excluded, even if treated., 4.2.8. Patients with clinically significant ascites
or pleural effusions., 4.2.9. Women who are pregnant or breastfeeding. Women
should not breastfeed while taking study treatment and for 4 weeks after the
last dose of BBI-608 or while undergoing treatment with nab-paclitaxel and
gemcitabine and for 180 days after the last dose of nab-paclitaxel and
gemcitabine., 4.2.10. Gastrointestinal disorder(s) which, in the opinion of the
Principal Investigator, would significantly impede the absorption of an oral
agent (e.g. active Crohn*s disease, ulcerative colitis, extensive gastric and
small intestine resection)., 4.2.11. Unable or unwilling to swallow BBI-608
capsules daily., 4.2.12. Uncontrolled inter-current illness including, but not
limited to, ongoing or active infection, clinically significant non-healing or
healing wounds, symptomatic congestive heart failure, unstable angina pectoris,
clinically significant cardiac arrhythmia, significant pulmonary disease
(shortness of breath at rest or mild exertion), uncontrolled infection or
psychiatric illness/social situations that would limit compliance with study
requirements.
a. History of cardiac disease: congestive heart failure (CHF) > NYHA Class II;
active coronary artery disease, myocardial infarction or coronary stenting
within 6 months prior to randomization; unevaluated new onset angina within 3
months or unstable angina (angina symptoms at rest) or cardiac arrhythmias
requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted).
b. Current uncontrolled hypertension (systolic blood pressure [BP] > 150 mmHg
or diastolic pressure > 90 mmHg despite optimal medical management) as well as
prior history of hypertensive crisis or hypertensive encephalopathy.
c. Significant vascular disease (e.g., aortic aneurysm, aortic dissection,
symptomatic peripheral vascular disease including claudication, Leo Buerger*s
disease). Treated peripheral vascular disease that is stable for at least 6
months is allowed.
d. Evidence of bleeding diathesis or clinically significant coagulopathy.
e. Major surgical procedure (including open biopsy, significant t
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>To compare overall survival (OS) of patients with metastatic (Stage IV) PDAC<br /><br>treated with BBI-608 plus weekly nab-paclitaxel with gemcitabine versus weekly<br /><br>nab-paclitaxel with gemcitabine. </p><br>
- Secondary Outcome Measures
Name Time Method