Clinical trial NCT03703089: Gemcitabine & Nab-Paclitaxel in Pancreatic Adenocarcinoma With Positive Peritoneal Cytology
Official title: Gemcitabine and Nab-Paclitaxel in Pancreatic Adenocarcinoma With Positive Peritoneal Cytology as a Sole Metastatic Site, a Pilot Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Pancreatic Adenocarcinoma
Keywords: Positive Peritoneal Cytology
Lead sponsor: Benaroya Research Institute
Sponsor class: OTHER
First posted: 2018-10-11
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Using gemcitabine and nab-paclitaxel, the investigators hope to establish the differential ability of local and cytologically positive disease to respond to this regimen, and in particular, the frequency of cytologic conversion from positive to negative in such patients. The investigators also can begin to assess the value of maximum local therapy, including surgery, in patients who cytologically convert from positive to negative.

Detailed description: This research study is a Phase Ib clinical trial. It will assess the frequency of cytological conversion in patients with pancreatic adenocarcinoma and positive peritoneal cytology as a sole metastatic site following gemcitabine nab-paclitaxel.

Subjects must have a newly diagnosed stage 4 untreated metastatic pancreatic ductal cancer with positive peritoneal cytology as a sole metastatic site and meet all inclusion/exclusion criteria.

Treatment consists of 4 week treatment cycles. Nab-paclitaxel and gemcitabine will be administered on days 1,8, and 15.

Eligibility criteria: Inclusion Criteria:

1. Male, or a non-pregnant and non-lactating female.
2. Age ≥ 18 years.
3. Histologically proven diagnosis of pancreatic ductal adenocarcinoma (PDAC).
4. Radiographic and pathologic staging (including staging laparoscopy with peritoneal wash) consistent with pancreatic cancer, resectable, borderline resectable, or locally advanced or unresectable as defined by NCCN guidelines (http://www.nccn.org/professionals/physician_gls/f_guidelines.asp).
5. Laparoscopic confirmation that the PDAC is localized except for positive peritoneal cytology. Biliary stents are permitted.
6. Elevated CA19-9.
7. Measurable disease as defined by RECIST 1.1.
8. ECOG performance status of ≤ 1 (see Appendix A).
9. Adequate bone marrow reserves as evidenced by:

   * ANC ≥1,500 cells/μl; and
   * Platelet count ≥100,000 cells/μl; and
   * Hemoglobin ≥9 g/dL
10. Adequate hepatic function as evidenced by:

    * Serum total bilirubin 1.5 ≤; and
    * AST and ALT ≤2.5 x ULN; and
    * Alkaline phosphatase ≤2.5 x ULN
11. Adequate renal function as evidenced by creatinine ≤1.5 x ULN.
12. Women of child-bearing potential (defined as a sexually mature woman who (1) has not undergone hysterectomy \[the surgical removal of the uterus\] or bilateral oophorectomy \[the surgical removal of both ovaries\] or (2) has not been naturally postmenopausal for at least 24 consecutive months \[i.e., has had menses at any time during the preceding 24 consecutive months\]) must:

    1. Either commit to true abstinence from heterosexual contact (which must be reviewed on a monthly basis), or agree to use, and be able to comply with, effective contraception without interruption for 28 days prior to starting gemcitabine/nab- paclitaxel (including dose interruptions) and for 3 months after last dose of gemcitabine/nab-paclitaxel and
    2. Have a negative pregnancy test result at screening and agree to ongoing pregnancy testing at the Investigator's discretion during the course of the study. This applies even if the subject practices true abstinence from heterosexual contact.
13. Male subjects must practice true abstinence or agree to use a condom during sexual contact with a female of childbearing potential or a pregnant female while on treatment (including during dose interruptions) with gemcitabine/nab-paclitaxel and for 3 months following the last dose of gemcitabine/nab- paclitaxel, even if he has undergone a successful vasectomy.

Exclusion Criteria:

1. Prior chemotherapy or radiation for pancreatic cancer.
2. CA19-9 non-expressing.
3. Previous (within the past 5 years) or concurrent, malignancy diagnosis, except non-melanoma skin cancer and in situ carcinomas.
4. History of allergy or hypersensitivity to human, humanized or chimeric monoclonal antibodies.
5. Any medical or surgical condition that may place the subject at increased risk while on study.
6. Any condition potentially decreasing compliance to study procedures.
7. Participation in any other clinical protocol or investigational trials within 60 days prior to Day 1, Cycle 1.
8. Uncontrolled intercurrent illness including, but not limited to, ongoing or active systemic infection, symptomatic congestive heart failure, unstable angina pectoris, clinically significant cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
9. Current abuse of alcohol or illicit drugs.
10. Any medical condition that, in the opinion of the Investigator, may pose a safety risk to the subject, may confound the assessment of safety and efficacy, or may interfere with study participation.
11. Have ≥ Grade 2 pre-existing peripheral neuropathy (per CTCAE).
12. Inability or unwillingness to sign the informed consent form.

Primary outcomes:
measure: Frequency of cytological conversion
timeFrame: An average of 6 months
Secondary outcomes:
measure: Progression-free survival (PFS)
timeFrame: Up to 5 years
measure: Overall survival (OS)
timeFrame: Up to 5 years
measure: Overall response rate
timeFrame: Up to 5 years
measure: Response rate by CA19-9
timeFrame: An average of 1 year
measure: Response rate by RECIST criteria 1.1
timeFrame: Assessment approximately every 8 weeks during treatment up to 5 years
measure: Ability to achieve R0 (complete)
timeFrame: At time of surgery, approximately 6 months after enrollment
measure: Local disease control rate.
timeFrame: Baseline, and approximately every 8 weeks during treatment. Up to 5 years
measure: Pattern of disease recurrence
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: Seattle
country: United States
facility: Virginia mason medical Center
state: Washington
Study officials:
affiliation: Virginia mason medical Center
name: Vincent J Picozzi, MD
role: PRINCIPAL_INVESTIGATOR
References: