Clinical trial NCT03915444: Nab-Paclitaxel + Cisplatin + Gemcitabine in Untreated Metastatic Pancreatic Adenocarcinoma
Official title: A Phase II Trial of Nab-Paclitaxel Plus Cisplatin Plus Gemcitabine in Patients With Previously Untreated Metastatic Pancreatic Ductal Adenocarcinoma
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Pancreatic Ductal Adenocarcinoma
Lead sponsor: HonorHealth Research Institute
Sponsor class: OTHER
Collaborators: name: Celgene
First posted: 2019-04-16
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Maximum age (years): 105
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a phase II open-label study evaluating the efficacy and safety of nab-paclitaxel cisplatin, and gemcitabine in patients with metastatic pancreatic ductal adenocarcinoma.

Detailed description: This is a phase II open-label study evaluating the efficacy and safety of nab-paclitaxel cisplatin, and gemcitabine in patients with metastatic pancreatic ductal adenocarcinoma.

An individual cycle of therapy will be defined as Days 1 and 8 every 21 days. Multiple cycles may be administered until the patient is withdrawn from therapy.

Overall response rates as well as individual categories of response (CR, PR, SD, and PD) will be determined using RECIST 1.1 (Frese 2012). Time-to-event endpoints, including PFS and OS will be assessed using the Kaplan-Meier method (Kaplan 1958). Evaluation of stable disease at 9 weeks will also be assessed. Toxicity (adverse events) will be recorded using the NCI CTCAE, version 5.0.

Eligibility criteria: Inclusion Criteria:

1. Age ≥ 18 years of age; male or female
2. Histologically or cytologically confirmed metastatic pancreatic ductal adenocarcinoma.
3. Capable of providing informed consent and complying with trial procedures.
4. Karnofsky Performance Status (KPS) of ≥ 70%.
5. Life expectancy ≥ 12 weeks.
6. Measurable tumor lesions according to RECIST 1.1 criteria.
7. \< Grade 2 pre-existing peripheral neuropathy per NCI CTCAE, Version 5.0
8. Patient has acceptable coagulation status as indicated by an INR ≤1.5 x ULN. Patients on anticoagulation can be included at the discretion of the investigator.
9. Patients must have normal organ and marrow function as defined below:

   * Absolute neutrophil count ≥1,500/mm3
   * Platelet concentration ≥100,000/mm3 with no platelet transfusions within 7 days prior to laboratory sample
   * Hemoglobin \> 9.0g/dL
   * Hematocrit level \> 27%
   * Total bilirubin within 1.25 times institutional upper limit of normal (ULN)
   * Alanine aminotransferase (ALT) and AST \< 10 × institutional ULN
   * Serum creatinine \<1.5 mg/dl
10. Females 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, 28 days prior to starting IP therapy (including dose interruptions), and while on study medication or for a longer period if required by local regulations following the last dose of IP; and
    2. Have a negative serum pregnancy test (β -hCG) result at screening and agree to ongoing pregnancy testing during the course of the study, and after the end of study therapy. This applies even if the subject practices true abstinence\* from heterosexual contact.
11. Male subjects must practice true abstinence\* or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for 6 months following discontinuation from study treatment, even if he has undergone a successful vasectomy.

Exclusion Criteria:

1. Patients must have received no previous radiotherapy, surgery, chemotherapy or investigational therapy for the treatment of metastatic disease. Prior treatments in the neoadjuvant and/or adjuvant setting with gemcitabine and/or 5-FU based therapies or gemcitabine and/or 5FU administered as a radiation sensitizer are allowed, provided at least 6 months have elapsed since completion of the last dose and no lingering toxicities are present.
2. Palliative surgery and/or radiation treatment less than 4 weeks prior to initiation of study treatment.
3. Exposure to any investigational agent within 4 weeks prior to initiation of study treatment.
4. Evidence of central nervous system (CNS) metastasis (negative imaging study, if clinically indicated, within 4 weeks of Screening Visit).
5. History of other malignancies (except cured basal cell carcinoma, superficial bladder cancer or carcinoma in situ of the cervix) unless documented free of cancer for ≥5 years.
6. Current, serious, clinically significant cardiac arrhythmias as determined by the investigator.
7. History of HIV infection.
8. Active, clinically significant serious infection requiring treatment with antibiotics, anti-virals or anti-fungals.
9. Major surgery within 4 weeks prior to initiation of study treatment.
10. Any condition in the opinion of the principal investigator that might interfere with the patient's participation in the study or in the evaluation of the study results.
11. Any condition in the opinion of the principal investigator that is unstable and could jeopardize the patient's participation in the study.

Primary outcomes:
measure: 12- Month Overall Survival
timeFrame: 360 days
Secondary outcomes:
measure: Change in tumor markers
timeFrame: 63 days
measure: Quality of Life: MD Anderson Symptom Inventory (MDASI-GI)
timeFrame: 63 days
measure: Pain Control: Brief Pain Inventory (BPI)
timeFrame: 63 days
measure: Potential tumor biomarkers
timeFrame: 63 days
measure: Disease Response
timeFrame: 63 days
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: HonorHealth Research Institute
state: Arizona
city: Miami
country: United States
facility: University of Miami
state: Florida
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: Milwaukee
country: United States
facility: Froedtert & Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: HonorHealth Research Institute
name: Gayle Jameson, ACNP-BC
role: PRINCIPAL_INVESTIGATOR
References: