Overview

Nab-pacliatxel Plus Gemcitabine in Korean Patients With Metastatic Pancreatic Ductal Adenocarcinoma

Status:
Unknown status
Trial end date:
2021-06-01
Target enrollment:
0
Participant gender:
All
Summary
Nab-paclitaxel (interchangeable with ABRAXANE and ABI-007) is a unique protein formulation of a noncrystalline, amorphous form of paclitaxel in an insoluble particle state. Nab-paclitaxel was designed to improve the chemotherapeutic effects of paclitaxel by exploiting endogenous transport pathways to deliver higher doses of paclitaxel to the tumor and to reduce the solvent-related hypersensitivity and other toxicities associated with Taxol® (paclitaxel) injections, the solvent Cremophor EL, and ethanol vehicle. Nab-paclitaxel provides more rapid tissue distribution and increased tumor accumulation compared to cremophor-EL paclitaxel. Mechanistically, albumin receptor-mediated transport across the endothelium, binding to interstitial proteins, and macropinocytic or receptor-mediated uptake into tumor cells as well as sequestration of paclitaxel by cremophor-EL may contribute to the observed differences. Furthermore, nab-paclitaxel synergizes with gemcitabine in preclinical models. The Cremophor EL-free medium enables nab-paclitaxel to be given at a higher dose and in a shorter duration without the need for premedication to prevent solvent-related hypersensitivity reactions. As of March 2014, nab-paclitaxel is approved under the trade name of ABRAXANE in over 45 countries/regions, including the US, Canada, India, European Union/European Economic Area, South Korea, China, Australia, Bhutan, United Arab Emirates, Nepal, New Zealand, Japan, Russia, Sri Lanka, Argentina, Hong Kong, and Lebanon for the treatment of patients with metastatic breast cancer. ABRAXANE is also approved for the first-line treatment of locally advanced or metastatic non small cell lung cancer (NSCLC) in the US, Japan, Argentina, Australia, and New Zealand, for treatment of advanced gastric cancer in Japan, and for first-line treatment of metastatic adenocarcinoma of the pancreas in the US, EU/EEA, Australia, New Zealand and Argentina.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Samsung Medical Center
Treatments:
Albumin-Bound Paclitaxel
Gemcitabine
Paclitaxel
Criteria
Inclusion Criteria:

1. Histologically or cytologically confirmed metastatic pancreatic ductal adenocarcinoma
(Islet cell neoplasms or neuroendocrine carcinomas are excluded)

2. ≥ 18 years of age at the time of signing the informed consent document

3. ECOG 0-1

4. At least one measurable lesion according to recist v1.1

5. No prior palliative chemotherapy for the treatment of metastatic pancreatic cancer
(Prior treatment with 5-FU or gemcitabine administered as a radiation sensitizer in
the adjuvant setting is allowed if the treatment had been received at least 6 months
before enroll).

6. Adequate BM function: ANC ≥1.5 × 109/L; Platelet count ≥100,000/mm2 (100 × 109/L); Hb
(Hb) ≥9 g/dL.

7. Adequate liver and renal function (obtained ≤14 days prior to enroll): AST (SGOT), ALT
(SGPT) ≤2.5 × upper limit of normal range (ULN), unless liver metastases are clearly
present, then ≤5 × ULN is allowed; Total bilirubin 1.5 ≤ ULN; Serum creatinine within
normal limits or calculated clearance ≥ 60 mL/min/1.73 m2

8. Albumin level ≥ 3 g/dl

9. Subjects should be asymptomatic for jaundice prior to Cycle 1 Day 1

10. Subject with signed the Informed Consent Form (ICF) prior to participation in any
study-related activities.

11. Female of childbearing potential (FCBP) (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 [ie, has had menses at any time
during the preceding 24 consecutive months]) must:

- Either commit to true abstinence or agree to the use of 2 physician-approved
contraceptive methods (oral, injectable, or implantable hormonal contraceptive;
tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or
vasectomized partner) while on IP; and for 3 months following the last dose of
IP; and

- Has a negative serum pregnancy test (β-hCG) result at screening

12. 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 IP
discontinuation, even if he has undergone a successful vasectomy

13. Subject able to adhere to the study visit schedule and other protocol requirements.

Exclusion Criteria:

1. Subject has known symptomatic brain metastases.

2. History of malignancy in the last 5 years.

3. Breast-feeding or pregnant female

4. Patients with plastic biliary stent (Metal biliary stents are allowed.)

5. Subject has active, uncontrolled bacterial, viral, or fungal infection(s) requiring
systemic therapy.

6. Subject has known historical or active infection with HIV, hepatitis B, or hepatitis
C.

7. Subject has undergone major surgery within 4 weeks prior to Cycle 1 Day 1 of treatment
in this study.

8. Subject who experienced a recent myocardial infarction, including severe/unstable
angina pectoris, coronary/peripheral artery bypass graft, uncontrolled hypertension,
clinically significant cardiac dysrhythmia or clinically significant electrocardiogram
(ECG) abnormality, significant or uncontrolled cardiovascular disease CHF, and
cerebrovascular accident or transient ischemic attack, or seizure disorder in the past
year.

9. Subject has a history of allergy or hypersensitivity to any of the study drugs

10. Subjects with history of connective tissue disorders (eg, lupus, scleroderma,
arteritis nodosa).

11. Subjects with a history of interstitial lung disease

12. Any other malignancy within 5 years prior to enrollment, with the exception of
adequately treated in-situ carcinoma of the prostate (Gleason score ≤ 7), cervix,
uteri, or nonmelanomatous skin cancer (all treatment of which should have been
completed 6 months prior to enrollment).

13. Patients has > Grade 1 pre-existing peripheral neuropathy (per CTCAE)

14. Subject has serious medical risk factors involving any of the major organ systems, or
serious psychiatric disorders, which could compromise the subject's safety or the
study data integrity.

15. Subject is enrolled in any other clinical protocol or investigational trial with an
interventional agent or assessments that may interfere with study procedures.

16. Subject is unwilling or unable to comply with study procedures

17. Any significant medical condition, laboratory abnormality, or psychiatric illness that
would prevent the subject from participating in the study.