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

NCT02426281 | Completed Phase 2

• 1 other identifier: 2014-10-061
• Study Type: interventional
• Target: 111
• Locations: 1 country
• Sites: 8

Brief 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.

Conditions

Pancreatic Ductal Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• progression-free survival (PFS)

  The primary endpoint of the study is progression-free survival (PFS) defined as time to progression or death, whichever comes first.

  4 months

Secondary Outcomes (4)

• overall survival (OS)

  4 months

• Response rate

  4 months

• Disease control rate

  4 months

• toxicities (National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0)

  4 months

Other Outcomes (2)

• Tumor Markers (CA19-9 test)

  4 months

• Quality of life questionnaire

  4 months

Study Arms (1)

nab-paclitaxel in combination with gemcitabine

EXPERIMENTAL

nab-paclitaxel in combination with gemcitabine nab- paclitaxel 125mg/m2 in combination with gemcitabine 1000mg/m2 D1, 8 15 every 4 weeks.

Drug: nab-paclitaxel; Drug: gemcitabine

Interventions

nab-paclitaxel DRUG

nab- paclitaxel 125mg/m2 D1, 8 15 every 4 weeks.

Also known as: ABRAXANE, ABI-007

nab-paclitaxel in combination with gemcitabine

gemcitabine DRUG

gemcitabine 1000mg/m2 D1, 8 15 every 4 weeks.

nab-paclitaxel in combination with gemcitabine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed metastatic pancreatic ductal adenocarcinoma (Islet cell neoplasms or neuroendocrine carcinomas are excluded)
• ≥ 18 years of age at the time of signing the informed consent document
• ECOG 0-1
• At least one measurable lesion according to recist v1.1
• 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).
• Adequate BM function: ANC ≥1.5 × 109/L; Platelet count ≥100,000/mm2 (100 × 109/L); Hb (Hb) ≥9 g/dL.
• 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
• Albumin level ≥ 3 g/dl
• Subjects should be asymptomatic for jaundice prior to Cycle 1 Day 1
• Subject with signed the Informed Consent Form (ICF) prior to participation in any study-related activities.
• 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
• 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
• Subject able to adhere to the study visit schedule and other protocol requirements.

You may not qualify if:

• Subject has known symptomatic brain metastases.
• History of malignancy in the last 5 years.
• Breast-feeding or pregnant female
• Patients with plastic biliary stent (Metal biliary stents are allowed.)
• Subject has active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy.
• Subject has known historical or active infection with HIV, hepatitis B, or hepatitis C.
• Subject has undergone major surgery within 4 weeks prior to Cycle 1 Day 1 of treatment in this study.
• 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.
• Subject has a history of allergy or hypersensitivity to any of the study drugs
• Subjects with history of connective tissue disorders (eg, lupus, scleroderma, arteritis nodosa).
• Subjects with a history of interstitial lung disease
• 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).
• Patients has \> Grade 1 pre-existing peripheral neuropathy (per CTCAE)
• 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.
• Subject is enrolled in any other clinical protocol or investigational trial with an interventional agent or assessments that may interfere with study procedures.

Sponsors & Collaborators

• Samsung Medical Center: lead

Study Sites (8)

Dong-A University Hospital

Busan, South Korea

Location

Gyeongsang National University Hospital

Gyeongsang, South Korea

Location

CHA Bundang Medical Center

Seongnam-si, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Asan Medical Center

Seoul, South Korea

Location

Catholic University of Korea, Seoul ST. Mary's Hospital

Seoul, South Korea

Location

Seoul National University Hospital

Seoul, South Korea

Location

Severance Hospital, Yonsei Cancer Center

Seoul, South Korea

Location

MeSH Terms

Interventions

130-nm albumin-bound paclitaxel; Albumin-Bound Paclitaxel; Gemcitabine

Intervention Hierarchy (Ancestors)

Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Joonoh Park, Professor

  Samsung Medical Center

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Samsung Medical Center

Study Record Dates

• First Submitted: April 15, 2015
• First Posted: April 24, 2015
• Study Start: June 4, 2015
• Primary Completion: September 30, 2022
• Study Completion: September 30, 2022
• Last Updated: February 15, 2023

Record last verified: 2023-02

Locations

KR (8)