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Nab-Paclitaxel Plus Gemcitabine Versus Gemcitabine For The First Line Treatment of Pancreas Cancer

Phase 2
Completed
Conditions
Pancreatic Neoplasm
Interventions
Registration Number
NCT03807999
Lead Sponsor
Hacettepe University
Brief Summary

This is a randomized, multicenter, phase II study of with nab-paclitaxel plus gemcitabine or gemcitabine alone for the treatment of chemotherapy-naïve patients with locally advanced or metastatic pancreatic cancer.

Arm 1: Nab-paclitaxel plus gemcitabine Arm 2: Gemcitabine alone

Detailed Description

This is a randomized, multicenter, phase II study of with nab-paclitaxel plus gemcitabine or gemcitabine alone for the treatment of chemotherapy-naïve patients with locally advanced or metastatic pancreatic cancer.

Arm 1: Nab-paclitaxel plus gemcitabine Arm 2: Gemcitabine alone

Arm 1:

Nab-paclitaxel 125 mg/m2 as 30- to 40-minute infusion (maximum infusion time not to exceed 40 minutes) once weekly for 3 weeks followed by a week of rest. plus Gemcitabine 1000 mg/m2 as a 30- to 40-minute infusion (maximum 40 minutes) once weekly for 3 weeks followed by a week of rest.

OR

Arm 2:

Gemcitabine 1000 mg/m2 as a 30- to 40-minute infusion (maximum 40 minutes) administered weekly for 7 weeks followed by a week of rest (8-week cycle; cycle 1 only), followed by cycles of weekly administration for 3 weeks (on days 1, 8, and 15) followed by one week of rest (4-week cycle).

All patients will be considered for available second-line therapies or best supportive care on the discretion of the investigators.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
125
Inclusion Criteria
  1. Written informed consent.

  2. Histologically or cytologically confirmed treatment-naïve metastatic or locally advanced adenocarcinoma of the pancreas not amenable to curative radiotherapy or surgery.

  3. Measurable disease as defined by RECIST (ie, target lesions that can be accurately measured in at least one dimension with the longest diameter ≥ 20 mm using conventional techniques or ≥ 10 mm using spiral computed tomography [CT] scan).

  4. Age ≥ 18 years.

  5. ECOG Performance Status 0 or 1.

  6. Adequate bone marrow function: granulocyte count ≥1500 and platelet count ≥100,000 per cubic millimeter.

  7. Adequate liver function as defined by the following criteria:

    • Total serum bilirubin <2 mg/dl.
    • ALP/GGT <5 x ULN.
    • Transaminases ALT/AST ≤ 2.5 x ULN.
Exclusion Criteria
  1. Any prior systemic or investigational therapy for metastatic pancreatic cancer. Systemic therapy administered alone or in combination with radiation in the adjuvant setting is permitted if it is completed > 6 months prior to the time of study enrollment.

  2. Inability to comply with study and/or follow-up procedures.

  3. Presence of significant comorbidity including clinically significant cardiac disease (e.g. congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmias not well controlled with medication) or myocardial infarction within the last 12 months and any other major organ failure.

  4. Presence of any condition that, in the opinion of the investigator, renders the subject at high risk from treatment complications or might affect the interpretation of the results of the study.

  5. Presence of central nervous system or brain metastases.

  6. Life expectancy <12 weeks.

  7. Pregnancy (positive pregnancy test) or lactation.

  8. Prior malignancy except for adequately treated basal cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other form of cancer from which the patient has been disease-free for 5 years.

  9. Lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome.

  10. Known, existing uncontrolled coagulopathy.

  11. Pre-existing sensory neuropathy > grade 1.

  12. Major surgery within 4 weeks of the start of study treatment, without complete recovery.

  13. Concurrent/pre-existing use of coumadin. 14. Patients older than 76 years of age.

  14. Patients with active infection. 16. Patients with chronic diarrhea.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Nab-paclitaxel + GemcitabineNab-paclitaxelNab-paclitaxel 125 mg/m2 as 30- to 40-minute infusion (maximum infusion time not to exceed 40 minutes) once weekly for 3 weeks followed by a week of rest. plus Gemcitabine 1000 mg/m2 as a 30- to 40-minute infusion (maximum 40 minutes) once weekly for 3 weeks followed by a week of rest.
Nab-paclitaxel + GemcitabineGemcitabineNab-paclitaxel 125 mg/m2 as 30- to 40-minute infusion (maximum infusion time not to exceed 40 minutes) once weekly for 3 weeks followed by a week of rest. plus Gemcitabine 1000 mg/m2 as a 30- to 40-minute infusion (maximum 40 minutes) once weekly for 3 weeks followed by a week of rest.
GemcitabineGemcitabineGemcitabine 1000 mg/m2 as a 30- to 40-minute infusion (maximum 40 minutes) administered weekly for 7 weeks followed by a week of rest (8-week cycle; cycle 1 only), followed by cycles of weekly administration for 3 weeks (on days 1, 8, and 15) followed by one week of rest (4-week cycle).
Primary Outcome Measures
NameTimeMethod
3-months deterioration-free rateFrom first dose of therapy to third month of therapy, 3 months

EORTC QLQ-C30 (validated version for Turkish using a reduction of at least 10 points as a meaningful clinical difference) will be used to calculate "time until definitive deterioration" (TUDD) and compare patients receiving first-line Nab-Paclitaxel plus Gemcitabine versus first-line gemcitabine for metastatic or locally advanced unresectable adenocarcinoma of the pancreas. EORTC QLQ-C30 scores will be calculated every four weeks following the EORTC QLQ-C30 recommendations for calculations and scoring (EORTC QLQ- C30 published manual).

Secondary Outcome Measures
NameTimeMethod
Overall SurvivalFrom first dose to death or end of the therapy, 24 months
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