Safety and Efficacy Study of Nab-paclitaxel Plus Gemcitabine in Chinese Patients With Metastatic Pancreatic Cancer

Study Overview
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Brief Summary
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The purpose of this study is to determine the safety and efficacy of nab-paclitaxel combined with gemcitabine in Chinese patients with metastatic pancreatic cancer.

Detailed Description
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This is a Phase 2 trial in China to evaluate the safety and efficacy of the combination of nab-paclitaxel and gemcitabine administered in patients diagnosed with metastatic pancreatic adenocarcinoma. This study is designed to be a Chinese bridging study to complement the Global pivotal study (CA-046). The study consists of three parts: (1) Dose evaluation; (2) Single arm to evaluate efficacy following an optimal Simon two-stage design; and (3) Randomized 2-arm to evaluate the efficacy and safety of nab-paclitaxel plus gemcitabine versus gemcitabine alone. These 3 parts will be carried out sequentially. The Part 3 randomized 2-arm portion will only be carried out if deemed necessary per protocol.

Official Title
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A PHASE 2, MULTI-CENTER STUDY TO EVALUATE THE SAFETY AND EFFICACY OF ABI-007 PLUS GEMCITABINE IN CHINESE PATEINTS WITH METASTATIC PANCREATIC ADENOCARCINOMA

Conditions
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Pancreatic Neoplasms

Intervention / Treatment
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* Drug: nab-paclitaxel
* Drug: Gemcitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient has definitive histologically or cytologically confirmed metastatic pancreatic adenocarcinoma (Islet cell neoplasms are excluded) that is measurable by Response Evaluation criteria for solid tumors (RECIST V1.0) Patients must have received no previous radiotherapy, surgery, chemotherapy or investigational therapy for the treatment of metastatic pancreatic cancer. Prior treatment with 5-fluorouracil (5-FU) or gemcitabine administered as a radiation sensitizer in the adjuvant setting is allowed, provided at least 6 months have elapsed since completion of the last dose and no lingering toxicities are present. Patients having received cytotoxic doses of gemcitabine or any other chemotherapy in the adjuvant setting are not eligible for this study Patient has a Karnofsky performance status (KPS) ≥ 70 Initial diagnosis of metastatic disease must have occurred ≤ 6 weeks prior to starting Cycle 1 Day 1. NOTE: the clock for this time interval starts with the date of last evaluation confirming pancreatic metastatic disease (either biopsy or imaging results) Patients should be asymptomatic for jaundice prior to Cycle 1 Day 1. Significant or symptomatic amounts of ascites should be drained prior to Cycle 1 Day 1. Pain symptoms should be stable and should not require modifications in analgesic management prior to Cycle 1 Day 1 Patient has adequate blood counts at screening (obtained ≤ 14 days prior to starting Cycle 1 Day 1): Absolute neutrophil count (ANC) ≥ 1.5 × 10^9/L; Platelet count ≥ 100,000/mm^3 (100 × 10^9/L); Hemoglobin (Hgb) ≥ 9 g/dL Patient has the following blood chemistry levels at Screening (obtained ≤ 14 days prior to starting Cycle 1 Day 1): Aspartate aminotransferase (SGOT) and alanine transaminase (SGPT) are ≤ 2.5 upper limit of normal (ULN) range, unless liver metastases are clearly present, then ≤ 5 × upper limit of normal (ULN) range is allowed Total bilirubin ≤ upper limit of normal range Serum creatinine within normal limits or calculated clearance ≥ 60 mL/min/1.73 m^2 for patients with serum creatinine levels above or below the institutional normal value. If using creatinine clearance, actual body weight should be used for calculating creatinine clearance (eg, using the Cockcroft-Gault formula). For patients with a body mass index (BMI) > 30 kg/m^2, lean body weight should be used instead. The patient has acceptable coagulation studies (obtained ≤14 days prior to starting Cycle 1 Day 1) as demonstrated by prothrombin time (PT) and partial thromboplastin time (PTT) within normal limits (WNL) ±15%. The patient has no clinically significant abnormalities in urinalysis results (obtained ≤14 days prior to starting Cycle 1 Day 1). Male or non-pregnant and non-lactating female, and ≥ 18 years of age at the time of signing the informed consent document. If a female patient is of child-bearing potential, as evidenced by regular menstrual periods, she must have a negative pregnancy test (e.g. serum β-subunit of human chorionic gonadotropin (β-hCG) documented prior to the first administration of study drug. If sexually active, the patient must agree to use contraception considered adequate and appropriate by the Investigator during the period of administration of study drug. In addition, male and female patients must utilize contraception after the end of treatment as recommended in the product's Patient has been informed about the nature of the study, and has agreed to participate in the study, and signed the Informed Consent Form prior to participation in any study-related activities. Able to adhere to the study visit schedule and other protocol requirements. Exclusion Criteria: Patient has known brain metastases Patient has only locally advanced disease. Patient has a ≥ 20% decrease in serum albumin level between Screening visit and within 72 hours prior to Cycle 1 Day 1. History of malignancy in the last 5 years (including chronic leukemias). Patients with prior history of in situ cancer or basal or squamous cell skin cancer are eligible. Patients with other malignancies are eligible if they were cured by surgery alone or surgery plus radiotherapy and have been continuously disease-free for at least 5 years. Patient has active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy. Patient has known infection with human immunodeficiency virus, and/or active infection with hepatitis B, or hepatitis C (patients with known historical infection with hepatitis B or C should be discussed with the Sponsor). Patient has undergone major surgery, other than diagnostic surgery (ie, surgery done to obtain a biopsy for diagnosis without removal of an organ), within 4 weeks prior to Day 1 of treatment in this study. Patient that has a history of a myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, New York Heart Association (NYHA) Class III-IV heart failure, uncontrolled hypertension, clinically significant cardiac dysrhythmia or electrocardiogram (ECG) abnormality, cerebrovascular accident, transient ischemic attack, seizure disorder or clinically significant cardiac dysrhythmia or ECG abnormality, within 6 months prior to Cycle 1 Day 1 Patient has a history of allergy or hypersensitivity to any of the study drugs or any of their excipients, or the patient exhibits any of the adverse events . History of connective tissue disorders (eg, lupus, scleroderma, arteritis nodosa). Patients with a history of interstitial lung disease, history of slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis or multiple allergies. Patient has any condition, including serious medical risk factors, medical conditions, laboratory abnormalities or psychiatric disorders, which could compromise the patient's safety or the study data integrity. Patient is enrolled in any other clinical protocol or investigational trial with an interventional agent or assessments that may interfere with study procedures. Patient is unwilling or unable to comply with study procedures, or is planning to take vacation for 7 or more consecutive days during the treatment phase of the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: nab-paclitaxel with gemcitabine<br>nab-paclitaxel at 125 mg/m^2, intravenous (IV) infusion over 30 to 40 minutes followed by gemcitabine at 1000 mg/ m^2 IV infusion over 30 to 40 minutes given once weekly for 3 weeks (Days 1, 8 and 15) followed by a week of rest (28 day cycle). | Drug: nab-paclitaxel<br>* nab-paclitaxel at 125 mg/m^2, by IV infusion over 30 to 40 minutes (maximum infusion time not to exceed 40 minutes)<br>* Other names: Abraxane;Drug: Gemcitabine<br>* Gemcitabine at 1000 mg/m^2 IV infusion over 30 to 40 minutes given once weekly for 3 weeks (Days 1, 8 and 15) followed by a week of rest (28 day cycle).<br>* Other names: Gemzar;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) Based on Independent Radiological Review (IRR) | ORR was defined as the percentage of participants who achieve a complete response (CR) or partial response (PR) based on independent radiological review per Response Evaluation Criteria in Solid Tumors (RECIST) Criteria (V1.0). Using RECIST Version 1.0, participants were to achieve either a complete response defined as the disappearance of all known disease and no new sites or disease related symptoms confirmed at least 4 weeks after initial documentation or partial response defined as at least a 30% decrease in the sum of the longest diameters of target lesions and no progression in non-target lesions based on confirmed responses from the independent radiological review of best overall response during study treatment. | Assessment every 8 weeks; Day 1 to data cut off of 01 June 2015; Up to approximately 70 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Experiencing Treatment Emergent Adverse Events (TEAE) | TEAEs were defined as adverse events (AEs) that began or worsened in severity on or after the date of the first dose of study drug and within 30 days of the last dose of study drug. A Serious AE (SAE) = any AE that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability, is a congenital anomaly/birth defect; constitutes an important medical event. Treatment-related AEs (TRAEs) were any TEAEs considered to be related to the study drug. A TRAE is a TEAE with relationship as suspected to either ABI-007 or gemcitabine The intensity of AEs were graded 1 to 5 according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0. Other AEs not described in the CTCAE criteria, the intensity will be assessed by the investigator as mild grade (Gr 1), moderate (grade 2), severe (grade 3), life-threatening (grade 4) or death (grade 5) | Study drug initiation through 30 days after the last dose of study drug or End Of Study, whichever is later; maximum treatment duration was 54.9 weeks | 
| Duration of Response (DoR) Based on IRR According to RECIST Guidelines | DoR was defined as the time from the first tumor assessment when the confirmed CR/PR response criterion is met to the date of disease progression based on IRR following RECIST 1.0. Only for those participants with a confirmed CR/PR. If a participant had disease progression, then the date of disease progression was the event date. For a participant who did not develop disease progression or disease progression occurred after 2 or more missing tumor assessments, the participant was censored on the date of last tumor assessment where the participant was documented to be progression free. If a participant died prior to disease progression, the participant was censored on the date of death. If patient started new anti-cancer therapy, the patient was censored on the last tumor assessment date on or prior to the start date of new anti-cancer therapy | Assessment performed every 8 weeks; from the first participant enrolled to cut off date of 01 June 2015; up to approximately 70 weeks | 
| Kaplan-Meier Estimate of Overall Survival (OS) | Overall survival was defined as the time from the date of first treatment to the date of death. Participants who did not die at the end of study or clinical data cut were censored on the last-known-to-be-alive date or the clinical cut-off date, whichever was earlier. | From the first participant enrolled to data cut off of 01 June 2015; up to approximately 70 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pancreatic cancer, Metastatic pancreatic cancer, treatment for pancreatic cancer, Abraxane clinical research trials, Celgene clinical research trials