Nab-paclitaxel and Gemcitabine vs Gemcitabine Alone as Adjuvant Therapy for Patients With Resected Pancreatic Cancer (the Apact Study)

Study Overview
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Brief Summary
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The purpose of this study is to compare whether there is a delay or prevention of recurrence or death in participants with surgically removed pancreatic cancer who then take nab-Paclitaxel in combination with gemcitabine compared to those who take gemcitabine alone.

Detailed Description
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ABI-007-PANC-003 is a Phase 3, international, multicenter, randomized, open-label, controlled study that will compare the efficacy of nab-paclitaxel in combination with gemcitabine to gemcitabine alone as adjuvant treatment for 6 cycles in patients with surgically resected pancreatic adenocarcinoma.

Official Title
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A Phase 3, Multicenter, Open-label, Randomized Study of Nab-Paclitaxel Plus Gemcitabine Versus Gemcitabine Alone as Adjuvant Therapy in Subjects With Surgically Resected Pancreatic Adenocarcinoma

Conditions
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Pancreatic Neoplasms, Digestive System Neoplasms, Neoplasms by Site, Neoplasms, Endocrine Gland Neoplasms, Pancreatic Diseases, Digestive System Diseases, Endocrine System Diseases, Gemcitabine, Antimetabolites, Antineoplastic

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: Histologically confirmed resected ductal pancreatic adenocarcinoma with macroscopic complete resection (R0 and R1). Subjects with neuroendocrine (and mixed type) tumors are excluded. Pancreatic cancer surgical staging: Tumor (T) 1-3, Lymph Node (LN) N0-1, Metastasis (M) 0. Subject should be able to start treatment no later than 12 weeks postsurgery. ≥18 years of age at the time of signing the informed consent form (ICF). Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Acceptable hematology parameters: Absolute neutrophil count (ANC) ≥1500 cell/mm^3 Platelet count ≥100,000/mm^3 Hemoglobin (Hgb) ≥9 g/dL Acceptable blood chemistry levels: Aspartate aminotransferase (AST)/ serum glutamic oxaloacetic transaminase (SGOT) and alanine transaminase (ALT)/ serum glutamic -pyruvic transaminase (SGPT) ≤2.5 × upper limit of normal range (ULN) Total bilirubin ≤ upper limit of normal (participants with Gilbert's syndrome can have bilirubin of up to 1.5 x ULN) Alkaline phosphatase ≤ 2.5 x ULN Serum creatinine within upper limits of normal or calculated clearance ≥50 mL/min/1.73 m^2. If using creatinine clearance, actual body weight should be used for calculating creatinine clearance (eg, using the Cockroft-Gault formula). For subjects with a body mass index (BMI) >30 kg/m2, lean body weight should be used instead Cancer antigen (CA)19-9 <100 U/mL assessed within 14 days of randomization Acceptable coagulation studies as demonstrated by prothrombin time (PT) and partial thromboplastin time (PTT) within normal limits (±15%) Exclusion Criteria: A subject will not be eligible for inclusion in this study if any of the following criteria apply: Prior neo-adjuvant treatment or radiation therapy for pancreatic adenocarcinoma Presence of or history of metastatic pancreatic adenocarcinoma Any other malignancy within 5 years prior to randomization, with the exception of adequately treated in-situ carcinoma of the cervix, uteri, or nonmelanomatous skin cancer (all treatment of which should have been completed 6 months prior to randomization) Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy, defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment Known infection with hepatitis B or C, or history of human immunodeficiency virus (HIV) infection, or subject receiving immunosuppressive or myelosuppressive medications that would in the opinion of the investigator, increase the risk of serious neutropenic complications History of allergy or hypersensitivity to nab-paclitaxel or gemcitabine or any of their excipients 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. These include, but are not limited to: History of connective tissue disorders (eg, lupus, scleroderma, arteritis nodosa) History of interstitial lung disease, slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis or multiple allergies History of the following within 6 months prior to Cycle 1 Day 1: 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, or seizure disorder

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: nab-Paclitaxel 125 mg/m^2 plus gemcitabine 1000 mg/m2<br>Participants received nab-Paclitaxel 125 mg/m^2 administered as an intravenous (IV) infusion over 30 to 40 minutes, followed by gemcitabine 1000 mg/m^2 as an IV infusion over 30 to 40 minutes on Days 1, 8 and 15 of each 28-day treatment cycle for 6 cycles, unless there was evidence of radiologic disease recurrence, unacceptable toxicity, subject or physician decision, withdrawal of consent, or death. | Drug: nab-Paclitaxel<br>* nab-Paclitaxel 125 mg/m^2 on Days 1, 8, and 15 of every 28 day treatment cycle by intravenous (IV) administration for a total of 6 cycles.<br>* Other names: Abraxane;Drug: Gemcitabine<br>* Gemcitabine 1000 mg/m^2 on Days 1, 8, and 15 of a 28 day cycle by IV administration for a total of 6 cycles.<br>* Other names: Gemzar;|
| Active Comparator: Gemcitabine 1000 mg/m^2<br>Participants received gemcitabine 1000 mg/m^2 administered as an IV infusion over 30 to 40 minutes on Days 1, 8 and 15 of each 28-day treatment cycle for 6 cycles, unless there was evidence of radiologic disease recurrence, unacceptable toxicity, subject or physician decision, withdrawal of consent, or death. | Drug: Gemcitabine<br>* Gemcitabine 1000 mg/m^2 on Days 1, 8, and 15 of a 28 day cycle by IV administration for a total of 6 cycles.<br>* Other names: Gemzar;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Kaplan Meier Estimate for Disease Free Survival (DFS) According to the Independent Radiological Review Committee | Disease free survival was defined as the time from the date of randomization to the date of disease recurrence or death, whichever occurred earlier. Disease recurrence was determined by the independent radiological review of computed tomography (CT) or magnetic resonance imaging (MRI) scans. Participants who did not have disease recurrence or did not die were censored at the last tumor assessment date with disease-free status or the randomization date if the last tumor assessment with disease-free status was missing. Disease-free status referred to a status that was neither being disease recurrent nor indeterminate or not evaluable. Participants who received new anti-cancer therapy or cancer-related surgery prior to disease recurrence or death were censored at the date of last tumor assessment with disease-free status prior to the start of new anti-cancer therapy or cancer-related surgery or the randomization date. | Date of randomization up to data cut off date of 31 December 2018; median DFS follow-up time for censored participants was 22.242 months for nab-Paclitaxel and gemcitabine and 13.832 months for gemcitabine alone | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Kaplan Meier Estimate of Overall Survival (OS) | Overall survival was defined as the time from the date of randomization to the date of death. Participants who were alive at the end of study or clinical data cut were censored on the last-known-to-be-alive date or the clinical cutoff date, whichever was earlier. | From randomization to date of death; median OS follow-up time for censored participants was 77.832 months for nab-Paclitaxel and gemcitabine and 77.799 months for gemcitabine alone | 
| Number of Participants With Treatment Emergent Adverse Events (TEAE's) | TEAEs are defined as any adverse event (AE) that begin or worsen on or after the start of study drug or procedure of the study period through the maximum duration of the period plus 28 days. The severity of AEs was graded based on National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0 and the scale: Grade 1 = Mild Grade 2 = Moderate Grade 3 = Severe Grade 4 = Life threatening Grade 5 = Death. Relation to study drug was determined by the investigator. A treatment-related TEAE is defined as TEAE which was considered to be related to one or both of the study drugs and reported as 'Suspected' on the case report form. AEs with a missing relationship were treated as 'treatment-related' in data summaries. IP (investigational product) refers to nab-Paclitaxel and/or Gemcitabine. Related TEAE refers to relation to study drug (IP). | From day 1 of study drug up to 28 days after the last dose of study drug; up to the data cut off date of 31 December 2018 (up to approximately 37 weeks). | 
| The Number of Participants With Clinical Chemistry Laboratory-Detected Abnormalities (Grade 3-4) | The number of participants with grade 3-4 laboratory abnormalities in selected clinically significant parameters. Grades for chemistry parameters were coded using National Cancer Institute Common Terminology Criteria for Adverse Events (Grade 3= severe, Grade 4= life-threatening). | From day 1 of study drug up to 28 days after the last dose of study drug, or the treatment discontinuation date, whichever was later (up to approximately 37 weeks). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Resectable pancreatic cancer, resected, resectable PDA, adenocarcinoma, surgically resected, adjuvant, Abraxane, nab-paclitaxel, ABI-007, gemcitabine, Gemzar, Phase 3