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

Celgene

Status and phase: Completed; Phase 3

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

Treatments: Drug: Gemcitabine; Drug: nab-Paclitaxel

Study type: Interventional

Funder types: Industry

Identifiers

NCT01964430

2013-003398-91 (EudraCT Number)

ABI-007-PANC-003

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 866 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Histologically confirmed resected ductal pancreatic adenocarcinoma with macroscopic complete resection (R0 and R1). Subjects with neuroendocrine (and mixed type) tumors are excluded.

2. Pancreatic cancer surgical staging: Tumor (T) 1-3, Lymph Node (LN) N0-1, Metastasis (M) 0.

3. Subject should be able to start treatment no later than 12 weeks postsurgery.

4. ≥18 years of age at the time of signing the informed consent form (ICF).

5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

6. Acceptable hematology parameters:

   • Absolute neutrophil count (ANC) ≥1500 cell/mm^3
   • Platelet count ≥100,000/mm^3
   • Hemoglobin (Hgb) ≥9 g/dL

7. 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

8. Cancer antigen (CA)19-9 <100 U/mL assessed within 14 days of randomization

9. 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:

1. Prior neo-adjuvant treatment or radiation therapy for pancreatic adenocarcinoma

2. Presence of or history of metastatic pancreatic adenocarcinoma

3. 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)

4. 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

5. 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

6. History of allergy or hypersensitivity to nab-paclitaxel or gemcitabine or any of their excipients

7. 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:

   1. History of connective tissue disorders (eg, lupus, scleroderma, arteritis nodosa)
   2. History of interstitial lung disease, slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis or multiple allergies
   3. 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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866 participants in 2 patient groups

nab-Paclitaxel 125 mg/m^2 plus gemcitabine 1000 mg/m2

Experimental group

Description:

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.

Treatment:

Drug: Gemcitabine

Drug: nab-Paclitaxel

Gemcitabine 1000 mg/m^2

Active Comparator group

Description:

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.

Treatment:

Drug: Gemcitabine