Neoplasms

All Conditions

Digestive System Diseases

Gland and Hormone Related Diseases

Rare Diseases

Adenocarcinoma

Pancreatic Neoplasms

Pancreatic Cancer

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Durvalumab

Immunoglobulins

Antineoplastic Agents, Immunological

Patients in Arm A will be given anti-PD-L1 antibody, durvalumab, every 2 weeks for a maximum of 26 doses if there is no radiographic evidence of disease recurrence. For Arm A, one cycle constitutes two durvalumab treatments on Day 1 and Day 15, respectively, repeated every 28 days.

1500mg of Durvalumab will be given every 4 weeks (Q4W) for 12 months in patients enrolled in Arm A.

Wells Messersmith, MD

This is a two-arm, open-label, phase II study of in adult patients who have successfully undergone R0/R1 resection of PDAs following neoadjuvant chemotherapy and completion of adjuvant chemotherapy. Within 1-3 months of treatment completion, patients will be enrolled and randomized at a 1:1 ratio to receive durvalumab versus observation.

Borderline resectable pancreatic cancer (BRPC) patients who have successfully underwent R0/R1 resection of PDAs following neoadjuvant chemotherapy, between 1-3 months after the completion of planned adjuvant chemotherapy will be enrolled and randomized at a 1:1 ratio into two arms (56 per arm). Patients in Arm A will be given anti-PD-L1 antibody, durvalumab, every 2 weeks for a maximum of 26 doses if there is no radiographic evidence of disease recurrence. Patients in Arm B will be observed. Blood draws for immune monitoring and serum banking will be collected at the following time points:

Arm A - before Cycles 1, 2, 4, 7 and End of Treatment (EOT) visit; Arm B - before Cycles 1, 4, 7, and End of Treatment (EOT) visit

A Study of Durvalumab in Patients With BR PDA Following Neoadjuvant Therapy and Successful Surgical Resection

A Study of Durvalumab (MEDI4736), as an Adjuvant Therapy, Compared to Observation Alone, in Patients With Borderline Resectable Pancreatic Ductal Adenocarcinoma (BR PDA) Following Neoadjuvant Therapy and Successful Surgical Resection

Disease free survival (DFS) is defined as the time from randomization to the first of either disease recurrence or death from any cause.

OS is defined as the time from study enrollment to death from any cause.

Adverse events are measured by Common Terminology Criteria for Adverse Events (CTCAE v4.03).

AstraZeneca

University of Colorado, Denver

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Gemcitabine

Paclitaxel

Albumin-Bound Paclitaxel

Cisplatin

Tubulin Modulators

Antimitotic Agents

Antimetabolites

Patients receive nab-paclitaxel IV over 30 minutes, cisplatin IV over 60 minutes, and gemcitabine IV over 30 minutes on days 1 and 15 of each cycle. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients with stable disease, partial or complete response undergo surgical resection per standard of care. Additionally, patients undergo biopsy on study and undergo blood sample collection and CT or MRI at pre-study and on study.

Biopsy

Biospecimen Collection

Computed Tomography

Magnetic Resonance Imaging

Nab-paclitaxel

Pancreatic Surgical Procedure

Mihir M. Shah, MD

Kathleen M. Coleman

Mihir M Shah, MD

This phase II trial tests how well gemcitabine, cisplatin and nab-paclitaxel given before surgery (neoadjuvant) works in treating patients with pancreatic cancer that can be removed by surgery (resectable) or that is borderline resectable. The standard treatment for resectable and borderline resectable pancreatic cancer is a combination of surgery and chemotherapy. Neoadjuvant therapy has been shown to improve overall survival compared to patients receiving surgery first. Gemcitabine is a chemotherapy drug that blocks the cells from making DNA and may kill tumor cells. Cisplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of tumor cells. Nab-paclitaxel is an albumin-stabilized nanoparticle formulation of paclitaxel, an antimicrotubule agent that stops tumor cells from growing and dividing and may kill them. Nab-paclitaxel may have fewer side effects and work better than other forms of paclitaxel. Gemcitabine, cisplatin and nab-paclitaxel may be an effective neoadjuvant treatment option for patients with resectable or borderline resectable pancreatic cancer.

PRIMARY OBJECTIVE:

I. Determine the major pathological response rate, feasibility and safety of biweekly gemcitabine, cisplatin and nab-paclitaxel (GCN) in the neoadjuvant setting for patients with resectable and borderline resectable pancreatic ductal adenocarcinoma.

SECONDARY OBJECTIVE:

I. Determine if neoadjuvant GCN increases tumoral infiltration of lymphocytes with local and systemic phenotypic features that assist in the antitumor immune response.

OUTLINE:

Patients receive nab-paclitaxel intravenously (IV) over 30 minutes, cisplatin IV over 60 minutes, and gemcitabine IV over 30 minutes on days 1 and 15 of each cycle. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients with stable disease, partial or complete response undergo surgical resection per standard of care. Additionally, patients undergo biopsy on study and undergo blood sample collection and computed tomography (CT) or magnetic resonance imaging (MRI) at pre-study and on study.

After completion of study treatment, patients are followed up every 3-4 months for up to 24 months.

Gemcitabine, Cisplatin and Nab-Paclitaxel as Neoadjuvant Treatment for Patients With Resectable or Borderline Resectable Pancreatic Cancer

A Single-Arm Phase II Clinical Trial of Gemcitabine, Cisplatin, and Nab-Paclitaxel as Neoadjuvant Therapy for Pancreatic Ductal Adenocarcinoma

Pathologic response rate will be defined by College of American Pathologists scoring system as 0 (complete response), 1 (near complete response), 2 (partial response) and 3 (poor or no response). Pathologic response rate will be reported as a proportion of 0 and 1, with and exact 90% confidence interval estimated using the Clopper-Pearson method.

Feasibility will be defined as completion of all preoperative and operative therapy. Treatment completion will reported as a proportion, with an exact 95% confidence interval estimated using the Clopper-Pearson method.

AEs, with severity will be graded using National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Descriptive statistics will be reported, using frequencies and percentages for each toxicity.

Radiological response rate will be defined as complete response, partial response or stable disease after study treatment evaluated using Response Evaluation Criteria in Solid Tumors version 1.1. Radiologic response rate will be reported as a proportion, with an exact 95% confidence interval estimated using the Clopper-Pearson method.

R0 resection indicates a microscopically margin-negative resection. R0 resection rate will reported as a proportion, with an exact 95% confidence interval estimated using the Clopper-Pearson method.

N0, N1, and N2 will be reported using frequencies and percentages.

RFS will be estimated using the Kaplan-Meier method, and a 95% confidence interval for median RFS will be estimated using the Brookmeyer-Crowley approach.

OS will be estimated using the Kaplan-Meier method, and median survival will be calculated. A 95% confidence interval will be estimated using the Brookmeyer-Crowley approach.

CA19-9 response will be defined as \> 50% decrease from baseline will be correlated with tumor response. CA19-9 will be reported as a proportion, with an exact 95% confidence interval estimated using the Clopper-Pearson method. CA19-9 will be correlated with RFS and OS using log-rank tests and Cox proportional hazards regression. Model assumptions will be checked and verified.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of Durvalumab in Patients With BR PDA Following Neoadjuvant Therapy and Successful Surgical Resection	NCT03038477	Pancreatic Canc...	Durvalumab	18 Years - 101 Years	University of Colorado, Denver
Gemcitabine, Cisplatin and Nab-Paclitaxel as Neoadjuvant Treatment for Patients With Resectable or Borderline Resectable Pancreatic Cancer	NCT06423326	Borderline Rese... Resectable Panc... Stage I Pancrea... Stage II Pancre... Stage III Pancr...	Biopsy Biospecimen Col... Cisplatin Computed Tomogr... Gemcitabine Magnetic Resona... Nab-paclitaxel Pancreatic Surg...	18 Years -	Emory University
Gemcitabine, Cisplatin and Nab-Paclitaxel as Neoadjuvant Treatment for Patients With Resectable or Borderline Resectable Pancreatic Cancer	NCT06423326	Borderline Rese... Resectable Panc... Stage I Pancrea... Stage II Pancre... Stage III Pancr...	Biopsy Biospecimen Col... Cisplatin Computed Tomogr... Gemcitabine Magnetic Resona... Nab-paclitaxel Pancreatic Surg...	18 Years -	Emory University

Spots Global Cancer Trial Database for borderline resectable pancreatic ductal adenocarcinoma