Neoplasms

All Conditions

Digestive System Diseases

Gland and Hormone Related Diseases

Rare Diseases

Adenocarcinoma

Pancreatic Neoplasms

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Antineoplastic Agents

All Drugs and Chemicals

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.

National Cancer Institute (NCI)

Emory University

Principal Investigator

Capecitabine

Docetaxel

Oxaliplatin

gemcitabine hydrochloride

docetaxel

capecitabine

intensity-modulated radiation therapy

oxaliplatin

pancreatic surgical procedure

therapeutic conventional surgery

laboratory biomarker analysis

Andrew Coveler

This phase II trial studies how well giving combination chemotherapy together with intensity-modulated radiation therapy (IMRT) and surgery works in treating patients with localized pancreatic cancer that can be removed by surgery. Drugs used in chemotherapy, such as gemcitabine hydrochloride, docetaxel, capecitabine, and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Specialized radiation therapy, such as IMRT, that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Giving more than one drug (combination chemotherapy) together with intensity-modulated radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving chemotherapy after surgery may kill any tumor cells that remain after surgery.

PRIMARY OBJECTIVES:

I. To estimate the median overall survival of patients with adenocarcinoma of the pancreas treated with induction chemotherapy, neoadjuvant chemoradiotherapy, surgical resection and adjuvant chemotherapy.

SECONDARY OBJECTIVES:

I. To determine the percent of patients surviving at annual intervals through five years.

II. To determine the median recurrence free survival following pancreaticoduodenectomy.

III. To determine the clinical response rate to neoadjuvant chemotherapy and chemoradiotherapy.

IV. To determine the pathologic response rate to neoadjuvant chemotherapy and chemoradiotherapy.

V. To determine the cancer antigen (CA) 19-9 tumor marker response rate to neoadjuvant chemotherapy and chemoradiotherapy.

VI. To determine the surgical completion rate and complication rate following neoadjuvant chemotherapy and chemoradiotherapy.

VII. To determine the frequency and severity of toxicities associated with this treatment regimen.

OUTLINE:

INDUCTION CHEMOTHERAPY: Patients receive gemcitabine hydrochloride intravenously (IV) over 75 minutes and docetaxel IV over 30 or 60 minutes on days 4 and 11. Patients also receive capecitabine orally (PO) twice daily (BID) on days 1-14. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity.

NEOADJUVANT CHEMORADIOTHERAPY: Beginning no more than 14 days after completion of induction chemotherapy, patients receive capecitabine PO BID on days 1-14 and oxaliplatin IV over 2 hours on days 1 and 8. Patients also undergo IMRT once daily on days 1-5 and 8-13.

SURGICAL RESECTION: Approximately 2-6 weeks after completion of neoadjuvant chemoradiotherapy, patients undergo pancreaticoduodenectomy.

ADJUVANT CHEMOTHERAPY: Beginning 4-10 weeks after surgery, patients receive gemcitabine hydrochloride IV over 30 minutes and oxaliplatin IV over 2 hours on day 1. Treatment repeats every 14 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients then receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months.

Perioperative Therapy for Resectable Pancreatic Cancer

A Phase II Study Induction Chemotherapy, Neoadjuvant Chemoradiotherapy, Surgical Resection and Adjuvant Chemotherapy for Patients With Locally Advanced, Resectable Pancreatic Adenocarcinoma

Time at which Kaplan-Meier estimate of overall survival drops below 50%

Kaplan-Meier estimate of overall survival at 5 years

The appearance of radiographic findings consistent with recurrent tumor at the local resection site or at a distant location is considered a radiographic recurrence.

Assessed using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee.

The resected pancreaticoduodenectomy specimen and accompanying lymph nodes will be staged according to American Joint Committee on Cancer 6th Edition incorporating the prefix y to indicate a specimen status-post neoadjuvant treatment (ypTNM). Cancer 2012;118:1382-90

Biochemical response is a decrease of \>= 50% of CA 19-9 serum tumor marker in patients with elevated CA 19-9 at baseline.

University of Washington

See Detailed Description

gemcitabine hydrochloride: Given IV

docetaxel: Given IV

capecitabine: Given PO

intensity-modulated radiation therapy: Undergo IMRT

oxaliplatin: Given IV

pancreatic surgical procedure: Undergo pancreaticoduodenectomy

therapeutic conventional surgery: Undergo therapeutic conventional surgery

gemcitabine: Given IV

oxaliplatin: Given IV

Treatment (Chemotherapy, Radiation, Pancreaticoduodenectomy)

See Detailed Description

gemcitabine hydrochloride: Given IV

docetaxel: Given IV

capecitabine: Given PO

intensity-modulated radiation therapy: Undergo IMRT

oxaliplatin: Given IV

pancreatic surgical procedure: Undergo pancreaticoduodenectomy

therapeutic conventional surgery: Undergo therapeutic conventional surgery

laboratory biomarker analysis: Correlative studies

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Andrew Coveler, MD

Median Overall Survival of Patients With Adenocarcinoma of the Pancreas

Percent of Patients Surviving at 5 Years

Among eligible patients who received surgery

Median Recurrence Free Survival Following Pancreaticoduodenectomy

Clinical Response Rate to Neoadjuvant Chemotherapy and Chemoradiotherapy

all eligible patients with non-missing data

Pathologic Response Rate (Complete, Near-complete, Partial) to Neoadjuvant Chemotherapy and Chemoradiotherapy

CA 19-9 Tumor Marker Response Rate to Neoadjuvant Chemotherapy and Chemoradiotherapy

Completion rate

Complication rate

Surgical Completion Rate and Complication Rate

Any Grade 2 CTCAE toxicity

Any Grade 3 CTCAE toxicity

Any Grade 4 CTCAE toxicity

Frequency and Severity of Toxicities Associated With This Treatment Regimen as Assessed by NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
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
Perioperative Therapy for Resectable Pancreatic Cancer	NCT00609336	Adenocarcinoma ... Stage IA Pancre... Stage IB Pancre... Stage IIA Pancr... Stage IIB Pancr...	gemcitabine hyd... docetaxel capecitabine intensity-modul... oxaliplatin pancreatic surg... therapeutic con... laboratory biom...	18 Years -	University of Washington
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
Perioperative Therapy for Resectable Pancreatic Cancer	NCT00609336	Adenocarcinoma ... Stage IA Pancre... Stage IB Pancre... Stage IIA Pancr... Stage IIB Pancr...	gemcitabine hyd... docetaxel capecitabine intensity-modul... oxaliplatin pancreatic surg... therapeutic con... laboratory biom...	18 Years -	University of Washington

Spots Global Cancer Trial Database for pancreatic surgical procedure