Perioperative Therapy for Resectable and Borderline-Resectable Pancreatic Adenocarcinoma With Molecular Correlates

Phase 2

Active, not recruiting

• Conditions: Pancreas Ductal Adenocarcinoma; Pancreatic Cancer; Pancreatic Adenocarcinoma
• Interventions: Drug: Nab paclitaxel; Drug: Gemcitabine

• Registration Number: NCT02723331
• Lead Sponsor: Academic Thoracic Oncology Medical Investigators Consortium

Brief Summary

The objective of this study is to estimate the R0 resection rate in patients with Resectable Pancreatic Ductal Adenocarcinoma (R-PDAC) as well as those with Resectable Pancreatic Ductal Adenocarcinoma (BR-PDAC) independently in response to neoadjuvant sequential therapy of combination nab-paclitaxel and gemcitabine followed by stereotactic body radiotherapy (SBRT).

Detailed Description

Patients in both cohorts will receive a total of 3 cycles of neoadjuvant combination chemotherapy of nab-paclitaxel and gemcitabine, followed by re-staging CT scan, if re-staging CT does not show evidence of metastatic disease. Patients will receive SBRT and definitive surgical resection. Subsequently, patients will receive 3 cycles of adjuvant combination chemotherapy of nab-paclitaxel and gemcitabine. Each cycle of combination chemotherapy will be a total of 4 weeks. Patients will be evaluated for response at completion of the 3 cycles of neoadjuvant combination chemotherapy with CT scans of chest, abdomen and pelvis. Patients will undergo surveillance CT scan at 3-month intervals until evidence of disease progression.

Study Timeline

• Study First Submitted: 2016-03-24
• Study First Submitted QC: 2016-03-29
• Study First Posted: 2016-03-30
• Study Start: 2016-12-30
• Primary Completion: 2022-12-08
• Disposition First Submitted: 2023-05-09
• Disposition First Posted: 2023-05-26
• Results First Submitted: 2023-12-15
• Results First Submitted QC: 2024-02-09
• Results First Posted: 2024-02-14
• Status Verified: 2024-06
• Last Update Submitted: 2024-06-18
• Last Update Posted: 2024-06-28
• Study Completion: 2025-05

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 48

Inclusion Criteria

1. Histologically confirmed resectable or borderline resectable pancreatic adenocarcinoma.

2. No evidence of distant metastasis representing stage IV metastatic disease.

3. R-PDAC: No evidence of distant metastasis and tumor mass showing no extension to superior mesenteric artery (SMA) and hepatic artery. There must be a clearly defined fat plane between SMA and celiac axis. Patent superior mesenteric vein (SMV/portal vein (PV) with no distortion of venous architecture.

4. BR-PDAC: defined as localized PDAC with 1 or more of the following features: a) an interface between the primary tumor and superior mesenteric vein (SMV)-portal vein (PV) measuring 180o or greater of the circumference of the vein wall, and/or b) short-segment occlusion of the SMV-PV with normal vein above and below the level of obstruction that is amenable to resection and venous reconstruction and/or c) short-segment interface of any degree between tumor and hepatic artery with normal artery proximal and distal to the interface that is amenable to resection and arterial reconstruction and/or d) an interface between the tumor and SMA or celiac trunk measuring less than 180o of the circumference of the artery wall.

5. Age > 18 years old

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

7. Patients must have adequate bone marrow function:

   • Platelets >100,000 cells/mm3
   • Hemoglobin > 9.0 g/dL
   • Absolute Neutrophil Count > 1,500 cells/mm3

8. Patients must have adequate liver function:

   • aspartate aminotransferase (AST) and Alanine Aminotransferase (ALT) < 2.5 X upper limit of normal
   • Alkaline phosphatase < 2.5 X upper limit of normal, unless bone metastasis is present in the absence of liver metastasis
   • Total bilirubin < 1.5 mg/dL

9. Patients must have adequate renal function: creatinine <1.5 mg/dL is recommended; however, institutional norms are acceptable. Creatinine within institutional limits of normal or creatinine clearance (CrCl) > 50 mL/min calculated using the Cockcroft-Gault equation.

10. Women of childbearing potential and sexually active males must use an effective contraception method during treatment and for three months after completing treatment.

11. Negative serum or urine β-human chorionic gonadotropin (hCG) pregnancy test at screening for patients of childbearing potential.

12. Patients must have < Grade 2 pre-existing peripheral neuropathy (per CTCAE 4.03).

13. Ability to understand and willingness to sign a written informed consent.

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Exclusion Criteria

1. Patients with locally advanced surgically unresectable PDAC.
2. Patients with evidence of distant metastatic PDAC.
3. Prior chemotherapy or radiation therapy of any kind for treatment of pancreas adenocarcinoma.
4. Prior major surgery within 4 weeks of starting study drug administration.
5. Patient unable or not willing to perform all study related biopsies and blood draws for exploratory endpoints will not be enrolled on study as all study related procedures are mandatory.
6. Concomitant treatment with full dose warfarin (coumadin) is NOT allowed. However, treatment with low molecular weight heparin (LMWH) (such as enoxaparin or dalteparin) or rivaroxaban is allowed. Patients on full dose warfarin (coumadin) must be transitioned to either LMWH or rivaroxaban prior to administration of any study related drugs.
7. Recent or ongoing clinically significant gastrointestinal disorder (e.g., malabsorption, bleeding, inflammation, emesis, diarrhea >grade 1).
8. Patients with clinically significant cardiac disease (New York Heart Association Classification III or IV and cardiac arrhythmias not well controlled with medication), or myocardial infarction within the previous six months.
9. Serious, uncontrolled, concurrent infection(s) requiring antibiotics.
10. Pregnant or breastfeeding women: positive pregnancy test within 7 days of starting treatment.
11. Treatment for other carcinomas within the last five years, except cured non-melanoma skin and treated in-situ cervical cancer.
12. Participation in any investigational drug study within 4 weeks preceding the start of study treatment.
13. Patients with external biliary drains.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Nab-paclitaxel and Gemcitabine for BR-PDAC	Nab paclitaxel	Nab-paclitaxel and gemcitabine, for BR-PDAC patients enrolled in this trial, will be given in combination as neoadjuvant combination chemotherapy, followed by SBRT. This is will be followed up by surgical resection and an additional combination chemotherapy of nab-paclitaxel and gemcitabine as adjuvant chemotherapy.
Nab-paclitaxel and Gemcitabine for R-PDAC	Nab paclitaxel	Nab-paclitaxel and gemcitabine, for R-PDAC patients enrolled in this trial, will be given in combination as neoadjuvant combination chemotherapy, followed by SBRT. This is will be followed up by surgical resection and an additional combination chemotherapy of nab-paclitaxel and gemcitabine as adjuvant chemotherapy.
Nab-paclitaxel and Gemcitabine for R-PDAC	Gemcitabine	Nab-paclitaxel and gemcitabine, for R-PDAC patients enrolled in this trial, will be given in combination as neoadjuvant combination chemotherapy, followed by SBRT. This is will be followed up by surgical resection and an additional combination chemotherapy of nab-paclitaxel and gemcitabine as adjuvant chemotherapy.
Nab-paclitaxel and Gemcitabine for BR-PDAC	Gemcitabine	Nab-paclitaxel and gemcitabine, for BR-PDAC patients enrolled in this trial, will be given in combination as neoadjuvant combination chemotherapy, followed by SBRT. This is will be followed up by surgical resection and an additional combination chemotherapy of nab-paclitaxel and gemcitabine as adjuvant chemotherapy.

Primary Outcome Measures

Name	Time	Method
R0 Resection Rates in Each Cohort as Measured by Macroscopically Complete Tumor Removal With Negative Microscopic Surgical Margins	at the time of surgery	R0 resection rates will be measured in patients with resectable PDAC and with patients with borderline-resectable PDAC, independently in response to neoadjuvant sequential therapy of combination of nab-paclitaxel and gemcitabine and SBRT, as perioperative therapy. R0 resection is determined by macroscopically complete tumor removal with negative microscopic surgical margins in the bile duct, pancreatic parenchyma, and superior mesenteric artery (SMA).

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Treatment Related Adverse Events as Assessed by CTCAE v.4.03	24 months
Median Overall Survival	Up to 74 months	Overall survival will be assessed for all participants

Trial Locations

Locations (4)

Mayo Clinic Hospital; 🇺🇸 Scottsdale, Arizona, United States

University of Colorado Cancer Center; 🇺🇸 Aurora, Colorado, United States

New York University; 🇺🇸 New York, New York, United States

University of Arizona; 🇺🇸 Tucson, Arizona, United States