Phase II Neoadjuvant Chemotheraphy (Gemcitabine and Nab-Paclitaxel vs. mFOLFIRINOX) and Sterotatic Body Radiation Therapy for Borderline Resectable Pancreatic Cancer

• Sponsor: Nathan Bahary, MD (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02241551
• Collaborator: (none)
• Enrollment: 2
• Location: 1
• Arms: 2
• Duration (Months): 27
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is a prospective, randomized phase II trial. Patients diagnosed with borderline resectable pancreatic adenocarcinoma will be randomly assigned to one of two treatment arms, either mFOLFIRINOX or gemcitabine and nab-paclitaxel. After three cycles of treatment in the gemcitabine/nab-paclitaxel arm and 6 cycles in the mFOLFIRINOX arm, patients will be restaged with CT scans and if they remain borderline resectable or have improvement of their disease They will then proceed to SBRT followed by surgical resection.

Condition or Disease	Intervention/Treatment	Phase
Borderline Resectable Pancreatic Cancer	Drug: gemcitabine/nab-paclitaxel; Drug: mFOLFIRINOX	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 2 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of Neoadjuvant Chemotheraphy (Gemcitabine and Nab-Paclitaxel vs. mFOLFIRINOX) and Sterotatic Body Radiation Therapy for Borderline Resectable Pancreatic Cancer
• Study Start Date: Dec 1, 2014
• Actual Primary Completion Date: Mar 3, 2017
• Actual Study Completion Date: Mar 3, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: gemcitabine/nab-paclitaxel three cycles of treatment in the gemcitabine/nab-paclitaxel	Drug: gemcitabine/nab-paclitaxel; three cycles of treatment in the gemcitabine/nab-paclitaxel; Other Names: Gemzar ABRAXANE
Experimental: mFOLFIRINOX 6 cycles in the mFOLFIRINOX	Drug: mFOLFIRINOX; 6 cycles in the mFOLFIRINOX; Other Names: irinotecan fluorouracil oxaliplatin

Outcome Measures

Primary Outcome Measures

1. Safety and Efficacy Using Neo-adjuvant Gemcitabine Plus Nab-paclitaxel in Patients Receiving SBRT and Surgery for Borderline Resectable Pancreatic Cancer, Using Neo-adjuvant mFOLFIRINOX as a Control [up to 5 years]

   Efficacy: pathological complete response (pCR) and R0 resection. Safety: Grade 4 toxicity.

Secondary Outcome Measures

1. R0 Resection Rates in Borderline Resectable Pancreatic Cancer [Up to 5 years]

2. Incidence of Grade 3 and 4 Toxicities for the 2 Chemotherapy Regimens That Occur After Cycle 1 Day 1 [Up to 5 years]

   According to the National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTAE, v4.0)

3. Ca19-9 Response to Neoadjuvant Chemotherapy [Up to 5 years]

4. Time to Disease Progression [Up to 5 years]

5. Measurement of Biomarkers (SPARC, RM1 and SMAD4) in Tissues [Up to 5 years]

   This wil be measured in tissues that are obtained at screening and in the resected tumour specimen

6. Radiological Response Rate to Therapy [Up to 5 years]

   Radiological improvements will be evaluated by determining changes in density of measurable disease on CT scan pre and post chemotherapy

7. Quality of Life Effects of Chemotherapy on Patients Receiving Chemotherapy and SBRT [Up to 5 years]

   This will be measured using the FACT-HB questionaire

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

All patients must meet the following criteria within 28 days of randomization (unless otherwise indicated) to be enrolled in the protocol:

• Histologically or cytologically proven adenocarcinoma of the pancreas. If the patient has mixed tumor with predominant adenocarcinoma pathology, they can be enrolled.

• Subjects will be staged according to the 2010 American Joint Committee on Cancer (AJCC) staging system with pathologic stage T1-4, N0 being eligible; and have a primary tumor of the pancreas (either pancreatic head, neck, uncinate process, or body/tail)

• The tumor must be deemed as being borderline resectable. Final CT confirmation of surgical staging/ eligibility will be at the discretion of the pancreatic surgeon of the patient.

• Disease is confined to locoregional site as confirmed by the CT and / or diagnostic staging laparoscopy to avoid occult peritoneal deposits. Diagnostic laproscopy will be only if absolutely required

• Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) on imaging studies CT

• Screening Endoscopic ultrasound if done prior to consent but within 6 weeks of expected randomization date it may be used.

• Karnofsky performance status greater than or equal to 70 or Eastern Cooperative Oncology Group (ECOG) performance of 0-2.

• Age > 18

• Estimated life expectance > 12 weeks

• If female patient is of child bearing potential, she must have a negative serum pregnancy test (βhCG) documented up to 72hrs prior to administration of first study drug

• Patient has screening blood work performed which includes the following (should be drawn ≤ 14 days prior to randomization)

• absolute neutrophil count (ANC) > 1.5 x 109/L

• Platelet count ≥ 100000/mm3

• Hemoglobin (HgB) ≥ 9g/dL

• aspartate aminotransferase (AST),Alanine Aminotransferase (ALT)≤ 2.5 x upper limit of normal (ULN) Total Bilirubin ≤ ULN

• Serum Cr within normal limits (WNL)

• Coagulation studies with Prothrombin Time and International Normalized Ratio (PT/INR) and partial thromboplastin time (PTT) within normal limits (±15%). • Patient has a urinalysis obtained (≤14 days prior to randomization) and the results are deemed not clinically significant by the investigator.

• Patient has no evidence of jaundice at the time of enrolment. If stent is required to alleviate jaundice, it should be metallic. If patient has a previously placed stent and this is plastic, this should be changed to metallic.

• Patient's pain symptoms have remained stable with no adjustment to analgesics within 7 days prior to randomization. Patient must be able to swallow entreat medications with no requirement for a feeding tube. Patient's must not have intractable nausea or vomiting which prohibits the patient from oral medications

• Diabetes must be controlled prior to enrollment

• Disease must be encompassed in a reasonable SBRT "portal" as defined by the treating radiation oncologist

Exclusion Criteria:

• Ineligible Histology including non-adenocarcinomas, adenosquamous carcinoma, islet cell carcinomas, cystadenomas, cystadenocarcinomas, carcinoid tumors, duodenal carcinomas, distal bile duct and ampullary carcinomas

• Evidence of distant metastasis on upright chest x-ray, CT or other staging studies

• Subjects with recurrent disease

• Prior radiation therapy to the upper abdomen or liver at the discretion of the treating radiation oncologist could impair delivery of the prescribed radiation treatment

• Prior chemotherapy

• Subjects in their reproductive age who are breast feeding or have a positive pregnancy test

• Any co-morbid condition of sufficient severity to limit full compliance with the protocol per assessment by the individual treating physician

• Concurrent active infection

• Previous or current malignancies of other histologies within the last 3 yrs prior to randomization; with the exception of cervical cancer in situ, adequately treated basal cell or squamous cell carcinoma of skin or treated low risk prostate cancer

• Patient with known historical or active infection with HIV, Hepatitis B or Hepatitis C

• Patient who has undergone recent major surgery, other than diagnostic surgical procedure within 4 weeks prior to randomization.

• Patient who has a history of allergy or hypersensitivity to any of the study drugs.

• Patients with a history of interstitial lung disease, history of slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, interstitial pulmonary fibrosis, pulmonary hypersensitivity pneumonitis or multiple allergies

• Patients with greater than 2 screening peripheral neuropathy.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hillman Cancer Center	Pittsburgh	Pennsylvania	United States	15232

Sponsors and Collaborators

• Nathan Bahary, MD

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 27, 2015

More Information

Publications

None provided.

• Responsible Party: Nathan Bahary, MD, Associate Professor, University of Pittsburgh
• ClinicalTrials.gov Identifier: NCT02241551
• Other Study ID Numbers: UPCI 13-143
• First Posted: Sep 16, 2014
• Last Update Posted: Jul 26, 2018
• Last Verified: Jun 1, 2018

• Keywords provided by Nathan Bahary, MD, Associate Professor, University of Pittsburgh: Borderline; Resectable; Pancreatic; Cancer; Neoadjuvant; Chemotheraphy; Gemcitabine; Nab-Paclitaxel; mFOFIRINOX; Sterotatic Body Radiation Therapy
• Additional relevant MeSH terms: Pancreatic Neoplasms; Gemcitabine; Paclitaxel; Fluorouracil; Oxaliplatin; Irinotecan

Study Results

Participant Flow

Arm/Group Title	Gemcitabine/Nab-paclitaxel	mFOLFIRINOX
Arm/Group Description	Patients that received three cycles of treatment in the gemcitabine/nab-paclitaxel	Patients that received 6 cycles in the mFOLFIRINOX
Period Title: Overall Study
STARTED	1	0
COMPLETED	0	0
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	Gemcitabine/Nab-paclitaxel	mFOLFIRINOX	Total
Arm/Group Description	Patients that received three cycles of treatment in the gemcitabine/nab-paclitaxel	Patients that received 6 cycles in the mFOLFIRINOX	Total of all reporting groups
Overall Participants	1	0	1
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	54	54
Sex: Female, Male (Count of Participants)
Female	1 100%	0 NaN	1 100%
Male	0 0%	0 NaN	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 NaN	0 0%
Asian	0 0%	0 NaN	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 NaN	0 0%
Black or African American	1 100%	0 NaN	1 100%
White	0 0%	0 NaN	0 0%
More than one race	0 0%	0 NaN	0 0%
Unknown or Not Reported	0 0%	0 NaN	0 0%

Outcome Measures

1. Primary Outcome

Title	Safety and Efficacy Using Neo-adjuvant Gemcitabine Plus Nab-paclitaxel in Patients Receiving SBRT and Surgery for Borderline Resectable Pancreatic Cancer, Using Neo-adjuvant mFOLFIRINOX as a Control
Description	Efficacy: pathological complete response (pCR) and R0 resection. Safety: Grade 4 toxicity.
Time Frame	up to 5 years

Outcome Measure Data

Analysis Population Description

Patient did not receive three cycles of treatment - data were not collected.

Arm/Group Title	Gemcitabine/Nab-paclitaxel	mFOLFIRINOX
Arm/Group Description	Patients that received three cycles of treatment in the gemcitabine/nab-paclitaxel	Patients that received 6 cycles in the mFOLFIRINOX
Measure Participants	0	0

2. Secondary Outcome

Title	R0 Resection Rates in Borderline Resectable Pancreatic Cancer
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

Patient did not receive three cycles of treatment - data were not collected.

Arm/Group Title	Gemcitabine/Nab-paclitaxel	mFOLFIRINOX
Arm/Group Description	Patients that received three cycles of treatment in the gemcitabine/nab-paclitaxel	Patients that received 6 cycles in the mFOLFIRINOX
Measure Participants	0	0

3. Secondary Outcome

Title	Incidence of Grade 3 and 4 Toxicities for the 2 Chemotherapy Regimens That Occur After Cycle 1 Day 1
Description	According to the National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTAE, v4.0)
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

Patient was not treated - no data collected.

Arm/Group Title	Gemcitabine/Nab-paclitaxel	mFOLFIRINOX
Arm/Group Description	Patients that received three cycles of treatment in the gemcitabine/nab-paclitaxel	Patients that received 6 cycles in the mFOLFIRINOX
Measure Participants	0	0

4. Secondary Outcome

Title	Ca19-9 Response to Neoadjuvant Chemotherapy
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

Patient did not receive three cycles of treatment - data were not collected / zero total participants were analyzed.

Arm/Group Title	Gemcitabine/Nab-paclitaxel	mFOLFIRINOX
Arm/Group Description	three cycles of treatment in the gemcitabine/nab-paclitaxel gemcitabine/nab-paclitaxel: three cycles of treatment in the gemcitabine/nab-paclitaxel	6 cycles in the mFOLFIRINOX mFOLFIRINOX: 6 cycles in the mFOLFIRINOX
Measure Participants	0	0

5. Secondary Outcome

Title	Time to Disease Progression
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

Patient did not receive three cycles of treatment - data not collected.

Arm/Group Title	Gemcitabine/Nab-paclitaxel	mFOLFIRINOX
Arm/Group Description	Patients that received three cycles of treatment in the gemcitabine/nab-paclitaxel	Patients that received 6 cycles in the mFOLFIRINOX
Measure Participants	0	0

6. Secondary Outcome

Title	Measurement of Biomarkers (SPARC, RM1 and SMAD4) in Tissues
Description	This wil be measured in tissues that are obtained at screening and in the resected tumour specimen
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

Patient did not receive three cycles of treatment - data not collected.

Arm/Group Title	Gemcitabine/Nab-paclitaxel	mFOLFIRINOX
Arm/Group Description	Patients that received three cycles of treatment in the gemcitabine/nab-paclitaxel	Patients that received 6 cycles in the mFOLFIRINOX
Measure Participants	0	0

7. Secondary Outcome

Title	Radiological Response Rate to Therapy
Description	Radiological improvements will be evaluated by determining changes in density of measurable disease on CT scan pre and post chemotherapy
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

Patient did not receive three cycles of treatment - data not collected.

Arm/Group Title	Gemcitabine/Nab-paclitaxel	mFOLFIRINOX
Arm/Group Description	Patients that received three cycles of treatment in the gemcitabine/nab-paclitaxel	Patients that received 6 cycles in the mFOLFIRINOX
Measure Participants	0	0

8. Secondary Outcome

Title	Quality of Life Effects of Chemotherapy on Patients Receiving Chemotherapy and SBRT
Description	This will be measured using the FACT-HB questionaire
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

Patient did not receive three cycles of treatment - data not collected.

Arm/Group Title	Gemcitabine/Nab-paclitaxel	mFOLFIRINOX
Arm/Group Description	three cycles of treatment in the gemcitabine/nab-paclitaxel gemcitabine/nab-paclitaxel: three cycles of treatment in the gemcitabine/nab-paclitaxel	6 cycles in the mFOLFIRINOX mFOLFIRINOX: 6 cycles in the mFOLFIRINOX
Measure Participants	0	0

Adverse Events

Time Frame	6 months
Adverse Event Reporting Description	The number of participants at risk for Serious Adverse Events is zero for the Treatment Arm in which zero participants were treated. The number of participants at risk for Other (Not Including Serious) Adverse Events is zero for the Treatment Arm in which zero participants were treated. The number of participants at risk for All-Cause Mortality is zero for the Treatment Arm in which zero participants were treated.
Arm/Group Title	Gemcitabine/Nab-paclitaxel		mFOLFIRINOX
Arm/Group Description	Patients that received three cycles of treatment in the gemcitabine/nab-paclitaxel		Patients that received 6 cycles in the mFOLFIRINOX
All Cause Mortality
	Gemcitabine/Nab-paclitaxel		mFOLFIRINOX
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/1 (100%)		0/0 (NaN)
Serious Adverse Events
	Gemcitabine/Nab-paclitaxel		mFOLFIRINOX
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/1 (100%)		0/0 (NaN)
Musculoskeletal and connective tissue disorders
Myositis	1/1 (100%)	1	0/0 (NaN)	0
Other (Not Including Serious) Adverse Events
	Gemcitabine/Nab-paclitaxel		mFOLFIRINOX
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/0 (NaN)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.