A Randomized Phase II/Genomic Trial of Two Chemotherapy Regimens in Patients With Resected Pancreatic Adenocarcinoma

• Sponsor: Abramson Cancer Center of the University of Pennsylvania (Other)
• Overall Status: Completed
• CT.gov ID: NCT01839799
• Collaborator: (none)
• Enrollment: 32
• Location: 1
• Arms: 2
• Actual Duration (Months): 51
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

Determine the relapse-free survival of resected pancreatic cancer patients following two novel regimens with activity in advanced disease.

Condition or Disease	Intervention/Treatment	Phase
Pancreatic Adenocarcinoma	Drug: Gemcitabine; Drug: Abraxane; Drug: FOLFIRINOX; Radiation: Chemoradiation	Phase 2

Detailed Description

This trial is a randomized Phase II study of FOLFIRINOX versus gemcitabine/abraxane in patients with completely resected pancreatic cancer (Stages I-III). Patients will receive eight weeks of chemotherapy, then 5-FU/radiation, then another 8 weeks.

Study Design

• Study Type: Interventional
• Actual Enrollment: 32 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized Phase II/Genomic Trial of Two Chemotherapy Regimens in Patients With Resected Pancreatic Adenocarcinoma
• Actual Study Start Date: Apr 1, 2013
• Actual Primary Completion Date: Apr 1, 2017
• Actual Study Completion Date: Jul 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm 1 - FOLFIRINOX FOLFIRINOX: Irinotecan 180 mg/m2 Day 1 Oxaliplatin 85 mg/m2 Day 1 5-FU 400 mg/m2 bolus with Leucovorin 200 mg/m2 over 2h, Day 1, then 5-FU 2400 mg/m2 over 46h. Four cycles over 8 weeks Chemoradiation: Radiation to begin no sooner than 28 days from last day of chemotherapy. On Day 1(+ 2days to accommodate scheduling difficulties): Infusional 5-FU (225 mg/m2 continuous infusion during radiation) and radiation therapy as defined. FOLFIRINOX: Irinotecan 180 mg/m2 Day 1 Oxaliplatin 85 mg/m2 Day 1 5-FU 400 mg/m2 bolus with Leucovorin 200 mg/m2 over 2h, Day 1, then 5-FU 2400 mg/m2 over 46h. Four cycles, if tolerated	Drug: FOLFIRINOX; Irinotecan 180 mg/m2 Day 1 Oxaliplatin 85 mg/m2 Day 1 5-FU 400 mg/m2 bolus with Leucovorin 200 mg/m2 over 2h, Day 1, then 5-FU 2400 mg/m2 over 46h. Four cycles, if tolerated; Radiation: Chemoradiation
Experimental: Arm 2 - Gemcitabine / Abraxane Gemcitabine / Abraxane Gemcitabine 1000 mg/m2 Days 1, 8, 15 Abraxane 125 mg/m2 Days 1, 8, 15 Two cycles over 8 weeks Chemoradiation: Radiation to begin no sooner than 28 days from last day of chemotherapy. On Day 1 (+ 2days to accommodate scheduling difficulties) Infusional 5-FU (225 mg/m2 continuous infusion during radiation) and radiation therapy as defined. Gemcitabine / Abraxane Gemcitabine 1000 mg/m2 Days 1, 8, 15 Abraxane 125 mg/m2 Days 1, 8, 15 Two cycles, if tolerated	Drug: Gemcitabine; 1000mg/m2 IV over 30 to 100 minutes, day 1, 8, 15; Other Names: Gemzar ; Drug: Abraxane; 125 mg/m2 IV over 30 minutes, day 1, 8, 15; Other Names: Paclitaxel ; Radiation: Chemoradiation

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Relapse-free Survival [20 months]

   In this small trial we will regard a median progression-free survival of 20 months as indicative of potential therapeutic benefit meriting additional study.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Patients must have histologically or cytologically confirmed evidence of pancreatic carcinoma.

• Patients must have had all gross disease resected (R0 or R1 resection, patients who underwent an R2 resection are not eligible).

• Patients must have had no prior chemotherapy or radiation therapy for pancreatic cancer.

• Age > 18 years.

• Patient must have Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.

• Patients must have normal organ and marrow function measured within 2 weeks, prior to registration as follows:

Absolute Neutrophil Count (ANC) > 1,500/µL Platelets > 100,000/µL Total bilirubin less than 2-fold upper limit of normal (ULN) Aspartate Aminotransferase (AST)/alanine aminotransferase (ALT)<2.5X institutional upper limit of normal Creatinine clearance > 60mL/min for patients with creatinine levels above institutional normal.

• Patients must be > 4 weeks and < 12 weeks post-surgery at time of study registration.

• Women of childbearing potential and sexually active males are strongly advised to use appropriate contraceptive measures.

• Women must not be pregnant or breast-feeding.

Exclusion Criteria:

• Patients receiving any other investigational agents.

• Patients with known metastases.

• Patients with wounds that have not fully healed.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Abramson Cancer Center of the University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104

Sponsors and Collaborators

• Abramson Cancer Center of the University of Pennsylvania

Investigators

• Principal Investigator: Peter O'Dwyer, MD, Abramson Cancer Center of the University of Pennsylvania

Study Documents (Full-Text)

• Informed Consent Form - Mar 10, 2016
• Study Protocol and Statistical Analysis Plan - Feb 18, 2016

More Information

Publications

None provided.

• Responsible Party: Abramson Cancer Center of the University of Pennsylvania
• ClinicalTrials.gov Identifier: NCT01839799
• Other Study ID Numbers: UPCC 03213
• First Posted: Apr 25, 2013
• Last Update Posted: Feb 25, 2021
• Last Verified: Feb 1, 2021

• Keywords provided by Abramson Cancer Center of the University of Pennsylvania: Patients; with; resected
• Additional relevant MeSH terms: Adenocarcinoma; Gemcitabine; Paclitaxel; Albumin-Bound Paclitaxel; Folfirinox

Study Results

Participant Flow

Arm/Group Title	FOLFIRINOX	Gemcitabine/Abraxane
Arm/Group Description	FOLFIRINOX: Irinotecan 180 mg/m2 Day 1 Oxaliplatin 85 mg/m2 Day 1 5-FU 400 mg/m2 bolus with Leucovorin 200 mg/m2 over 2h, Day 1, then 5-FU 2400 mg/m2 over 46h. Four cycles, if tolerated Chemoradiation	Gemcitabine: 1000mg/m2 IV over 30 to 100 minutes, day 1, 8, 15 Abraxane: 125 mg/m2 IV over 30 minutes, day 1, 8, 15 Chemoradiation
Period Title: Overall Study
STARTED	17	15
COMPLETED	17	15
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	FOLFIRINOX	Gemcitabine	Total
Arm/Group Description	FOLFIRINOX: Irinotecan 180 mg/m2 Day 1 Oxaliplatin 85 mg/m2 Day 1 5-FU 400 mg/m2 bolus with Leucovorin 200 mg/m2 over 2h, Day 1, then 5-FU 2400 mg/m2 over 46h. Four cycles, if tolerated Chemoradiation	Gemcitabine: 1000mg/m2 IV over 30 to 100 minutes, day 1, 8, 15 Abraxane: 125 mg/m2 IV over 30 minutes, day 1, 8, 15 Chemoradiation	Total of all reporting groups
Overall Participants	17	15	32
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	6 35.3%	7 46.7%	13 40.6%
>=65 years	11 64.7%	8 53.3%	19 59.4%
Sex: Female, Male (Count of Participants)
Female	10 58.8%	5 33.3%	15 46.9%
Male	7 41.2%	10 66.7%	17 53.1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 5.9%	1 6.7%	2 6.3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 5.9%	1 6.7%	2 6.3%
White	13 76.5%	13 86.7%	26 81.3%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	2 11.8%	0 0%	2 6.3%
Region of Enrollment (participants) [Number]
United States	17 100%	15 100%	32 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Relapse-free Survival
Description	In this small trial we will regard a median progression-free survival of 20 months as indicative of potential therapeutic benefit meriting additional study.
Time Frame	20 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm 1	Arm 2
Arm/Group Description	FOLFIRINOX: Irinotecan 180 mg/m2 Day 1 Oxaliplatin 85 mg/m2 Day 1 5-FU 400 mg/m2 bolus with Leucovorin 200 mg/m2 over 2h, Day 1, then 5-FU 2400 mg/m2 over 46h. Four cycles, if tolerated Chemoradiation	Gemcitabine: 1000mg/m2 IV over 30 to 100 minutes, day 1, 8, 15 Abraxane: 125 mg/m2 IV over 30 minutes, day 1, 8, 15 Chemoradiation
Measure Participants	17	15
Count of Participants [Participants]	3 17.6%	2 13.3%

Adverse Events

Time Frame	2 years
Arm/Group Title	Arm 1		Arm 2
Arm/Group Description	FOLFIRINOX: Irinotecan 180 mg/m2 Day 1 Oxaliplatin 85 mg/m2 Day 1 5-FU 400 mg/m2 bolus with Leucovorin 200 mg/m2 over 2h, Day 1, then 5-FU 2400 mg/m2 over 46h. Four cycles, if tolerated Chemoradiation		Gemcitabine: 1000mg/m2 IV over 30 to 100 minutes, day 1, 8, 15 Abraxane: 125 mg/m2 IV over 30 minutes, day 1, 8, 15 Chemoradiation
All Cause Mortality
	Arm 1		Arm 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/17 (0%)		0/15 (0%)
Serious Adverse Events
	Arm 1		Arm 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/17 (23.5%)		6/15 (40%)
Blood and lymphatic system disorders
Thrombocytopenia	1/17 (5.9%)		0/15 (0%)
Neutropenia	1/17 (5.9%)		1/15 (6.7%)
Gastrointestinal disorders
anemia	1/17 (5.9%)		0/15 (0%)
GI Bleed	1/17 (5.9%)		0/15 (0%)
Gastric Ulcer	1/17 (5.9%)		0/15 (0%)
Nausea	3/17 (17.6%)		0/15 (0%)
Vomiting	3/17 (17.6%)		0/15 (0%)
Diarrhea	3/17 (17.6%)		0/15 (0%)
Septic Shock	0/17 (0%)		1/15 (6.7%)
SmBowel Obstruction	0/17 (0%)		1/15 (6.7%)
General disorders
Fever	4/17 (23.5%)		1/15 (6.7%)
Non-neutropenic fever	1/17 (5.9%)		0/15 (0%)
Chills	0/17 (0%)		1/15 (6.7%)
Fever /+ blood culture	0/17 (0%)		1/15 (6.7%)
Infections and infestations
Viral Syndrome	1/17 (5.9%)		0/15 (0%)
hepatic infection (SAE)	1/17 (5.9%)		0/15 (0%)
Bacteremia-E.Coli	0/17 (0%)		1/15 (6.7%)
CMV	1/17 (5.9%)		0/15 (0%)
Investigations
decrease wbc	2/17 (11.8%)		0/15 (0%)
decreased neutrophils	1/17 (5.9%)		0/15 (0%)
Metabolism and nutrition disorders
Dehydration	1/17 (5.9%)		0/15 (0%)
increased abd distention	1/17 (5.9%)		0/15 (0%)
protein malnutrition	1/17 (5.9%)		0/15 (0%)
decreased appetite	1/17 (5.9%)		0/15 (0%)
Musculoskeletal and connective tissue disorders
Abdominal pain	2/17 (11.8%)		0/15 (0%)
Bilatteral Hip Pain	0/17 (0%)		1/15 (6.7%)
Nervous system disorders
Syncope	1/17 (5.9%)		0/15 (0%)
PRESS	0/17 (0%)		1/15 (6.7%)
Other (Not Including Serious) Adverse Events
	Arm 1		Arm 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/17 (100%)		15/15 (100%)
Blood and lymphatic system disorders
anemia	2/17 (11.8%)		0/15 (0%)
Ear and labyrinth disorders
Ear Bleed -L-ear	1/17 (5.9%)		0/15 (0%)
Eye disorders
blurred vision	0/17 (0%)		0/15 (0%)
Myalgia	1/17 (5.9%)		0/15 (0%)
Tunnel Vision	1/17 (5.9%)		0/15 (0%)
Gastrointestinal disorders
nausea	13/17 (76.5%)		5/15 (33.3%)
diarrhea	14/17 (82.4%)		7/15 (46.7%)
vomiting	10/17 (58.8%)		3/15 (20%)
dry mouth	0/17 (0%)		0/15 (0%)
constipation	4/17 (23.5%)		3/15 (20%)
loose stools/intermittent	1/17 (5.9%)		2/15 (13.3%)
Dyspepsia	1/17 (5.9%)		0/15 (0%)
Loose bowel movement	1/17 (5.9%)		0/15 (0%)
gas	5/17 (29.4%)		6/15 (40%)
flatulance	1/17 (5.9%)		4/15 (26.7%)
stomach virus	0/17 (0%)		2/15 (13.3%)
General disorders
fatigue	14/17 (82.4%)		13/15 (86.7%)
edema	0/17 (0%)		6/15 (40%)
Dizziness	2/17 (11.8%)		0/15 (0%)
fever	5/17 (29.4%)		4/15 (26.7%)
gout	1/17 (5.9%)		0/15 (0%)
Lightheadeness	1/17 (5.9%)		0/15 (0%)
night sweats	1/17 (5.9%)		0/15 (0%)
Cold Sensitivity	1/17 (5.9%)		0/15 (0%)
orthostatic	0/17 (0%)		1/15 (6.7%)
Flu like symptoms	0/17 (0%)		3/15 (20%)
Chills	0/17 (0%)		1/15 (6.7%)
Fever Other	0/17 (0%)		3/15 (20%)
Infections and infestations
paronychia	1/17 (5.9%)		0/15 (0%)
Investigations
elevated ALK Phos	1/17 (5.9%)		0/15 (0%)
elevated creatinine	0/17 (0%)		0/15 (0%)
elevated trigylcerides	0/17 (0%)		0/15 (0%)
thrombocytopenia	1/17 (5.9%)		1/15 (6.7%)
elevated ALT	0/17 (0%)		4/15 (26.7%)
hyperkalemia	0/17 (0%)		0/15 (0%)
elevated cholesterol	0/17 (0%)		0/15 (0%)
hypoalbuminemia	2/17 (11.8%)		0/15 (0%)
weight loss	3/17 (17.6%)		1/15 (6.7%)
hyperglycemia	4/17 (23.5%)		0/15 (0%)
hypokalemia	5/17 (29.4%)		1/15 (6.7%)
hyponatremia	0/17 (0%)		0/15 (0%)
neutropenia	10/17 (58.8%)		10/15 (66.7%)
decreased wbc	5/17 (29.4%)		4/15 (26.7%)
hypomagnesium	1/17 (5.9%)		0/15 (0%)
Decreased Platlets	3/17 (17.6%)		1/15 (6.7%)
increased Ast	1/17 (5.9%)		0/15 (0%)
decreased plt	3/17 (17.6%)		1/15 (6.7%)
hypotension	2/17 (11.8%)		2/15 (13.3%)
decreased neutrophils	3/17 (17.6%)		0/15 (0%)
protein malnutrition	1/17 (5.9%)		0/15 (0%)
decrease wbc	1/17 (5.9%)		4/15 (26.7%)
Decreased Appetite	2/17 (11.8%)		1/15 (6.7%)
elevated AST	0/17 (0%)		6/15 (40%)
Metabolism and nutrition disorders
anorexia	3/17 (17.6%)		1/15 (6.7%)
dehydration	6/17 (35.3%)		0/15 (0%)
malabsorption	0/17 (0%)		1/15 (6.7%)
Musculoskeletal and connective tissue disorders
abd/cramping/pain	1/17 (5.9%)		1/15 (6.7%)
abdominal pain	5/17 (29.4%)		3/15 (20%)
abdominal cramping	1/17 (5.9%)		0/15 (0%)
Muscle twitching	1/17 (5.9%)		0/15 (0%)
Thick feeling tongue	1/17 (5.9%)		0/15 (0%)
Chest Pressure/Spasm	1/17 (5.9%)		0/15 (0%)
Nervous system disorders
headache	1/17 (5.9%)		1/15 (6.7%)
dysgeusia	2/17 (11.8%)		1/15 (6.7%)
peripheral neuropathy	2/17 (11.8%)		1/15 (6.7%)
neuropathy	7/17 (41.2%)		4/15 (26.7%)
siatica	0/17 (0%)		1/15 (6.7%)
Psychiatric disorders
Insomnia	3/17 (17.6%)		1/15 (6.7%)
Anxiety	2/17 (11.8%)		0/15 (0%)
Depression	2/17 (11.8%)		0/15 (0%)
Renal and urinary disorders
UTI	3/17 (17.6%)		1/15 (6.7%)
Urinary Incontinence	1/17 (5.9%)		0/15 (0%)
Respiratory, thoracic and mediastinal disorders
mucositis	6/17 (35.3%)		2/15 (13.3%)
hiccoughs	1/17 (5.9%)		0/15 (0%)
Nasal Congestion	1/17 (5.9%)		0/15 (0%)
Horseness	0/17 (0%)		1/15 (6.7%)
Skin and subcutaneous tissue disorders
rash	3/17 (17.6%)		4/15 (26.7%)
dry skin	1/17 (5.9%)		0/15 (0%)
pruritis	0/17 (0%)		0/15 (0%)
skin infection port	1/17 (5.9%)		0/15 (0%)
Runny nose	1/17 (5.9%)		0/15 (0%)
Mouth Sores	6/17 (35.3%)		1/15 (6.7%)
Alopecia	2/17 (11.8%)		6/15 (40%)
ratiation dermatitis	1/17 (5.9%)		0/15 (0%)
hypersensitivity reaction	1/17 (5.9%)		0/15 (0%)
Soft nails	0/17 (0%)		1/15 (6.7%)
folliculitis	0/17 (0%)		1/15 (6.7%)

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.