Ascorbic Acid and Combination Chemotherapy in Treating Patients With Locally Advanced or Recurrent Pancreatic Cancer That Cannot Be Removed by Surgery

• Sponsor: Sidney Kimmel Cancer Center at Thomas Jefferson University (Other)
• Overall Status: Completed
• CT.gov ID: NCT02896907
• Collaborator: (none)
• Enrollment: 8
• Location: 1
• Arm: 1
• Actual Duration (Months): 28.4
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This pilot clinical trial studies the side effects of ascorbic acid and combination chemotherapy in treating patients with pancreatic cancer that has spread to other places in the body, has come back, or cannot be removed by surgery. Nutrients found in food and dietary supplements, such as ascorbic acid, may improve the tolerability of chemotherapy regimens. Drugs used in chemotherapy, such as fluorouracil, irinotecan hydrochloride, and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving ascorbic acid and combination chemotherapy may work better in treating patients with pancreatic cancer.

Condition or Disease	Intervention/Treatment	Phase
Pancreatic Adenocarcinoma; Recurrent Pancreatic Carcinoma; Stage III Pancreatic Cancer; Stage IV Pancreatic Cancer; Unresectable Pancreatic Carcinoma	Drug: Oxaliplatin; Drug: Irinotecan Hydrochloride; Drug: Leucovorin Calcium; Drug: Fluorouracil; Dietary Supplement: Ascorbic Acid	Early Phase 1

Detailed Description

PRIMARY OBJECTIVES:

1. To determine safety of intravenous ascorbic acid in combination with fluorouracil, irinotecan hydrochloride, leucovorin calcium, and oxaliplatin (FOLFIRINOX) as defined by Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 in patients with advanced pancreatic cancer.

SECONDARY OBJECTIVES:

1. To test feasibility of collecting quality of life (QOL), patient reported outcomes (PRO) data and correlative studies on patients with advanced pancreatic cancer.

Study Design

• Study Type: Interventional
• Actual Enrollment: 8 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Pilot Study of Intravenous Ascorbic Acid and Folfirinox in the Treatment of Advanced Pancreatic Cancer
• Actual Study Start Date: Oct 18, 2016
• Actual Primary Completion Date: Mar 22, 2018
• Actual Study Completion Date: Mar 1, 2019

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Treatment (FOLFIRINOX, ascorbic acid) Patients receive oxaliplatin IV over 2 hours, irinotecan hydrochloride IV over 90 minutes, leucovorin calcium IV over 2 hours, and fluorouracil IV continuously over 46 hours on day 1. Patients then receive ascorbic acid IV over 2 hours on days 3, 5, 8, 10 and 12. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

Drug: Oxaliplatin; Given IV; Other Names: Diaminocyclohexane Oxalatoplatinum Eloxatin Dacotin Dacplat 61825-94-3 [(1R,-2R)-1,2-cyclohexanediamine-N,N'][oxalato (2--)-O,O']platinum [Sp-4-2-(1R-trans)]-(1,2,cyclohexanediamine-N,N')[ethanedioato(2--)-O,O']platinum Ai Heng Oxalatoplatin trans-l diaminocyclohexane oxalatoplatinum ; Drug: Irinotecan Hydrochloride; Given IV; Other Names: 136572-09-3 Campto Camptosar Camptothecin 11 ; Drug: Leucovorin Calcium; Given IV; Other Names: 1492-18-8 3590 5-Formyl Tetrahydrofolate 5-Formyl-5,6,7,8-tetrahydrofolic Acid 5-Formyl-5,6,7,8-tetrahydropteroyl-L-glutamic Acid Adinepar Calcifolin Calcium (6S)-Folinate Calcium Folinate Calcium N-(p-((((6RS)-2-amino-5-formyl-5,6,7,8-tetrahydro-4-hydroxy-6-pteridinyl)methyl)amino)benzoyl)-L-glutamate (1:1) Calfolex Calinat Cehafolin Citofolin Citrec Citrovorum Factor Cromatonbic Folinico Dalisol Disintox Divical Ecofol Emovis Flynoken A Folaren Folaxin Foliben Folinic Acid Calcium Salt Pentahydrate Folix Lederfolin Leucosar N-[4-[[(2-Amino-5-formyl-1,4,5,6,7,8-hexahydro-4-oxo-6-pteridinyl)methyl]amnio]benzoyl]-L-glutamic Acid Rescufolin Tonofolin Rescuvolin Wellcovorin ; Drug: Fluorouracil; Given IV; Other Names: 19893 2,4-Dioxo-5-fluoropyrimidine 5-Fluoro-2,4(1H, 3H)-pyrimidinedione 5-Fluorouracil AccuSite Fluracedyl Fluracil Fluroblastin Ribofluor Ro 2-9757 ; Dietary Supplement: Ascorbic Acid; Given IV; Other Names: 2-(1,2-dihydroxyethyl)-4,5-dihydroxy-furan-3-one 33832 50-81-7 Asorbicap C Vitamin C-Long Ce-Vi-Sol Cecon Cenolate L-Ascorbic Acid Vitamin C

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Adverse Events as Determined by CTCAE Version 4.03 [Up to 28 days after the last treatment]

   After 4 patients are enrolled on the study and receive at least one dose of intravenous ascorbic acid, the data will be reviewed. If 2 out of the 4 cannot complete 2 courses of FOLFIRINOX then the study will be halted.

Secondary Outcome Measures

1. Change in Quality of Life as Defined by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C-30 [Baseline to up to 28 days after the last treatment]

   Change in quality of life over the six measurement times will be modeled using mixed effects linear regression to account for correlation among repeated measurements from the same subjects. Average change in QoL from baseline to follow-up will be computed.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Capable of giving informed consent

• Histological diagnosis of adenocarcinoma of the pancreas

• Stage IV or recurrent pancreatic cancer by imaging

• Locally advanced unresectable pancreatic cancer by National Comprehensive Cancer Network (NCCN) criteria

• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1

• No prior treatment for metastatic disease (prior neo-adjuvant or adjuvant chemotherapy, except FOLFIRINOX, chemoradiation or radiation allowed)

• White blood count >= 3000

• Platelets >= 100,000

• Total bilirubin =< 1.5 mg/dl

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 5 X upper limit of normal (ULN)

• Creatinine < 1.5 mg/dL

• Glucose-6-phosphatase deficiency (G6PD) level of 5-14 units/g hemoglobin (Hgb) or within institutional standard parameters

• All subjects of child producing potential must agree to use contraception or avoidance of pregnancy measures while enrolled on study

Exclusion Criteria:

• Other pancreatic cancer histology (islet cell, acinar, neuroendocrine tumors)

• Resectable pancreatic cancer

• Prior neoadjuvant FOLFIRINOX

• Pregnant or lactating females

• No clinical ascites (mild ascites on scans permissible)

• Central nervous system (CNS) metastasis

• Known congestive heart failure, significant ventricular arrhythmias, cirrhosis, grade 4/5 chronic kidney disease, uncontrolled diabetes

• Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy

• Peripheral neuropathy grade 2 or greater

• Any condition, psychiatric or otherwise, that would preclude informed consent, consistent follow-up or compliance with any aspect of the study (e.g., untreated schizophrenia or other significant cognitive impairment, etc.)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sidney Kimmel Cancer Center at Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19107

Sponsors and Collaborators

• Sidney Kimmel Cancer Center at Thomas Jefferson University

Investigators

• Principal Investigator: James Posey, MD, Sidney Kimmel Cancer Center at Thomas Jefferson University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Aug 28, 2017

More Information

Additional Information:

• Sidney Kimmel Cancer Center at Thomas Jefferson University, an NCI-Designated Cancer Center
• Thomas Jefferson University Hospital

Publications

None provided.

• Responsible Party: Sidney Kimmel Cancer Center at Thomas Jefferson University
• ClinicalTrials.gov Identifier: NCT02896907
• Other Study ID Numbers: 16D.347
• First Posted: Sep 12, 2016
• Last Update Posted: Jan 18, 2020
• Last Verified: Jan 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Additional relevant MeSH terms: Carcinoma; Pancreatic Neoplasms; Calcium, Dietary; Vitamins; Leucovorin; Ascorbic Acid; Formyltetrahydrofolates; Tetrahydrofolates; Fluorouracil; Oxaliplatin; Irinotecan; Camptothecin; Calcium; Levoleucovorin

Study Results

Participant Flow

Arm/Group Title	Treatment (FOLFIRINOX, Ascorbic Acid)
Arm/Group Description	Patients receive oxaliplatin IV over 2 hours, irinotecan hydrochloride IV over 90 minutes, leucovorin calcium IV over 2 hours, and fluorouracil IV continuously over 46 hours on day 1. Patients then receive ascorbic acid IV over 2 hours on days 3, 5, 8, 10 and 12. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. Oxaliplatin: Given IV Irinotecan Hydrochloride: Given IV Leucovorin Calcium: Given IV Fluorouracil: Given IV Ascorbic Acid: Given IV
Period Title: Overall Study
STARTED	8
COMPLETED	8
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Treatment (FOLFIRINOX, Ascorbic Acid)
Arm/Group Description	Patients receive oxaliplatin IV over 2 hours, irinotecan hydrochloride IV over 90 minutes, leucovorin calcium IV over 2 hours, and fluorouracil IV continuously over 46 hours on day 1. Patients then receive ascorbic acid IV over 2 hours on days 3, 5, 8, 10 and 12. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. Oxaliplatin: Given IV Irinotecan Hydrochloride: Given IV Leucovorin Calcium: Given IV Fluorouracil: Given IV Ascorbic Acid: Given IV
Overall Participants	8
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	7 87.5%
>=65 years	1 12.5%
Sex: Female, Male (Count of Participants)
Female	6 75%
Male	2 25%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 12.5%
Not Hispanic or Latino	7 87.5%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	3 37.5%
White	5 62.5%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	8 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Adverse Events as Determined by CTCAE Version 4.03
Description	After 4 patients are enrolled on the study and receive at least one dose of intravenous ascorbic acid, the data will be reviewed. If 2 out of the 4 cannot complete 2 courses of FOLFIRINOX then the study will be halted.
Time Frame	Up to 28 days after the last treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (FOLFIRINOX, Ascorbic Acid)
Arm/Group Description	Patients receive oxaliplatin IV over 2 hours, irinotecan hydrochloride IV over 90 minutes, leucovorin calcium IV over 2 hours, and fluorouracil IV continuously over 46 hours on day 1. Patients then receive ascorbic acid IV over 2 hours on days 3, 5, 8, 10 and 12. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. Oxaliplatin: Given IV Irinotecan Hydrochloride: Given IV Leucovorin Calcium: Given IV Fluorouracil: Given IV Ascorbic Acid: Given IV
Measure Participants	8
Grade 4 adverse event	1 12.5%
Grade 5 adverse event	1 12.5%
Grade 3 adverse event	4 50%
No Serious Adverse Events	2 25%

2. Secondary Outcome

Title	Change in Quality of Life as Defined by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C-30
Description	Change in quality of life over the six measurement times will be modeled using mixed effects linear regression to account for correlation among repeated measurements from the same subjects. Average change in QoL from baseline to follow-up will be computed.
Time Frame	Baseline to up to 28 days after the last treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (FOLFIRINOX, Ascorbic Acid)
Arm/Group Description	Patients receive oxaliplatin IV over 2 hours, irinotecan hydrochloride IV over 90 minutes, leucovorin calcium IV over 2 hours, and fluorouracil IV continuously over 46 hours on day 1. Patients then receive ascorbic acid IV over 2 hours on days 3, 5, 8, 10 and 12. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. Oxaliplatin: Given IV Irinotecan Hydrochloride: Given IV Leucovorin Calcium: Given IV Fluorouracil: Given IV Ascorbic Acid: Given IV
Measure Participants	8
Mean (Standard Deviation) [score on a scale]	NA (NA)

Adverse Events

Time Frame	baseline through 30 days after completing treatment; an average of 4 months.
Arm/Group Title	Treatment (FOLFIRINOX, Ascorbic Acid)
Arm/Group Description	Patients receive oxaliplatin IV over 2 hours, irinotecan hydrochloride IV over 90 minutes, leucovorin calcium IV over 2 hours, and fluorouracil IV continuously over 46 hours on day 1. Patients then receive ascorbic acid IV over 2 hours on days 3, 5, 8, 10 and 12. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. Oxaliplatin: Given IV Irinotecan Hydrochloride: Given IV Leucovorin Calcium: Given IV Fluorouracil: Given IV Ascorbic Acid: Given IV
All Cause Mortality
	Treatment (FOLFIRINOX, Ascorbic Acid)
	Affected / at Risk (%)	# Events
Total	6/8 (75%)
Serious Adverse Events
	Treatment (FOLFIRINOX, Ascorbic Acid)
	Affected / at Risk (%)	# Events
Total	6/8 (75%)
Blood and lymphatic system disorders
Sepsis	1/8 (12.5%)
Anemia	3/8 (37.5%)
Neutropenia	1/8 (12.5%)
General disorders
Hypokalemia	4/8 (50%)
Respiratory, thoracic and mediastinal disorders
Pleural Effusion	1/8 (12.5%)
Other (Not Including Serious) Adverse Events
	Treatment (FOLFIRINOX, Ascorbic Acid)
	Affected / at Risk (%)	# Events
Total	0/8 (0%)

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.