Research Study of IV Vitamin C in Combination With Irinotecan vs Irinotecan Alone for Advanced Colorectal CA

• Sponsor: Thomas Jefferson University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01550510
• Collaborator: (none)
• Enrollment: 4
• Location: 1
• Arms: 2
• Duration (Months): 38
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This protocol is a phase I/II, study of ascorbic acid (AA) infusions combined with treatment with irinotecan versus treatment with irinotecan alone in patients with recurrent or advanced colorectal cancer who have failed at least one treatment regimen with a 5-FU based therapy. This study will be conducted as an amendment to Investigational New Drug # 77486.

Condition or Disease	Intervention/Treatment	Phase
Stage IV Colorectal Cancer	Drug: Ascorbic Acid; Drug: Irinotecan	Phase 1/Phase 2

Detailed Description

Phase I: To assess whether or not (IV) Ascorbic Acid (AA) with irinotecan therapy is relatively safe and well-tolerated. This aim will be assessed by enrolling a minimum of 6 subjects meeting inclusion criteria, using a modified 3+3 design. Safety will be assessed with the following: toxicity graded by the NCI CTC, urinalysis pre- and post-infusion, basic metabolic panel, and CBC. From our experience and in the experience of our study collaborators, we hypothesize that the combination of IV AA with irinotecan will not be associated with adverse events.

Phase II: To utilize CT or PET/CT (when available) scans to evaluate disease progression to assess overall tumor response rate (complete and partial response) in subjects with advanced or recurrent colorectal cancer treated with the combination of ascorbic acid and irinotecan versus irinotecan alone.

Study Design

• Study Type: Interventional
• Actual Enrollment: 4 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase I/II Study of Intravenous Ascorbic Acid in Combination With Irinotecan Versus Irinotecan Alone for Advanced Colorectal Cancer
• Study Start Date: Dec 1, 2011
• Actual Primary Completion Date: Feb 1, 2015
• Actual Study Completion Date: Feb 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ascorbic Acid + Irinotecan Ascorbic Acid (50-100g, 3x weekly) with 350mg/m2 irinotecan once a week every 3 weeks	Drug: Ascorbic Acid; 3x a week for 9 weeks; Other Names: Ascorbate Vitamin C ; Drug: Irinotecan; 350mg/m2 once a week every 3 weeks; Other Names: Camptothecin-11 CPT-11
Active Comparator: Standard of Care (irinotecan alone) 350mg/m2 irinotecan once a week every 3 weeks	Drug: Irinotecan; 350mg/m2 once a week every 3 weeks; Other Names: Camptothecin-11 CPT-11

Outcome Measures

Primary Outcome Measures

1. Number of Participants That Experience Serious Adverse Events as Defined by the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. [9 weeks +/- 2 weeks]

   Safety: The primary aim is to assess whether or not (IV) Ascorbic Acid (AA) with irinotecan therapy is relatively safe and well-tolerated according to Common Terminology Criteria for Adverse Events (CTCAE) v4.0.

Secondary Outcome Measures

1. Number of Participants That Are Alive After 11 Weeks. [9 weeks +/- 2 weeks]

   To evaluate progression-free survival related to treatment of patients with advanced or recurrent colorectal cancer

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Age > 18 years

• Metastatic colorectal carcinoma (stage IV disease).

• Patients must have progressed on one or more prior chemotherapy treatment regimens including at least one trial of a 5-FU/oxaliplatin based therapy (FOLFOX) in combination with bevacizumab. Patients must not have had standard chemotherapy within at least 2 weeks of beginning ascorbic acid treatment provided that they have recovered from any toxicities that they experienced.

• G6PD status > lower limit of normal

• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.

• Laboratory at baseline evaluation for inclusion in the study: creatinine ≤1.5X upper limit (if the creatinine is elevated, but ≤1.5X the ULN, a 24 hour creatinine clearance will be obtained); transaminase (AST/ALT) ≤2.0X upper limit of normal; bilirubin levels ≥ 2 mg/dL; ANC ≥1,500/mm3; Hemoglobin > 8g/dL; platelet ≥ 100,000/mm3;

• Women of childbearing potential will confirm a negative pregnancy test and must practice effective contraception during the study.

• Willing and able to provide informed consent and participate in the study procedures.

Exclusion Criteria:

• Patients with evidence of a significant current psychiatric disorder that would prevent completion of the study as determined by the PI will not be allowed to participate.

• Co-morbid medical condition that would affect survival or tolerance as determined by the PI. This includes patients who have not fully recovered from toxicities associated with prior therapy. It also includes subjects who, as determined by the PI, are at risk of experiencing fluid overload (i.e., congestive heart failure).

• Patients who currently abuse alcohol or drugs.

• Patients with known glomerular filtration rate of <60ml/min or with nephrotic range proteinuria.

• Pregnant or lactating women

• Enrollment in active clinical trial/ experimental therapy or IND study within the prior 30 days.

• Contraindication for CT or PET/CT as per the PI.

• Patients who are on strong inducers of CYP3A4 which include but are not limited to: Aminoglutethimide, Bexarotene, Bosentan, Carbamazepine, Dexamethasone, Efavirenz, Fosphenytoin, Griseofulvin, Modafinil, Nafcillin, Nevirapine, Oxcarbazepine, Phenobarbital, Phenytoin, Primidone, Rifabutin, Rifampin, Rifapentine, St. John's wort.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19107

Sponsors and Collaborators

• Thomas Jefferson University

Investigators

• Principal Investigator: Daniel A Monti, MD, Thomas Jefferson University

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Sidney Kimmel Cancer Center at Thomas Jefferson University
• Thomas Jefferson University Hospital

Publications

None provided.

• Responsible Party: Thomas Jefferson University
• ClinicalTrials.gov Identifier: NCT01550510
• Other Study ID Numbers: 11D.459
• First Posted: Mar 12, 2012
• Last Update Posted: Jul 13, 2020
• Last Verified: Jun 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Thomas Jefferson University: Stage IV Colorectal cancer; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Ascorbic Acid; Vitamins; Irinotecan; Integrative Medicine; Complementary Medicine; Alternative Medicine Antioxidants; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Protective Agents; Physiological Effects of Drugs; Micronutrients; Growth Substances; Antineoplastic Agents, Phytogenic; Antineoplastic Agents; Therapeutic Uses; Radiation-Sensitizing Agents; Topoisomerase I Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors
• Additional relevant MeSH terms: Colorectal Neoplasms; Ascorbic Acid; Irinotecan; Camptothecin

Study Results

Participant Flow

Arm/Group Title	Ascorbic Acid	Standard of Care (Irinotecan Alone)
Arm/Group Description	Ascorbic Acid (50-100g, 3x weekly) Ascorbic Acid: 3x a week for 9 weeks	350mg/m2 once a week every 3 weeks
Period Title: Overall Study
STARTED	4	0
COMPLETED	4	0
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Ascorbic Acid+Irinotecan	Standard of Care (Irinotecan Alone)	Total
Arm/Group Description	Ascorbic Acid (50-100g, 3x weekly) Ascorbic Acid: 3x a week for 9 weeks	350mg/m2 once a week every 3 weeks	Total of all reporting groups
Overall Participants	4	0	4
Age (Count of Participants)
<=18 years	0 0%	0 NaN
Between 18 and 65 years	1 25%	1 Infinity
>=65 years	3 75%	3 Infinity
Sex: Female, Male (Count of Participants)
Female	3 75%	3 Infinity
Male	1 25%	1 Infinity
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 NaN
Not Hispanic or Latino	4 100%	4 Infinity
Unknown or Not Reported	0 0%	0 NaN
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 NaN
Asian	0 0%	0 NaN
Native Hawaiian or Other Pacific Islander	0 0%	0 NaN
Black or African American	2 50%	2 Infinity
White	1 25%	1 Infinity
More than one race	0 0%	0 NaN
Unknown or Not Reported	1 25%	1 Infinity
Region of Enrollment (participants) [Number]
United States	4 100%	4 Infinity

Outcome Measures

1. Primary Outcome

Title	Number of Participants That Experience Serious Adverse Events as Defined by the Common Terminology Criteria for Adverse Events (CTCAE) v4.0.
Description	Safety: The primary aim is to assess whether or not (IV) Ascorbic Acid (AA) with irinotecan therapy is relatively safe and well-tolerated according to Common Terminology Criteria for Adverse Events (CTCAE) v4.0.
Time Frame	9 weeks +/- 2 weeks

Outcome Measure Data

Analysis Population Description

The study was closed early due to lack of accrual. The data were not collected or analyzed.

Arm/Group Title	Ascorbic Acid+Irinotecan	Standard of Care (Irinotecan Alone)
Arm/Group Description	Ascorbic Acid (50-100g, 3x weekly) Ascorbic Acid: 3x a week for 9 weeks	350mg/m2 once a week every 3 weeks
Measure Participants	0	0

2. Secondary Outcome

Title	Number of Participants That Are Alive After 11 Weeks.
Description	To evaluate progression-free survival related to treatment of patients with advanced or recurrent colorectal cancer
Time Frame	9 weeks +/- 2 weeks

Outcome Measure Data

Analysis Population Description

The study was closed early due to lack of accrual. The data were not collected or analyzed.

Arm/Group Title	Ascorbic Acid	Standard of Care (Irinotecan Alone)
Arm/Group Description	Ascorbic Acid (50-100g, 3x weekly) Ascorbic Acid: 3x a week for 9 weeks	350mg/m2 once a week every 3 weeks
Measure Participants	0	0

Adverse Events

Adverse Event Reporting Description	The study was closed early due to lack of accrual. Adverse event data were collected for the patients who were enrolled in the study.
Arm/Group Title	Ascorbic Acid+Irinotecan		Standard of Care (Irinotecan Alone)
Arm/Group Description	Ascorbic Acid (50-100g, 3x weekly) Ascorbic Acid: 3x a week for 9 weeks		350mg/m2 once a week every 3 weeks
All Cause Mortality
	Ascorbic Acid+Irinotecan		Standard of Care (Irinotecan Alone)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0%)		0/0 (NaN)
Serious Adverse Events
	Ascorbic Acid+Irinotecan		Standard of Care (Irinotecan Alone)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0%)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Ascorbic Acid+Irinotecan		Standard of Care (Irinotecan Alone)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/4 (50%)		0/0 (NaN)
Blood and lymphatic system disorders
Hypokalemia	1/4 (25%)	1	1/0 (Infinity)	1
Low Hemoglobin	1/4 (25%)	1	1/0 (Infinity)	1

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.