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

Stage IV Colorectal Cancer Clinical Trial

Official title:

Phase I/II Study of Intravenous Ascorbic Acid in Combination With Irinotecan Versus Irinotecan Alone for Advanced Colorectal Cancer

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01550510
• Other study ID #: 11D.459
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: December 2011
• Est. completion date: February 2015

Study information

• Verified date: June 2020
• Source: Thomas Jefferson University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 4
• Est. completion date: February 2015
• Est. primary completion date: February 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Stage IV Colorectal Cancer

Intervention

Drug:
• Ascorbic Acid
3x a week for 9 weeks
• Irinotecan
350mg/m2 once a week every 3 weeks

Locations

Country	Name	City	State
United States	Thomas Jefferson University	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Thomas Jefferson University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants That Experience Serious Adverse Events as Defined by the Common Terminology Criteria for Adverse Events (CTCAE) v4.0.	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.	9 weeks +/- 2 weeks
Secondary	Number of Participants That Are Alive After 11 Weeks.	To evaluate progression-free survival related to treatment of patients with advanced or recurrent colorectal cancer	9 weeks +/- 2 weeks

External Links

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