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ARM A subjects will receive atorvastatin 20 mg orally once daily given for two weeks prior to FOLFIRI. The last dose of atorvastatin will be taken day 1 of FOLFIRI. ARM A will then receive no statin for the next 2 weeks. Patients will receive FOLFIRI infusion on day 1 and day 15. Blood samples will be collected at baseline and periodically through 24 hours on day 1 and 15 of FOLFIRI.

ARM B subjects will receive no atorvastatin prior to day 1 of FOLFIRI. ARM B subjects will receive atorvastatin 20 mg orally once daily for two weeks prior to day 15 of FOLFIRI. The last dose of atorvastatin will be taken day 15 of FOLFIRI. Patients will receive FOLFIRI infusion on day 1 and day 15. Blood samples will be collected at baseline and periodically through 24 hours on day 1 and 15 of FOLFIRI.

All patients will receive FOLFIRI infusion on day 1 and day 15.

FOLFIRI.

A subjects will receive atorvastatin 20 mg orally once daily given for two weeks starting on Day -14 during PERIOD ONE. ARM A will then receive no statin during PERIOD TWO. ARM B subjects will receive no atorvastatin during PERIOD ONE. ARM B subjects will receive atorvastatin 20 mg orally once daily for two weeks during PERIOD TWO (starting on Day 2). One cycle = 28 days.

Autumn McRee, MD

The purpose of this study is to evaluate the effect of atorvastatin on the pharmacokinetic profile of irinotecan and SN-38. To further evaluate the safety of atorvastatin in combination with FOLFIRI. To further evaluate the safety and of irinotecan in combination with atorvastatin.

This is a single-center, prospective, randomized, crossover study to address the pharmacokinetic effects of atorvastatin on irinotecan metabolism in patients receiving their first cycle of FOLFIRI (5-fluorouracil + leucovorin + irinotecan).

Each cycle of FOLFIRI is defined as 28 days, with a dose of FOLFIRI administered on day 1 and day 15. Patients will be recruited from the UNC Lineberger Cancer Center, referred by their primary oncologist for the treatment of metastatic colorectal cancer (mCRC). After obtaining informed consent, the patient will be randomized to either ARM A or ARM B.

Blood samples will be collected on day 1 and 15 of FOLFIRI prior to treatment with irinotecan (baseline), immediately following the end of the irinotecan infusion, and at 0.5, 1, 1.5, 2, 4, 6, and 24 hours following the end of the irinotecan infusion.

ARM A subjects will receive atorvastatin 20 mg orally once daily given for two weeks starting on Day -14 during PERIOD ONE. ARM A will then receive no statin during PERIOD TWO. Patients will receive FOLFIRI infusion on day 1 and day 15. Blood samples will be collected at baseline and periodically through 24 hours.

ARM B subjects will receive no atorvastatin during PERIOD ONE. ARM B subjects will receive atorvastatin 20 mg orally once daily for two weeks during PERIOD TWO (starting on Day 2). Patients will receive FOLFIRI infusion on day 1 and day 15. Blood samples will be collected at baseline and periodically through 24 hours.

DNA extraction and genetic analysis of UGT1A1 polymorphisms will be performed in collaboration with Dr. Federico Innocenti and those patients homozygous for the UGT1A1\*28 allele will be excluded due to their altered irinotecan metabolism.

Patients will be followed until Day 1 of Cycle 2 of FOLFIRI. Patients removed from study for unacceptable adverse events will be followed until resolution or stabilization of the event(s).

Crossover Evaluation of Effect of Atorvastatin on PK of Irinotecan in CRC Patients Receiving FOLFIRI

A Prospective, Randomized, Crossover Evaluation of the Effect of Atorvastatin on the Pharmacokinetics of Irinotecan in Colorectal Cancer Patients Receiving FOLFIRI

At the end of the screening period, eligible patients will be randomly assigned in a 1:1 ratio to receive atorvastatin prior to Day 1 of FOLFIRI (ARM A) or atorvastatin prior to Day 15 FOLFIRI (ARM B). Patients in ARM A must start atorvastatin within 28 days of randomization and patients in ARM B should receive FOLFIRI within 28 days of randomization; if not, the Investigator must be notified.

UNC Lineberger Comprehensive Cancer Center

Digestive System Diseases

Rectal Neoplasms

Colonic Neoplasms

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

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Rectal Diseases

Colonic Diseases

Molgramostim

Sargramostim

Granulocyte-macrophage colony-stimulating factor (GM-CSF) 250ug/m\^2 SQ QD with a cap of 500mcg SQ QD

250ug/m\^2 SQ QD with a cap of 500mcg SQ QD

GM-CSF

Randall Holcombe, MD

While new treatments for metastatic and recurrent colorectal cancer have become available over the past several years, this disease remains incurable with a limited life expectancy from the time of diagnosis. New strategies for treatment of disseminated colorectal cancer are needed. Under this proposal, patients with advanced colorectal cancer will receive Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) to stimulate endogenous dendritic cells and enhance anti-tumor immune mechanisms. This will be combined with standard chemotherapy and patients will be followed for response and overall survival. Detailed correlative laboratory analysis will also be performed to define the extent of dendritic cell and cellular immune system stimulation.

Cellular Immune Augmentation in Colon and Rectal Cancer

A Pilot Study of Cellular Immune Augmentation in Colon and Rectal Cancer Therapy

Immunological dendritic cell and cellular immune responses to GM-CSF administered in conjunction with chemotherapy for patients with advanced colorectal cancer.

Effect of cellular immune stimulation on response rates and overall survival. This is a secondary endpoint and while data will be recorded, a larger study with improved power will be necessary to confirm any improvements noted.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Crossover Evaluation of Effect of Atorvastatin on PK of Irinotecan in CRC Patients Receiving FOLFIRI	NCT01605344	Advanced Adenoc...	FOLFIRI. Atorvastatin	18 Years -	UNC Lineberger Comprehensive Cancer Center
Crossover Evaluation of Effect of Atorvastatin on PK of Irinotecan in CRC Patients Receiving FOLFIRI	NCT01605344	Advanced Adenoc...	FOLFIRI. Atorvastatin	18 Years -	UNC Lineberger Comprehensive Cancer Center
Cellular Immune Augmentation in Colon and Rectal Cancer	NCT00257322	Colon Cancer Rectal Cancer	GM-CSF	18 Years -	University of California, Irvine
Cellular Immune Augmentation in Colon and Rectal Cancer	NCT00257322	Colon Cancer Rectal Cancer	GM-CSF	18 Years -	University of California, Irvine
Cellular Immune Augmentation in Colon and Rectal Cancer	NCT00257322	Colon Cancer Rectal Cancer	GM-CSF	18 Years -	University of California, Irvine

Spots Global Cancer Trial Database for metastatic rectal cancer