Testing the Addition of an Anti-Cancer Drug, Irinotecan, to the Standard Chemotherapy Treatment (FOLFOX) after Long-Course Radiation Therapy for Advanced-Stage Rectal Cancers to Improve the Rate of Complete Response and Long-Term Rates of Organ Preservation and Continuing Response

Active:	Yes
Cancer Type:	Colon/Rectal Cancer Unknown Primary	NCT ID:	NCT05610163
Trial Phases:	Phase II Phase III	Protocol IDs:	A022104 (primary) A022104 NCI-2022-07800
Eligibility:	18 Years and older, Male and Female	Study Type:	Treatment
Study Sponsor:	Alliance for Clinical Trials in Oncology
NCI Full Details:	http://clinicaltrials.gov/show/NCT05610163

Summary

This phase II/III trial compares the effect of usual treatment approach alone (FOLFOX or CAPOX after chemoradiation) with using FOLFIRINOX after chemoradiation in patients with stage II-III rectal cancer. Combination chemotherapy regiments, such as FOLFIRINOX [folinic acid (leucovorin), fluorouracil, irinotecan, and oxaliplatin], FOLFOX (leucovorin, fluorouracil, and oxaliplatin), or CAPOX (capecitabin and oxaliplatin) use more than one anticancer drug that 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. FOLFOX or CAPOX are used after chemoradiation as usual treatment for rectal cancer. Giving FOLFIRINOX after chemoradiation may increase the response rate for the primary rectal tumor and lead to higher rates of clinical complete response (and thus a chance to avoid surgery) compared to FOLFOX or CAPOX after chemoradiation in patients with locally advanced rectal cancer.

Objectives

PRIMARY OBJECTIVES:
I. To evaluate and compare the clinical complete response (cCR) rates in patients with locally advanced rectal cancer treated with neoadjuvant long-course radiotherapy (LCRT) followed by neoadjuvant modified leucovorin fluorouracil, irinotecan, and oxaliplatin (mFOLFIRINOX) versus neoadjuvant LCRT followed by neoadjuvant modified leucovorin, fluorouracil, and oxaliplatin (mFOLFOX6). (Phase II)
II. To evaluate and compare disease-free survival (DFS) in patients with locally advanced rectal cancer treated with neoadjuvant LCRT followed by neoadjuvant mFOLFIRINOX versus neoadjuvant LCRT followed by neoadjuvant mFOLFOX6. (Phase III)

SECONDARY OBJECTIVES:
I. To evaluate and compare organ-preservation-time (OPT) between two treatment arms.
II. To evaluate and compare time to distant metastasis between two treatment arms.
III. To evaluate and compare overall survival (OS) between two treatment arms.
IV. To evaluate and compare toxicity profiles of total neoadjuvant therapy (TNT) between two treatment arms.

EXPLORATORY OBJECTIVE:
I. Evaluation of circulating tumor deoxyribonucleic acid (ctDNA) kinetics during neoadjuvant therapy & surveillance and to correlate with radiographic, pathologic, and clinical outcomes.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I:

LCRT: Patients undergo long course chemoradiation therapy for up to 5 weeks.

CONSOLIDATION: Patients receive either FOLFOX (consisting of leucovorin IV over 2 hours on day 1 of each cycle, fluorouracil IV bolus over 2-4 minutes and IV continuous infusion over 46-48 hours on day 1 of each cycle, and oxaliplatin IV over 2 hours on day 1 of each cycle) or CAPOX (consisting of capecitabine PO on days 1-14 of each cycle, and oxaliplatin IV over 2 hours on day 1 of each cycle). Treatment with FOLFOX repeats every 2 weeks for up to 8 cycles (16 weeks) in the absence of disease progression or unacceptable toxicity. Treatment with CAPOX repeats every 3 weeks for up to 5 cycles (15 weeks) in the absence of disease progression or unacceptable toxicity.

ARM II:

LCRT: Patients undergo long course chemoradiation therapy for up to 5 weeks.

CONSOLIDATION: Patients receive FOLFIRINOX (consisting of leucovorin IV over 2 hours on day 1 of each cycle, fluorouracil IV continuous infusion over 46-48 hours on day 1 of each cycle, oxaliplatin IV over 2 hours on day 1 of each cycle, and irinotecan IV over 30-90 minutes on day 1 of each cycle) Treatment with FOLFIRINOX repeats every 2 weeks for up to 8 cycles (16 weeks) in the absence of disease progression or unacceptable toxicity.

All patients undergo computed tomography (CT) scan, magnetic resonance imaging (MRI), collection of blood samples, and sigmoidoscopy throughout the trial and undergo biopsy during screening.

Patients are followed for up to five years after finishing study treatment.

Treatment Sites in Georgia

Emory Saint Joseph's Hospital
5665 Peachtree Dunwoody Road NE
Atlanta, GA 30342
www.emoryhealthcare.org

Emory University Hospital - Midtown
550 Peachtree Street NE
Atlanta, GA 30308
404-686-4411
www.emoryhealthcare.org

Winship Cancer Institute of Emory University
1365 Clifton Road NE
Building C
Atlanta, GA 30322
404-778-5180
winshipcancer.emory.edu

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