Organ Preservation Program Using Short-Course Radiation & FOLFOXIRI in Rectal Cancer

Rectal Cancer Clinical Trial

Official title:

Phase II Trial of Organ Preservation Program Using Short-Course Radiation and FOLFOXIRI for Rectal Cancer (SHORT-FOX)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04380337
• Other study ID #: IRB-56027
• Secondary ID: IRB-56027COR0019
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: May 21, 2020
• Est. completion date: January 17, 2026

Study information

• Verified date: March 2024
• Source: Stanford University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of the research is to evaluate whether both chemotherapy and radiotherapy can lead to higher rates of clinical complete response leading to organ preservation in human subjects with cancer. The objective is to learn if this treatment approach may safely be used as an alternative to the standard treatment for rectal cancer and to know the quality-of-life in these patients.

Description:

Primary Objective: To assess clinical complete response of an organ preservation approach using short course radiation followed by intensified chemotherapy.

Secondary Objective: To assess safety in all enrolled patients, local regrowth rate and other cancer specific outcomes (metastasis-free survival, colostomy-free survival and overall survival), longitudinal health-related quality of life of this organ preservation approach

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 38
• Est. completion date: January 17, 2026
• Est. primary completion date: January 17, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 1. Pathologically (histologically or cytologically) proven diagnosis of adenocarcinoma of rectum requiring total mesorectal excision as deemed by multidisciplinary evaluation

• 2.At least 18 years of age

• 3.For women of childbearing potential or who are not postmenopausal (see Appendix B for Definition of Menopausal Status), a negative urine or serum pregnancy test must be done. Also, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) for the duration of study participation and for up to 4 weeks following the study. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

• 4.ECOG 0, 1, or 2

• 5.Ability to understand and the willingness to personally sign the written IRB approved informed consent document.

• 6.Patients must have acceptable organ and marrow function as defined below:

• Absolute neutrophil count (ANC) >1,500/uL

• Hg > 8.0 g/dL; if blood transfusion is performed for achieving adequate hemoglobin level, the level should stay above goal for at least 1 week after transfusion

• Platelets >100,000/uL

• Total bilirubin <1.5X normal institutional limits

• aspartate aminotransferase (AST) (SGOT) / alanine aminotransferase (ALT)(SGPT) < 3X upper limit of normal

• Creatinine <1.5X upper limit of normal or creatinine clearance (CrCL)>50 by Cockcroft-Gault

• 7 Clinical stage >T2N0 or low T2N0 rectal cancer (AJCC, 8th ed.) including no metastases based on the following diagnostic workup:

• General history and physical examination with DRE (if deemed appropriate by treating physician) within 45 days prior to enrollment

• Sigmoidoscopy within 90 days prior to enrollment

The following imaging studies are required within 45 days prior to enrollment:

• CT chest/abdomen/pelvis

• MRI Pelvis

Exclusion Criteria:

• 1.Prior pelvic RT or chemotherapy for rectal cancer.

• 2.Upper T2N0 rectal cancers eligible for sphincter-preservation surgery

• 3.Use of other investigational agents.

• 4.Ongoing or active infections requiring systemic antibiotic treatment or uncontrolled intercurrent illness including but not limited to symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

• 5.Any concurrent malignancy other than non-melanoma skin cancer or carcinoma in situ of the cervix. Patients with any previous malignancy without evidence of disease for >3 years will be allowed to enter the trial.

• 6.Known hypersensitivity to 5-FU compounds.

• 7.Pregnant and breastfeeding women are excluded. Women of child-bearing potential who are unwilling or unable to use an acceptable method of birth control to avoid pregnancy for the entire study period and for up to 4 weeks after the study are excluded. (This applies to women who have experienced menarche and have not undergone successful surgical sterilization or are not postmenopausal).

Because patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy, known HIV-positive patients with detectable viral loads and/or receiving combination anti-retroviral therapy are excluded from the study.

• 8.Primary unresectable rectal cancer (tumor invading adjacent organs and en bloc resection will not achieve negative margins).

Related Conditions & MeSH terms

• Rectal Cancer
• Rectal Neoplasms

Intervention

Drug:
• FOLFOXIRI
Chemotherapy regimen of Oxaliplatin 85mg/m2 , Leucovorin 400 mg/m2 , Irinotecan 165mg/m2 , 5-Fluorouracil
• FOLFOX regimen
Chemotherapy regimen of Oxaliplatin 85mg/m2, Leucovorin 400 mg/m2, 5-Fluorouracil 2400mg/m2
• XELOX
Chemotherapy regimen of Oxaliplatin 130 mg/m2, Capecitabine 1000mg/m2

Radiation:
• IMRT
Radiotherapy (5 Gy x 5 fractions) with an additional boost fraction (5 Gy x 1 fraction) delivered sequentially

Locations

Country	Name	City	State
United States	Stanford University	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Stanford University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical complete response (cCR)	Proportion of patients who achieve a clinical complete response following therapy, expressed as a number and proportion without dispersion.	8 (+/-4 ) weeks
Secondary	Measure Toxicity	Toxicity defined as non-hematologic grade 4 adverse events using CTCAE v5 or higher toxicity at least possibly related to treatment, and assessed up to 3 months after completion of radiotherapy (RT) and chemotherapy, expressed as a number and proportion without dispersion"	3 months
Secondary	Local regrowth rate	Local regrowth is defined as the presence of adenocarcinoma within the rectal wall or within the mesorectum confirmed by pathology, expressed as a percentage with its 95% confidence interval.	2 year
Secondary	Disease free survival (DFS)	DFS defined as the time from the start date of RT to the date of the first documented progression or death due to any cause assessed up to 2 years after completion of chemotherapy. Patients will be censored at the last date of follow-up if lost to follow-up prior to two years, expressed as a median with interquartile range.	2 years
Secondary	Colostomy-free survival	Colostomy-free survival defined as the time from the start date of RT to the date of colostomy or death due to any cause assessed up to 2 years after completion of chemotherapy, expressed as a median with interquartile range. Patients will be censored at the last date of follow-up if lost to follow-up prior to two years.	2 years
Secondary	Overall Survival (OS)	OS defined as death from any cause from start date of RT until death, study completion, or loss to follow-up, whichever occurs first. This will be reported as median survival time with interquartile range.	84 months