Short Course Radiation Therapy and Combination Chemotherapy for the Treatment of Stage II-III Rectal Cancer

Organ Preservation for Patients With Locally Advanced Rectal Adenocarcinoma: Evaluating the Efficacy of Short Course Radiation Therapy Followed by FOLFOX or CapeOX

This phase I trial investigates how well short-course radiation therapy followed by combination chemotherapy works in treating patients with stage II-III rectal cancer. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Chemotherapy drugs, such as leucovorin, fluorouracil, oxaliplatin, and capecitabine, 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. Giving short-course radiation therapy and combination chemotherapy may reduce the need for surgery and therefore improve quality of life.

Study Overview

• Status: Recruiting
• Conditions: Stage III Rectal Cancer AJCC v8; Stage IIIA Rectal Cancer AJCC v8; Stage IIIB Rectal Cancer AJCC v8; Stage IIIC Rectal Cancer AJCC v8; Rectal Adenocarcinoma; Stage IIA Rectal Cancer AJCC v8; Stage IIB Rectal Cancer AJCC v8; Stage II Rectal Cancer AJCC v8; Stage IIC Rectal Cancer AJCC v8; Locally Advanced Rectal Carcinoma
• Intervention / Treatment: Other: Quality-of-Life Assessment; Radiation: Intensity-Modulated Radiation Therapy; Drug: Fluorouracil; Drug: Leucovorin; Drug: Oxaliplatin; Procedure: Total Mesorectal Excision; Drug: Capecitabine; Behavioral: Surveillance

Detailed Description

PRIMARY OBJECTIVE:

I. Complete clinical response (cCR) rate of patients with clinical T3 and/or node-positive M0 rectal cancer being treated with short-course radiation therapy (SCRT) followed by 16 weeks of modified leucovorin, fluorouracil, and oxaliplatin (mFOLFOX)/capecitabine and oxaliplatin (CapeOX).

SECONDARY OBJECTIVES:

I. 1-year local recurrence free survival and 1-year progression free survival of the entire cohort, the cohort that initially undergoes non-operative management (NOM), and the cohort that initially undergoes total mesorectal excision (TME).

II. Physician-reported acute and late >= grade 3 toxicity rates. III. 1-year post-treatment patient health-related quality of life and anorectal function as per Patient Reported Outcomes Measurement and Information System (PROMIS).

IV. Explore how Signatera's residual disease test correlates with patient's cCR rates, local recurrence, progression-free, and overall survival rates.

V. Explore radiomics features from longitudinal diffusion weighted magnetic resonance imaging (MRI) (diffusion weighted imaging [DWI]) data and build a predictive model for treatment effect (complete response) in rectal cancer patients undergoing SCRT.

OUTLINE:

Patients undergo SCRT in the form of intensity-modulated radiation therapy (IMRT) over 5 fractions daily for 5 consecutive days. Beginning 11-18 days after the last day of radiation therapy, patients receive either oxaliplatin intravenously (IV) and leucovorin IV on day 1 and fluorouracil IV on days 1-3 (mFOLFOX6) or oxaliplatin IV on day 1 and capecitabine orally (PO) twice daily (BID) on days 1-14 (CapeOX). Treatment with mFOLFOX6 repeats every 2 weeks for up to 8 cycles, and treatment with CapeOX repeats every 3 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity. At 8-12 weeks after completion of all therapy, patients with residual tumor undergo TME. Patients with cCR undergo NOM.

After completion of study treatment, patients who underwent NOM are followed up every 3 months for 2 years, then every 6 months for 3 years. TME patients are followed up every 3-6 months for 2 years, then every 6 months for 3 years.

• Study Type: Interventional
• Enrollment (Estimated): 25
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Vincent Basehart; Phone Number: 310 267-8954; Email: vbasehart@mednet.ucla.edu

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • Recruiting
      • UCLA / Jonsson Comprehensive Cancer Center
      • Contact: Ann Raldow; Phone Number: 310-825-9771; Email: araldow@mednet.ucla.edu
      • Principal Investigator: Ann Raldow

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically confirmed rectal adenocarcinoma
• Patients must have stage II (cT3, cN0) or stage III (cT1-3, cN1-3) tumor as staged by MRI
• No evidence of metastatic disease
• Resectable primary lesion
• Karnofsky performance status (KPS) >= 70 or Eastern Cooperative Oncology Group (ECOG) 0-2
• Absolute neutrophil count (ANC) > 1.5 cell/mm^3
• Hemoglobin (Hgb) > 8.0 gm/dL
• Platelets (PLT) > 150,000/mm^3
• Total bilirubin < or equal to 1.5 x upper limit of normal
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < or equal to three times upper limit of normal
• If a woman is of childbearing potential, a negative serum pregnancy test must be documented prior to initiation of radiation therapy

Exclusion Criteria:

• Active treatment of a separate malignancy
• Distant metastatic disease as assessed by staging positron emission tomography (PET)/computed tomography (CT) or CT of the chest and abdomen within 6 weeks of starting radiation therapy
• Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
• Pregnant and/or breastfeeding
• Medical/psychological contraindication to MRI

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (IMRT, mFOLFOX6, CapeOX, TME); Patients undergo SCRT in the form of IMRT over 5 fractions daily for 5 consecutive days. Beginning 11-18 days after the last day of radiation therapy, patients receive either oxaliplatin IV and leucovorin IV on day 1 and fluorouracil IV on days 1-3 (mFOLFOX6) or oxaliplatin IV on day 1 and capecitabine PO BID on days 1-14 (CapeOX). Treatment with mFOLFOX6 repeats every 2 weeks for up to 8 cycles, and treatment with CapeOX repeats every 3 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity. At 8-12 weeks after completion of all therapy, patients with residual tumor undergo TME. Patients with cCR undergo NOM.

Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Radiation: Intensity-Modulated Radiation Therapy; Undergo IMRT; Other Names: IMRT; Intensity Modulated RT; Intensity-Modulated Radiotherapy; Radiation, Intensity-Modulated Radiotherapy; Drug: Fluorouracil; Given IV; Other Names: 5-Fluracil; Fluracil; 5 Fluorouracil; 5 Fluorouracilum; 5 FU; 5-Fluoro-2,4(1H, 3H)-pyrimidinedione; 5-Fluorouracil; 5-Fu; 5FU; AccuSite; Carac; Fluoro Uracil; Fluouracil; Flurablastin; Fluracedyl; Fluril; Fluroblastin; Ribofluor; Ro 2-9757; Ro-2-9757; Drug: Leucovorin; Given IV; Other Names: Folinic acid; Drug: Oxaliplatin; Given IV; Other Names: 1-OHP; Dacotin; Dacplat; Eloxatin; Ai Heng; Aiheng; Diaminocyclohexane Oxalatoplatinum; Eloxatine; JM-83; Oxalatoplatin; Oxalatoplatinum; RP 54780; RP-54780; SR-96669; Procedure: Total Mesorectal Excision; Undergo TME; Other Names: TME; Drug: Capecitabine; Given IV; Other Names: Xeloda; Ro 09-1978/000; Behavioral: Surveillance; Undergo NOM; Other Names: Epidemiology / Surveillance

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete clinical response rate	Kaplan-Meier analysis will be carried out and used to estimate for the entire cohort as well the non-operational management (NOM) and total mesorectal excision (TME) cohorts separately.	Up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Local recurrence-free survival	Kaplan-Meier analysis will be carried out and used to estimate for the entire cohort as well the NOM and TME cohorts separately.	At 1 year
Progression-free survival	Kaplan-Meier analysis will be carried out and used to estimate for the entire cohort as well the NOM and TME cohorts separately.	At 1 year
Incidence of adverse events	Physician-reported acute and late >= grade 3 toxicity rates for the entire cohort will be graded according to Common Terminology Criteria for Adverse Events version 5.0.	Up to 5 years
Health-related quality of life	Will be assessed by Patient Reported Outcomes Measurement and Information System and calculated and presented as a composite score. These scores will be calculated for the entire cohort as well as the NOM and TME cohorts separately.	At 1 year
Anorectal function	Will be assessed by Patient Reported Outcomes Measurement and Information System and calculated and presented as a composite score. These scores will be calculated for the entire cohort as well as the NOM and TME cohorts separately.	At 1 year
Signatera's residual disease test	Cox proportional hazards regression analysis will be used to assess the association of circulating tumor deoxyribonucleic acid with clinical response rates, local recurrent, progression-free, and overall survival rates.	Up to 5 years
Prediction of complete clinical response rate status by radiomics	The relationship between complete clinical response as a binary variable and longitudinal radiomics features from a sequence of four diffusion weighted imaging data points will be assessed via a logistic regression model with a random effect term to account for within-subject correlation.	Up to 5 years

Collaborators and Investigators

• Sponsor: Jonsson Comprehensive Cancer Center
• Collaborators: Natera, Inc.; The Joseph Drown Foundation
• Investigators: Principal Investigator: Ann Raldow, UCLA / Jonsson Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): February 11, 2021
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 15, 2027

Study Registration Dates

• First Submitted: January 7, 2021
• First Submitted That Met QC Criteria: January 7, 2021
• First Posted (Actual): January 11, 2021

Study Record Updates

• Last Update Posted (Actual): March 30, 2026
• Last Update Submitted That Met QC Criteria: March 25, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Rectal Diseases; Rectal Neoplasms; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Therapeutics; Nucleic Acids, Nucleotides, and Nucleosides; Enzymes and Coenzymes; Coordination Complexes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Nucleosides; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Uracil; Pyrimidinones; Coenzymes; Radiotherapy; Deoxyribonucleosides; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Capecitabine; Oxaliplatin; Fluorouracil; Leucovorin; Radiotherapy, Intensity-Modulated; dehydroftorafur
• Other Study ID Numbers: 20-001156 (Other Identifier: UCLA / Jonsson Comprehensive Cancer Center); NCI-2020-06479 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No