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

Rectal Adenocarcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04703101
• Other study ID #: 20-001156
• Secondary ID: NCI-2020-0647920
• Status: Recruiting
• Phase: Phase 1
• Start date: February 11, 2021
• Est. completion date: October 15, 2026

Study information

• Verified date: January 2024
• Source: Jonsson Comprehensive Cancer Center
• Contact: Vincent Basehart
• Phone: 310 267-8954
• Email: vbasehart[@]mednet.ucla.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 25
• Est. completion date: October 15, 2026
• Est. primary completion date: October 15, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Adenocarcinoma
• Locally Advanced Rectal Carcinoma
• Rectal Adenocarcinoma
• Rectal Neoplasms
• Stage II Rectal Cancer AJCC v8
• Stage IIA Rectal Cancer AJCC v8
• Stage IIB Rectal Cancer AJCC v8
• Stage IIC Rectal Cancer AJCC v8
• Stage III Rectal Cancer AJCC v8
• Stage IIIA Rectal Cancer AJCC v8
• Stage IIIB Rectal Cancer AJCC v8
• Stage IIIC Rectal Cancer AJCC v8

Intervention

Drug:
• Capecitabine
Given IV
• Fluorouracil
Given IV

Radiation:
• Intensity-Modulated Radiation Therapy
Undergo IMRT

Drug:
• Leucovorin
Given IV
• Oxaliplatin
Given IV

Other:
• Quality-of-Life Assessment
Ancillary studies

Behavioral:
• Surveillance
Undergo NOM

Procedure:
• Total Mesorectal Excision
Undergo TME

Locations

Country	Name	City	State
United States	UCLA / Jonsson Comprehensive Cancer Center	Los Angeles	California

Sponsors (3)

Lead Sponsor	Collaborator
Jonsson Comprehensive Cancer Center	Natera, Inc., The Joseph Drown Foundation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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