Short Course Radiation Therapy and Combination Chemotherapy for the Treatment of Stage II-III Rectal Cancer
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| ClinicalTrials.gov Identifier: NCT04703101 |
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Recruitment Status :
Recruiting
First Posted : January 11, 2021
Last Update Posted : January 23, 2023
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Locally Advanced Rectal Carcinoma Rectal Adenocarcinoma 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 | Drug: Capecitabine Drug: Fluorouracil Radiation: Intensity-Modulated Radiation Therapy Drug: Leucovorin Drug: Oxaliplatin Other: Quality-of-Life Assessment Behavioral: Surveillance Procedure: Total Mesorectal Excision | Phase 1 |
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 (Clinical Trial) |
| Estimated Enrollment : | 25 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Masking Description: | Analysts blinded to patient outcome and sample order |
| Primary Purpose: | Treatment |
| Official Title: | Organ Preservation for Patients With Locally Advanced Rectal Adenocarcinoma: Evaluating the Efficacy of Short Course Radiation Therapy Followed by FOLFOX or CapeOX |
| Actual Study Start Date : | February 11, 2021 |
| Estimated Primary Completion Date : | October 15, 2025 |
| Estimated Study Completion Date : | October 15, 2026 |
| Arm | Intervention/treatment |
|---|---|
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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.
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Drug: Capecitabine
Given IV
Other Names:
Drug: Fluorouracil Given IV
Other Names:
Radiation: Intensity-Modulated Radiation Therapy Undergo IMRT
Other Names:
Drug: Leucovorin Given IV
Other Name: Folinic acid Drug: Oxaliplatin Given IV
Other Names:
Other: Quality-of-Life Assessment Ancillary studies
Other Name: Quality of Life Assessment Behavioral: Surveillance Undergo NOM
Other Name: Epidemiology / Surveillance Procedure: Total Mesorectal Excision Undergo TME
Other Name: TME |
- Complete clinical response rate [ Time Frame: Up to 5 years ]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.
- Local recurrence-free survival [ Time Frame: At 1 year ]Kaplan-Meier analysis will be carried out and used to estimate for the entire cohort as well the NOM and TME cohorts separately.
- Progression-free survival [ Time Frame: At 1 year ]Kaplan-Meier analysis will be carried out and used to estimate for the entire cohort as well the NOM and TME cohorts separately.
- Incidence of adverse events [ Time Frame: Up to 5 years ]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.
- Health-related quality of life [ Time Frame: At 1 year ]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.
- Anorectal function [ Time Frame: At 1 year ]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.
- Signatera's residual disease test [ Time Frame: Up to 5 years ]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.
- Prediction of complete clinical response rate status by radiomics [ Time Frame: Up to 5 years ]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.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04703101
| Contact: Vincent Basehart | 310 267-8954 | vbasehart@mednet.ucla.edu |
| United States, California | |
| UCLA / Jonsson Comprehensive Cancer Center | Recruiting |
| Los Angeles, California, United States, 90095 | |
| Contact: Ann Raldow 310-825-9771 araldow@mednet.ucla.edu | |
| Principal Investigator: Ann Raldow | |
| Principal Investigator: | Ann Raldow | UCLA / Jonsson Comprehensive Cancer Center |
| Responsible Party: | Jonsson Comprehensive Cancer Center |
| ClinicalTrials.gov Identifier: | NCT04703101 |
| Other Study ID Numbers: |
20-001156 NCI-2020-06479 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) 20-001156 ( Other Identifier: UCLA / Jonsson Comprehensive Cancer Center ) |
| First Posted: | January 11, 2021 Key Record Dates |
| Last Update Posted: | January 23, 2023 |
| Last Verified: | January 2023 |
| 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 |
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Adenocarcinoma Rectal Neoplasms Carcinoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Colorectal Neoplasms Intestinal Neoplasms Gastrointestinal Neoplasms Digestive System Neoplasms Neoplasms by Site Digestive System Diseases Gastrointestinal Diseases Intestinal Diseases Rectal Diseases |
Leucovorin Fluorouracil Capecitabine Oxaliplatin Antimetabolites Molecular Mechanisms of Pharmacological Action Antimetabolites, Antineoplastic Antineoplastic Agents Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antidotes Protective Agents Vitamin B Complex Vitamins |