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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04703101
Recruitment Status : Recruiting
First Posted : January 11, 2021
Last Update Posted : January 18, 2022
Sponsor:
Information provided by (Responsible Party):
Jonsson Comprehensive Cancer Center

Brief 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.

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

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.

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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
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.
Drug: Capecitabine
Given IV
Other Names:
  • Ro 09-1978/000
  • Xeloda

Drug: Fluorouracil
Given IV
Other Names:
  • 5 Fluorouracil
  • 5 Fluorouracilum
  • 5 FU
  • 5-Fluoro-2,4(1H, 3H)-pyrimidinedione
  • 5-Fluorouracil
  • 5-Fluracil
  • 5-Fu
  • 5FU
  • AccuSite
  • Carac
  • Fluoro Uracil
  • Fluouracil
  • Flurablastin
  • Fluracedyl
  • Fluracil
  • Fluril
  • Fluroblastin
  • Ribofluor
  • Ro 2-9757
  • Ro-2-9757

Radiation: Intensity-Modulated Radiation Therapy
Undergo IMRT
Other Names:
  • IMRT
  • Intensity Modulated RT
  • Intensity-Modulated Radiotherapy
  • Radiation, Intensity-Modulated Radiotherapy

Drug: Leucovorin
Given IV
Other Name: Folinic acid

Drug: Oxaliplatin
Given IV
Other Names:
  • 1-OHP
  • Ai Heng
  • Aiheng
  • Dacotin
  • Dacplat
  • Diaminocyclohexane Oxalatoplatinum
  • Eloxatin
  • Eloxatine
  • JM-83
  • Oxalatoplatin
  • Oxalatoplatinum
  • RP 54780
  • RP-54780
  • SR-96669

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




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

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


Contacts
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Contact: Vincent Basehart 310 267-8954 vbasehart@mednet.ucla.edu

Locations
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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         
Sponsors and Collaborators
Jonsson Comprehensive Cancer Center
Investigators
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Principal Investigator: Ann Raldow UCLA / Jonsson Comprehensive Cancer Center
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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 18, 2022
Last Verified: January 2022

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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
Additional relevant MeSH terms:
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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