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

Primary Purpose

Locally Advanced Rectal Carcinoma, Rectal Adenocarcinoma, Stage II Rectal Cancer AJCC v8

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Capecitabine
Fluorouracil
Intensity-Modulated Radiation Therapy
Leucovorin
Oxaliplatin
Quality-of-Life Assessment
Surveillance
Total Mesorectal Excision
Sponsored by
Jonsson Comprehensive Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Locally Advanced Rectal Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • UCLA / Jonsson Comprehensive Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (IMRT, mFOLFOX6, CapeOX, TME)

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.
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.
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.
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.

Full Information

First Posted
January 7, 2021
Last Updated
January 19, 2023
Sponsor
Jonsson Comprehensive Cancer Center
Collaborators
The Joseph Drown Foundation, Natera, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT04703101
Brief Title
Short Course Radiation Therapy and Combination Chemotherapy for the Treatment of Stage II-III Rectal Cancer
Official Title
Organ Preservation for Patients With Locally Advanced Rectal Adenocarcinoma: Evaluating the Efficacy of Short Course Radiation Therapy Followed by FOLFOX or CapeOX
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 11, 2021 (Actual)
Primary Completion Date
October 15, 2025 (Anticipated)
Study Completion Date
October 15, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Jonsson Comprehensive Cancer Center
Collaborators
The Joseph Drown Foundation, Natera, Inc.

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Masking Description
Analysts blinded to patient outcome and sample order
Allocation
N/A
Enrollment
25 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment (IMRT, mFOLFOX6, CapeOX, TME)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Capecitabine
Other Intervention Name(s)
Ro 09-1978/000, Xeloda
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Fluorouracil
Other Intervention Name(s)
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
Intervention Description
Given IV
Intervention Type
Radiation
Intervention Name(s)
Intensity-Modulated Radiation Therapy
Other Intervention Name(s)
IMRT, Intensity Modulated RT, Intensity-Modulated Radiotherapy, Radiation, Intensity-Modulated Radiotherapy
Intervention Description
Undergo IMRT
Intervention Type
Drug
Intervention Name(s)
Leucovorin
Other Intervention Name(s)
Folinic acid
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Oxaliplatin
Other Intervention Name(s)
1-OHP, Ai Heng, Aiheng, Dacotin, Dacplat, Diaminocyclohexane Oxalatoplatinum, Eloxatin, Eloxatine, JM-83, Oxalatoplatin, Oxalatoplatinum, RP 54780, RP-54780, SR-96669
Intervention Description
Given IV
Intervention Type
Other
Intervention Name(s)
Quality-of-Life Assessment
Other Intervention Name(s)
Quality of Life Assessment
Intervention Description
Ancillary studies
Intervention Type
Behavioral
Intervention Name(s)
Surveillance
Other Intervention Name(s)
Epidemiology / Surveillance
Intervention Description
Undergo NOM
Intervention Type
Procedure
Intervention Name(s)
Total Mesorectal Excision
Other Intervention Name(s)
TME
Intervention Description
Undergo TME
Primary Outcome Measure Information:
Title
Complete clinical response rate
Description
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.
Time Frame
Up to 5 years
Secondary Outcome Measure Information:
Title
Local recurrence-free survival
Description
Kaplan-Meier analysis will be carried out and used to estimate for the entire cohort as well the NOM and TME cohorts separately.
Time Frame
At 1 year
Title
Progression-free survival
Description
Kaplan-Meier analysis will be carried out and used to estimate for the entire cohort as well the NOM and TME cohorts separately.
Time Frame
At 1 year
Title
Incidence of adverse events
Description
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.
Time Frame
Up to 5 years
Title
Health-related quality of life
Description
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.
Time Frame
At 1 year
Title
Anorectal function
Description
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.
Time Frame
At 1 year
Title
Signatera's residual disease test
Description
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.
Time Frame
Up to 5 years
Title
Prediction of complete clinical response rate status by radiomics
Description
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.
Time Frame
Up to 5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Vincent Basehart
Phone
310 267-8954
Email
vbasehart@mednet.ucla.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ann Raldow
Organizational Affiliation
UCLA / Jonsson Comprehensive Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
UCLA / Jonsson Comprehensive Cancer Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ann Raldow
Phone
310-825-9771
Email
araldow@mednet.ucla.edu
First Name & Middle Initial & Last Name & Degree
Ann Raldow

12. IPD Sharing Statement

Learn more about this trial

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

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