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

NCT ID: NCT04703101

Last Updated: 2025-11-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

25 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-02-11

Study Completion Date

2027-10-15

Brief Summary

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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

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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.

Conditions

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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

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Analysts blinded to patient outcome and sample order

Study Groups

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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.

Group Type EXPERIMENTAL

Capecitabine

Intervention Type DRUG

Given IV

Fluorouracil

Intervention Type DRUG

Given IV

Intensity-Modulated Radiation Therapy

Intervention Type RADIATION

Undergo IMRT

Leucovorin

Intervention Type DRUG

Given IV

Oxaliplatin

Intervention Type DRUG

Given IV

Quality-of-Life Assessment

Intervention Type OTHER

Ancillary studies

Surveillance

Intervention Type BEHAVIORAL

Undergo NOM

Total Mesorectal Excision

Intervention Type PROCEDURE

Undergo TME

Interventions

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Capecitabine

Given IV

Intervention Type DRUG

Fluorouracil

Given IV

Intervention Type DRUG

Intensity-Modulated Radiation Therapy

Undergo IMRT

Intervention Type RADIATION

Leucovorin

Given IV

Intervention Type DRUG

Oxaliplatin

Given IV

Intervention Type DRUG

Quality-of-Life Assessment

Ancillary studies

Intervention Type OTHER

Surveillance

Undergo NOM

Intervention Type BEHAVIORAL

Total Mesorectal Excision

Undergo TME

Intervention Type PROCEDURE

Other Intervention Names

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Ro 09-1978/000 Xeloda 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 IMRT Intensity Modulated RT Intensity-Modulated Radiotherapy Radiation, Intensity-Modulated Radiotherapy Folinic acid 1-OHP Ai Heng Aiheng Dacotin Dacplat Diaminocyclohexane Oxalatoplatinum Eloxatin Eloxatine JM-83 Oxalatoplatin Oxalatoplatinum RP 54780 RP-54780 SR-96669 Quality of Life Assessment Epidemiology / Surveillance TME

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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The Joseph Drown Foundation

UNKNOWN

Sponsor Role collaborator

Natera, Inc.

INDUSTRY

Sponsor Role collaborator

Jonsson Comprehensive Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Ann Raldow

Role: PRINCIPAL_INVESTIGATOR

UCLA / Jonsson Comprehensive Cancer Center

Locations

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UCLA / Jonsson Comprehensive Cancer Center

Los Angeles, California, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Vincent Basehart

Role: CONTACT

Phone: 310 267-8954

Email: [email protected]

Facility Contacts

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Ann Raldow

Role: primary

Other Identifiers

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NCI-2020-06479

Identifier Type: REGISTRY

Identifier Source: secondary_id

20-001156

Identifier Type: OTHER

Identifier Source: secondary_id

20-001156

Identifier Type: -

Identifier Source: org_study_id