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

Jonsson Comprehensive Cancer Center

Status and phase

Enrolling

Phase 1

Conditions

Stage IIC Rectal Cancer AJCC v8

Stage IIA Rectal Cancer AJCC v8

Locally Advanced Rectal Carcinoma

Rectal Adenocarcinoma

Stage II Rectal Cancer AJCC v8

Stage III Rectal Cancer AJCC v8

Stage IIB Rectal Cancer AJCC v8

Stage IIIC Rectal Cancer AJCC v8

Stage IIIB Rectal Cancer AJCC v8

Stage IIIA Rectal Cancer AJCC v8

Treatments

Behavioral: Surveillance

Other: Quality-of-Life Assessment

Radiation: Intensity-Modulated Radiation Therapy

Drug: Capecitabine

Drug: Oxaliplatin

Drug: Leucovorin

Drug: Fluorouracil

Procedure: Total Mesorectal Excision

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT04703101

20-001156 (Other Identifier)

NCI-2020-06479 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment

25 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No 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

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

25 participants in 1 patient group

Treatment (IMRT, mFOLFOX6, CapeOX, TME)

Experimental group

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.

Treatment: