Clinical trial NCT04703101: 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
Overall status: RECRUITING
Phase: PHASE1
Conditions: 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
Lead sponsor: Jonsson Comprehensive Cancer Center
Sponsor class: OTHER
Collaborators: name: The Joseph Drown Foundation
name: Natera, Inc.
First posted: 2021-01-11
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Complete clinical response rate
timeFrame: Up to 5 years
Secondary outcomes:
measure: Local recurrence-free survival
timeFrame: At 1 year
measure: Progression-free survival
timeFrame: At 1 year
measure: Incidence of adverse events
timeFrame: Up to 5 years
measure: Health-related quality of life
timeFrame: At 1 year
measure: Anorectal function
timeFrame: At 1 year
measure: Signatera's residual disease test
timeFrame: Up to 5 years
measure: Prediction of complete clinical response rate status by radiomics
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA / Jonsson Comprehensive Cancer Center
state: California
Study officials:
affiliation: UCLA / Jonsson Comprehensive Cancer Center
name: Ann Raldow
role: PRINCIPAL_INVESTIGATOR
References: