Non-Operative Management and Early Response Assessment in Rectal Cancer (NOM-ERA)

The Washington University

Status: Active, not recruiting

Conditions: Adenocarcinoma of the Lower Rectum

Treatments: Radiation: Radiation therapy; Drug: CAPOX regimen; Drug: FOLFOX regimen

Study type: Interventional

Funder types: Other

Identifiers

NCT03904043

201904029

Details and patient eligibility

About

The investigators' data from a phase I study of short course radiation therapy followed by chemotherapy showed 74% complete clinical response (cCR). Given the promising response rate, the investigators are evaluating short course radiation therapy (SCRT) followed by chemotherapy in a multi-institution phase II trial to validate the cCR rate of this treatment paradigm. SCRT has not been prospectively evaluated in non-operative management for patients with non-metastatic rectal adenocarcinoma.

Enrollment: 63 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

• Diagnosis of biopsy proven stage I-IIIB (cT1-3, N0-2a, M0) adenocarcinoma of the rectum; staging must also be based on multidisciplinary evaluation including MRI

• Tumor ≤ 12 cm from anal verge as determined by MRI or endoscopy

• Clinically detectable (MR, endoscopy, or DRE) tumor present

• Eastern Cooperative Oncology Group (ECOG) performance status 0-2

• At least 18 years of age

• Adequate bone marrow function defined as:

  • Absolute neutrophil count (ANC) > 1,500 cells/mm3
  • Hemoglobin> 8 g/dl
  • Platelets >100,000 cells/mm3

• Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.

• Able to understand and willing to sign an Institutional Review Board (IRB)-approved written informed consent document.

Exclusion Criteria

• Prior radiation therapy, chemotherapy or extirpative surgery for rectal cancer.
• Prior oxaliplatin or capecitabine use for any malignancy
• No prior radiation therapy to the pelvis.
• A history of other malignancy (except non-melanomatous skin cancers) with the exception of malignancies for which all treatment was completed at least 2 years before registration and the patient has no evidence of disease.
• Currently receiving any investigational agents.
• A history of allergic reaction attributed to compounds of similar chemical or biologic composition to capecitabine, 5FU, oxaliplatin, or leucovorin.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia.
• Pregnant and/or breastfeeding. Women of childbearing potential must have a negative serum pregnancy test within 14 days of study entry.
• Patients with HIV are eligible unless their CD4+ T-cell counts are < 350 cells/mcL or they have a history of AIDS-defining opportunistic infection within the 12 months prior to registration. Concurrent treatment with effective antiretroviral therapy (ART) according to Department of Health and Human Services (DHHS) treatment guidelines is recommended. HIV testing for patients without a history of HIV is not a protocol requirement.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

63 participants in 2 patient groups

Radiation + FOLFOX

Experimental group

Description:

* Pelvic radiotherapy 5GY x 5 fractions once daily * Radiation to extra-mesorectal node 7 Gy x 5 fractions once daily * FOLFOX should begin 2-4 weeks after completion of radiotherapy and will consist of FOLFOX x 8 cycles (16 weeks). * Oxaliplatin day 1 every 14 days * Leucovorin day 1 every 14 days. Levoleucovorin may be substituted if leucovorin is not available. * 5-FU bolus day 1 every 14 days * 5-FU infusion day 1 every 14 days over 46 hours * An optional simultaneous integrated boost of 30 Gy in 5 fractions to the primary tumor is permitted

Treatment:

Drug: FOLFOX regimen

Radiation: Radiation therapy

Radiation + CAPOX

Experimental group

Description:

* Pelvic radiotherapy 5GY x 5 fractions once daily * Radiation to extra-mesorectal node 7 Gy x 5 fractions once daily * CAPOX should begin 2-4 weeks after completion of radiotherapy and will consist of CAPOX x 5 cycles (15 weeks). * Capecitabine 1000 mg/m\^2 by mouth twice per day on days 1-14 of every 21 day cycle * Oxaliplatin 130 mg/m\^2 intravenous on day 1 of each 21 day cycle * An optional simultaneous integrated boost of 30 Gy in 5 fractions to the primary tumor is permitted

Treatment:

Drug: CAPOX regimen

Radiation: Radiation therapy