Non-Operative Radiation Management of Adenocarcinoma of the Lower Rectum (NORMAL-R)

The Washington University

Status and phase: Completed; Phase 2

Conditions: Cancer of Rectum; Cancer of the Rectum; Rectum Cancer; Adenocarcinoma of the Rectum; Neoplasm, Rectum; Rectum Neoplasms; Rectal Cancer

Treatments: Radiation: Radiation; Drug: Leucovorin; Drug: Fluorouracil; Drug: Oxaliplatin

Study type: Interventional

Funder types: Other

Identifiers

NCT02641691

201512140

Details and patient eligibility

About

The purpose of this research study is to look at how tumors responds to a short course of radiation (5 days) followed by 8 cycles of chemotherapy.

Enrollment: 20 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Diagnosis of biopsy proven stage I-IIIB (cT1-3, N0-1, M0) adenocarcinoma of the rectum; staging must also be based on multidisciplinary evaluation including MRI and/or endorectal ultrasound

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

• ECOG performance status 0-2

• At least 18 years of age

• Adequate bone marrow function defined as:

  • ANC > 1,500 cells/mm3
  • Hgb > 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 IRB-approved written informed consent document.

Exclusion criteria

• No clinically detectable (MR, endoscopy or DRE) tumor present
• Prior radiation therapy, chemotherapy or extirpative surgery for rectal cancer.
• Any evidence of disease from another malignancy or history of other malignancy ≤ 3 years previous with the exception of basal cell or squamous cell carcinoma of the skin which were treated with local resection only or carcinoma in situ of the cervix). Patients with history of prostate cancer treated without radiotherapy and no evidence of disease are eligible.
• Currently receiving any investigational agents.
• A history of allergic reaction attributed to compounds of similar chemical or biologic composition to 5FU, oxaliplatin, or leucovorin.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant and/or breastfeeding. Women of childbearing potential must have a negative serum pregnancy test within 14 days of study entry.
• Known HIV-positivity and on combination antiretroviral therapy because of the potential for pharmacokinetic interactions with the study drugs. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

20 participants in 1 patient group

Arm 1: Radiation/Oxaliplatin/Leucovorin/5-FU

Experimental group

Description:

* Radiotherapy will consist of five fractions, delivered once daily, to a total dose of 25Gy at 5 Gy per fraction. * An optional concomitant boost may be delivered to the primary tumor of 1-2 Gy per day (30-35 Gy to tumor total). If a boost is given then the maximum allowed dose to small bowel is 25 Gy. * Chemotherapy should begin two weeks (9-12 working days) after completion of radiotherapy. * Oxaliplatin will be given intravenous (IV) over 2 hours on Day 1 every 14 days for a maximum of 8 cycles. * Leucovorin will be given IV over 2 hours on Day 1 every 14 days for a maximum of 8 cycles. * 5-FU bolus will given IV push on Day 1 every 14 days for a maximum of 8 cycles. * 5-FU infusion will be given continuous IV on Day 1 over 46 hours every 14 days for a maximum of 8 cycles * Alternatively, capecitabine/oxaliplatin (CAPE PO 1000 mg/m2 BID days 1-14 Q21 days, oxaliplatin IV 130 mg/m2 IV Q21 days on day 1) x 5 cycles over 15 weeks may be administered instead of FOLFOX

Treatment:

Drug: Oxaliplatin

Drug: Fluorouracil

Drug: Leucovorin

Radiation: Radiation