Conditions: Rectal Cancer
Keywords: 5-FU cetuximab radiation adenocarcinoma of the rectum neoadjuvant therapy
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 13
Healthy volunteers: no

Brief summary:
The standard treatment for rectal cancer is to receive the chemotherapeutic drug 5-fluorouracil (5-FU) with radiation therapy before having surgery to remove the rectal cancer. This is known as neoadjuvant chemoradiotherapy. The purpose of this research study is to determine if Cetuximab improves the benefits of neoadjuvant chemoradiotherapy when given with 5-FU and radiation therapy.

Detailed description:
The epidermal growth factor receptor (EGFR) present in normal and tumor cells is involved in signaling pathways affecting cellular growth, differentiation, proliferation and programmed cell death. Overexpression of EGFR has been associated with poorer prognosis in colorectal cancer. Cetuximab targets and blocks EGFR and has been shown to be safe and effective in treating colorectal cancer and head and neck cancers.

The primary hypothesis is that cetuximab in combination with standard 5-FU and radiation as neoadjuvant therapy would improve pathological complete response (pCR) compared to the historical rate (30% versus 10%). The regimen would be considered promising if 5 or more of 25 evaluable participants achieve pCR. The probability of observing this outcome is 0.91 and 0.10 if the true pCR rate is 30% and 10%, respectively.

Arms:
arm 1: Cetuximab: Participants first receive cetuximab at the initial dose of 400 mg/m2 intravenously (IV) administered over 120 minutes, followed by weekly infusions at 250 mg/m2 over 60 minutes. Cetuximab is given as single agent during the first 3 weeks on study and then in combination with 5-FU and radiation.

Radiation: Radiation therapy given as standard of care is initiated after the 3rd dose of cetuximab with a total dose of 50.4 Gray (Gy) in 28 fractions over approximately 5.5 weeks.

5-FU: Participants receive 5-Fluorouracil (5-FU) continuous infusion through central venous access at 225 mg/m2/day given 7 days a week starting day 1 of radiation (no later than 3 days) and lasting the duration of radiation therapy.

Duration of neoadjuvant therapy is estimated to be 9 weeks. Surgery follows at week 13-17. Sigmoidoscopy is performed for biopsy prior to the 1st dose and after 3rd dose of cetuximab before the initiation of radiation and/or 5-FU.

Interventions: intervention 1: Cetuximab intervention 2: 5-Fluorouracil intervention 3: Radiation
Intervention descriptions: intervention 1: None intervention 2: None intervention 3: None

Protocol document: