Clinical trial NCT00462501
Conditions: Colorectal Cancer
Keywords: stage II rectal cancer stage III rectal cancer adenocarcinoma of the rectum
Sponsor: Memorial Sloan Kettering Cancer Center
Start date: 2007-03-01; Completion date: 2014-02-01
Enrollment: 35 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
RATIONALE: Drugs used in chemotherapy, such as oxaliplatin, fluorouracil, and leucovorin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of rectal cancer by blocking blood flow to the tumor. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving combination chemotherapy and bevacizumab together with radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

PURPOSE: This clinical trial is studying how well giving combination chemotherapy and bevacizumab with or without radiation therapy works in treating patients with locally advanced rectal cancer

Detailed description:
OBJECTIVES:

Primary

* Determine whether neoadjuvant chemotherapy comprising oxaliplatin, fluorouracil, leucovorin calcium (FOLFOX), and bevacizumab can be substituted for pelvic radiotherapy without compromising R0 resection rates in patients with locally advanced rectal cancer.

Secondary

* Determine whether a 3-year local recurrence rate of ≤ 10% can be achieved in patients treated with this regimen.
* Determine the proportion of patients who achieve a complete pathologic response after treatment with this regimen.

OUTLINE: This is a non-randomized, open-label, pilot study.

* Neoadjuvant chemotherapy: Patients receive oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and bevacizumab IV over 10 minutes on day 1 and fluorouracil IV continuously over 48 hours on days 1 and 2 in weeks 1, 3, 5, and 7. Patients then receive oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV continuously over 48 hours on days 1 and 2 in weeks 9 and 11. Treatment continues in the absence of disease progression or unacceptable toxicity.

Within 3 weeks after completion of neoadjuvant chemotherapy, patients undergo restaging evaluation. Patients with no evidence of disease progression by endorectal ultrasound (ERUS), pelvic MRI, and CT scan of the chest/abdomen AND who remain candidates for R0 resection may proceed directly to surgical resection within 4-6 weeks after completion of neoadjuvant chemotherapy. Patients with progressive disease who are not candidates for an R0 resection, proceed to neoadjuvant chemoradiotherapy.

* Neoadjuvant chemoradiotherapy: Patients undergo pelvic radiotherapy 5 days a week and receive concurrent fluorouracil IV continuously for 5½ weeks. Within 4-7 weeks after completion of chemoradiotherapy, patients undergo surgical resection.

After completion of study treatment, patients are followed every 3 months for 1 year and then every 6 months for 5 years.

PROJECTED ACCRUAL: A total of 36 patients will be accrued for this study.

Arms: arm 1: FOLFOX/Bevacizumab will be given for 4 cycles over 8 weeks; FOLFOLX6 without Bevacizumab will be given for an additional 2 cycles over 4 weeks. Oxaliplatin will be given on Day 1 of each cycle over 2 hours at 85 mg/m2 IV. Leucovorin will be given Day 1 of each cycle over 2 hours at 400 mg/m2 IV. Fluorouracil will be given on Day 1 of each cycle at 400 mg/m2 IVP, then Fluorouracil will be given at 1200 mg/m2 IVCI over Day 1 and 2. Bevacizumab will be given at 5mg/kg over 10 minutes on day 1. Patients will undergo re-staging within 3 weeks of completing their 6th cycle of FOLFOX. If the reassessment reveals that there has been no disease progression as compared to the pre-treatment evaluation and the patient remains a candidate for an R0 resection. If the surgical oncologist's reassessment is that the patient is not a candidate for an R0 resection, the patient will proceed to standard pre-operative radiation with synchronous infusional 5-fluorouracil.
Interventions: intervention 1: bevacizumab intervention 2: fluorouracil intervention 3: leucovorin calcium intervention 4: oxaliplatin intervention 5: conventional surgery intervention 6: radiation therapy
Intervention descriptions: intervention 1: None intervention 2: None intervention 3: None intervention 4: None intervention 5: None intervention 6: None

Protocol documents: