Protocol Summary

Protocol No.: OCR12323

Sponsor Protocol No.: N1048

Study Title
A Phase II/III Trial of Neoadjuvant FOLFOX With Selective Use of Combined Modality Chemoradiation Versus Preoperative Combined Modality Chemoradiation for Locally Advanced Rectal Cancer Patients Undergoing Low Anterior Resection With Total Mesorectal Excision (PROSPECT)

Principal Investigator(s)
George, Thomas

The standard treatment for locally advanced rectal cancer involves chemotherapy and radiation, known as 5FUCMT, (the chemotherapy drugs 5-fluorouracil/capecitabine and radiation therapy) prior to surgery. Although radiation therapy to the pelvis has been a standard and important part of treatment for rectal cancer and has been shown to decrease the risk of the cancer coming back in the same area in the pelvis, some patients experience undesirable side effects from the radiation and there have been important advances in chemotherapy, surgery, and radiation which may be of benefit. The purpose of this study is to compare the effects, both good and bad, of the standard treatment of chemotherapy and radiation to chemotherapy using a combination regimen known as FOLFOX, (the drugs 5-fluorouracil (5-FU), oxaliplatin and leucovorin) and selective use of the standard treatment, depending on response to the FOLFOX. The drugs in the FOLFOX regimen are all FDA (Food and Drug Administration) approved and have been used routinely to treat patients with advanced colorectal cancer.

Phase III component: To compare neoadjuvant FOLFOX followed by Selective use of 5FUCMT (Group 1) to standard 5FUCMT (Group 2) with respect to the proportion of patients who achieve a pathologic complete response (pCR) at the time of surgical resection.

This research study is being done to see if radiation can be avoided for a select group of rectal cancer patients who have a good response to 6 treatments with a chemotherapy combination regimen known as FOLFOX. The proposed study does not use new agents or procedures, but rather sequences existing well established treatment strategies in a different way.

This is a multicenter, phase II/III study. Patients are stratified according to ECOG performance status (0 or 1 vs 2) and randomized to 1 of 2 treatment regimens. Patients will receive full supportive care while on this study.

Phase: Phase I/II (Cancer Control)

Age Group: Adult

Scope: National

Patients will receive FOLFOX chemotherapy once every two weeks for 6 cycles total over a period of 12 weeks. After completing FOLFOX chemotherapy, the patient will have an MRI scan or endorectal ultrasound (ERUS) to examine the tumor. If the tumor has not decreased in size by at least 20%, the patient will receive 5FUCMT (radiation with chemotherapy). If the tumor has decreased in size by 20%, then the patient will proceed directly to surgery.

Patients receive 5FUCMT including chemotherapy and radiation therapy for 5.5 weeks. Patients will be given either 5-fluorouracil or capecitabine and radiation therapy. After the chemoradiation therapy is completed, patients will proceed directly to surgery. Post-surgery, patients will receive FOLFOX chemotherapy once every two weeks for 8 cycles total over a period of 16 weeks. Patient observation with follow up evaluations and event monitoring will occur up to 8 years post randomization.

Detailed Eligibility
1. Ages 18 years-old and older
2. Diagnosis of rectal adenocarcinoma
3. Radiologically measurable or clinically evaluable disease as defined in the protocol
4. ECOG Performance Status (PS): 0, 1 or 2
5. For this patient, the standard treatment recommendation in the absence of a clinical trial would be combined modality neoadjuvant chemoradiation followed by curative intent surgical resection
6. Candidate for sphincter-sparing surgical resection prior to neoadjuvant therapy according to the primary surgeon
7. Primary surgeon is credentialed or is willing to be credentialed in Total Mesorectal Excision (TME), which entails submission of photos of a single TME specimen either before enrolling the first patient or by using the surgeon's 1st accrued case.
8. Clinical Stage: T2N1, T3N0, T3N1.
- N2 disease is to be estimated as four or more lymph nodes that are >= 10 mm.
- Clinical staging should be estimated based on the combination of the following assessments: physical exam by the primary surgeon, CT or PET/CT scan of the chest/abdomen/pelvis and either a pelvic MRI or an ultrasound (ERUS). If a pelvic MRI is peformed, it is acceptable to perform CT of the chest/abdomen, ommitting CT imaging of the pelvis.
9. The following laboratory values obtained = - Absolute neutrophil count (ANC) >= 1500/mm^3
- Platelet count >= 100,000/mm^3
- Hemoglobin > 8.0 g/dL
- Total bilirubin = - SGOT (AST) = - SGPT (ALT) = - Creatinine = - Negative pregnancy test done =10. Patient of child-bearing potential is willing to employ adequate contraception
11. Provide informed written consent
12. Willing to return to enrolling medical site for all study assessments

1. Clinical T4 tumors
2. Primary surgeon indicates need for abdominoperineal (APR) at baseline
3. Evidence that the tumor is adherent to or invading the mesorectal fascia on imaging studies such that the surgeon would not be able to perform an R0 resection (one with negative margins)
4. Tumor is causing symptomatic bowel obstruction (patients who have had a temporary diverting ostomy are eligible).
5. Chemotherapy within 5 years prior to registration. Hormonal therapy is allowable if the disease free interval is >= 5 years.
6. Any prior pelvic radiation
7. Other invasive malignancy =8. Any of the following because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects.
- Pregnant women
- Nursing women
* Men or women of childbearing potential who are unwilling to employ adequate contraception

Co-morbid illnesses or other concurrent disease which, in the judgment of the clinician obtaining informed consent, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.

Applicable Disease Sites
Colon Cancer
Gastrointestinal Cancer

Participating Institutions
UF Gainesville : Elena Nelson

Elena Nelson
Phone: +1 352-265-0680 ext. 50144


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