Chemotherapy Alone or Chemotherapy Plus Radiation Therapy in Treating Patients With Locally Advanced Rectal Cancer Undergoing Surgery

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Alliance for Clinical Trials in Oncology
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:
NCT01515787
First received: January 18, 2012
Last updated: August 28, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
Colorectal Cancer
Drug: FOLFOX (chemotherapy)
Other: 5 FUCMT (chemoradiation)
Procedure: surgery
Procedure: magnetic resonance imaging or endorectal ultrasound
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official 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

Resource links provided by NLM:


Further study details as provided by Alliance for Clinical Trials in Oncology:

Primary Outcome Measures:
  • Pelvic R0 resection rate (Phase II) [ Time Frame: Up to 18 weeks ] [ Designated as safety issue: No ]
  • DFS (Phase III) [ Time Frame: Up to 8 years ] [ Designated as safety issue: No ]
  • Time to local recurrence (TLR) [ Time Frame: Up to 8 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Pathologic complete response [ Time Frame: Up to 18 weeks ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: Up to 8 years ] [ Designated as safety issue: No ]
  • Adverse event (AE) profiles [ Time Frame: Up to 8 years ] [ Designated as safety issue: Yes ]
  • Rates of receiving pre- or post-operative 5FUCMT [ Time Frame: Up to 30 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 1060
Study Start Date: January 2012
Estimated Primary Completion Date: July 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 1

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 shrunk in size by 20%, the patient will receive 5FUCMT (radiation with chemotherapy). If the tumor has decreased in size by at least 20%, then the patient will proceed directly to surgery.

If all borders of the tumor are normal post surgery, then the patient receives six additional cycles of FOLFOX chemotherapy. If all borders of the tumor are not normal then the patient receives chemoradiation therapy for 5.5 weeks after surgery. After chemoradiation, additional cycles of FOLFOX or similar chemotherapy will be recommended for 4 cycles or 8 weeks. Patient observation with follow up evaluations and event monitoring will occur up to 8 years post randomization.

Drug: FOLFOX (chemotherapy)
Oxaliplatin 85 mg/m^2 IV over 2 hours on day 1, leucovorin 400 mg/m^2 bolus IV over 2 hours on day 1 and 5-fluorouracil 400 mg/m^2 bolus over 5-15 minutes then 2400 mg/m^2 continual over 46-48 hours total dose IV on days 1-2. The treatment schedule repeats based on the group. Dose modifications are allowed based on adverse events.
Other: 5 FUCMT (chemoradiation)
5-fluorouracil 225 mg/m^2 per day continuous IV infusion administered concurrently with radiation therapy for 5 or 7 days per week OR capecitabine 825 mg/m^2 twice daily administered orally and concurrently with radiation therapy for 5 days per week. Dose modifications are allowed based on adverse events.
Procedure: surgery
low anterior resection with total mesorectal excision
Procedure: magnetic resonance imaging or endorectal ultrasound
Active Comparator: Group 2
Patients receive 5FUCMT 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. 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.
Drug: FOLFOX (chemotherapy)
Oxaliplatin 85 mg/m^2 IV over 2 hours on day 1, leucovorin 400 mg/m^2 bolus IV over 2 hours on day 1 and 5-fluorouracil 400 mg/m^2 bolus over 5-15 minutes then 2400 mg/m^2 continual over 46-48 hours total dose IV on days 1-2. The treatment schedule repeats based on the group. Dose modifications are allowed based on adverse events.
Other: 5 FUCMT (chemoradiation)
5-fluorouracil 225 mg/m^2 per day continuous IV infusion administered concurrently with radiation therapy for 5 or 7 days per week OR capecitabine 825 mg/m^2 twice daily administered orally and concurrently with radiation therapy for 5 days per week. Dose modifications are allowed based on adverse events.
Procedure: surgery
low anterior resection with total mesorectal excision

Detailed Description:

OUTLINE: 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.

OBJECTIVES:

Primary

  1. Phase II component: To assure that neoadjuvant FOLFOX followed by selective use of 5FUCMT group (Group 1) maintains the current high rate of pelvic R0 resection and is consistent with non-inferiority for time to local recurrence (TLR).
  2. Phase III component: To compare neoadjuvant FOLFOX followed by selective use of 5FUCMT (Group 1) to standard 5FUCMT (Group 2) with respect to the co-primary endpoints of the Time to Local Recurrence (TLR) and Disease-Free Survival (DFS).

Secondary

  1. To determine if the neoadjuvant FOLFOX followed by selective use of 5FUCMT (Group 1) is non-inferior to the standard group 5FUCMT (Group 2) with respect to the proportion of patients who achieve a pathologic complete response (pCR) at the time of surgical resection.
  2. To determine if the neoadjuvant FOLFOX followed by selective use of 5FUCMT (Group 1) is non-inferior to the standard 5FUCMT (Group 2) with respect to overall survival.
  3. To evaluate and compare the adverse event profile and surgery complications between two groups.
  4. To estimate the proportion of patients in the selective group (Group 1) who receive: 1) pre-operative 5FUCMT; 2) post-operative 5FUCMT; 3) either pre- or post-operative 5FUCMT.

Event monitoring of patients will continue up to 8 years post randomization.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Registration Inclusion Criteria:

  1. Age ≥ 18 years at diagnosis
  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. Clinical staging should be estimated based on the combination of the following assessments: physical exam by the primary surgeon, CT scan of the chest/abdomen/pelvis and either a pelvic MRI or an ultrasound (ERUS).

    Clinical stage N2 disease is to be estimated as four or more lymph nodes that are ≥ 10mm.

  9. Preoperative proctoscopy with distal end of tumor tissue evident between 5 and 12 cm from the anal verge, inclusive. Tumors should not extend below 5cm. Tumors may extend above 12 cm provided distal tumor is located between 5-12 cm.
  10. The following laboratory values obtained ≤ 28 days prior to registration:

    • Absolute neutrophil count (ANC) ≥ 1500/mm^3
    • Platelet count ≥ 100,000/mm^3
    • Hemoglobin > 8.0 g/dL
    • Total bilirubin ≤ 1.5 x upper limit of normal (ULN)
    • SGOT (AST) ≤ 3 x ULN
    • SGPT (ALT) ≤ 3 x ULN
    • Creatinine ≤1.5 x ULN
  11. Negative pregnancy test done ≤ 7 days prior to registration, for women of childbearing potential only.
  12. Patient of child-bearing potential is willing to employ adequate contraception.
  13. Provide informed written consent
  14. Willing to return to enrolling medical site for all study assessments

Registration Exclusion Criteria:

  1. Clinical T4 tumors
  2. Primary surgeon indicates need for abdominoperineal (APR) at baseline
  3. Evidence that tumor is adjacent to (defined as within 3 mm of) the mesorectal fascia on pre-operative MRI or ERUS/pelvic CT scan.
  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 ≤ 5 years prior to registration. Exceptions are colonic polyps, non-melanoma skin cancer or carcinoma in-situ of the cervix.
  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
  9. 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01515787

  Show 307 Study Locations
Sponsors and Collaborators
Alliance for Clinical Trials in Oncology
Investigators
Study Chair: Deborah Schrag, MD Dana-Farber Cancer Institute
  More Information

Additional Information:
No publications provided

Responsible Party: Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier: NCT01515787     History of Changes
Other Study ID Numbers: N1048, NCCTG-N1048, CDR0000715321, NCI-2012-00234, U10CA031946
Study First Received: January 18, 2012
Last Updated: August 28, 2014
Health Authority: United States: Food and Drug Administration
United States: NCI Central Institutional Review Board

Keywords provided by Alliance for Clinical Trials in Oncology:
stage IIA rectal cancer
stage IIIA rectal cancer
stage IIIB rectal cancer

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases

ClinicalTrials.gov processed this record on September 30, 2014