Neoadjuvant FOLFOX6 Chemotherapy With or Without Radiation in Rectal Cancer (FOWARC)

This study is currently recruiting participants.
Verified November 2013 by Sun Yat-sen University
Sponsor:
Information provided by (Responsible Party):
Yanhong Deng, Sun Yat-sen University
ClinicalTrials.gov Identifier:
NCT01211210
First received: September 28, 2010
Last updated: November 14, 2013
Last verified: November 2013
  Purpose

RATIONALE: Preoperative 5-Fu based chemoradiation has become standard treatment for stage 2/3 rectal cancer. However whether these patients, especially T3N0-1M0 patients, really need radiation for local control after total mesentery excision being applied in routine practice is still unknown. And whether new drugs adding in can achieve better local and distant control is worth investigating.

PURPOSE: This randomized phase II trial is studying 5Fu based radiation therapy or FOLFOX based radiation or FOLFOX alone, comparing them to see how well they work when given before surgery in treating patients with intermediate risk resectable rectal cancer. It is not yet known whether 5-Fu based or FOLFOX based radiation therapy or even FOLFOX alone is more effective in treating rectal cancer.


Condition Intervention Phase
Rectal Cancer
Drug: fluorouracil
Drug: fluorouracil, oxaliplatin
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II/III Randomized Controlled Study of Neoadjuvant FOLFOX6 Treatment With or Without Radiation Compared to 5-Fu Based Chemoradiation in Treating Patients With Resectable Rectal Cancer

Resource links provided by NLM:


Further study details as provided by Sun Yat-sen University:

Primary Outcome Measures:
  • 3-year disease free survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Compare 3-year disease free survival in patients with resectable rectal cancer treated with either 5-Fu or FOLFOX based chemoradiotherapy or FOLFOX alone without radiation.


Secondary Outcome Measures:
  • objective response rate,pathologic complete response rate, sphincter-saving surgery rate, biomarkers, quality of life, toxic profile, convenience [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
    • Compare the rate of pathologic complete response and objective response rate in patients treated with these regimens.
    • Determine the increase in the number of patients who are able to undergo sphincter-saving surgery after treatment with these regimens.
    • Compare preoperative quality of life (QOL) of patients.
    • Determine the impact of oxaliplatin on neurotoxicity in patients treated with these regimens.
    • Compare the toxic effects of these regimens in these patients.
    • Compare the convenience of care in patients treated with these regimens.


Estimated Enrollment: 495
Study Start Date: June 2010
Estimated Study Completion Date: June 2020
Estimated Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: A: 5Fu with Radiation
Patients receive fluorouracil IV continuously and undergo radiotherapy once daily 5 days a week for 5-6 weeks.
Drug: fluorouracil
Drug: fluorouracil Given IV continuously Radiation: radiation therapy Given 5 days a week for 5-6 weeks
Other Names:
  • 5-Fu
  • RT
Experimental: B: FOLFOX with radiation
Patients receive FOLFOX for 5 cycles and undergo radiotherapy as in arm I from the second cycle of FOLFOX
Drug: fluorouracil, oxaliplatin
Drug: fluorouracil Given IV continuously Drug: oxaliplatin Given IV Radiation: radiation therapy Given 5 days a week for 5-6 weeks
Other Names:
  • 5-Fu
  • Oxaliplatin
  • RT
Experimental: C: FOLFOX alone
Patients receive FOLFOX for 4 cycles
Drug: fluorouracil, oxaliplatin
Drug: fluorouracil Given IV continuously Drug: oxaliplatin Given IV
Other Names:
  • 5-Fu
  • Oxaliplatin

Detailed Description:

OBJECTIVES:

Primary Compare the objective response rate and the rate of local-regional relapse in patients with resectable rectal cancer treated with either 5-Fu or FOLFOX based chemoradiotherapy or FOLFOX alone without radiation.

Secondary

  1. Compare the rate of pathologic complete response in patients treated with these regimens.
  2. Compare the local recurrence rate

2.Determine the increase in the number of patients who are able to undergo sphincter-saving surgery after treatment with these regimens.

3.Correlate genetic patterns and the presence or absence of specific tissue biomarkers with response and prognosis in patients treated with these regimens.

4.Compare preoperative quality of life (QOL) of patients treated with oral capecitabine versus continuous infusion with fluorouracil. pelvic auto-nerve function 5.Determine the impact of oxaliplatin on neurotoxicity in patients treated with these regimens.

6.Compare the toxic effects of these regimens in these patients. 7.Compare the convenience of care in patients treated with these regimens. 8.Determine the impact of the type of surgical management on QOL at 1 year postoperatively in these patients.

OUTLINE: This is a randomized, multi-center study. Patients are stratified according to participating center, gender, clinical tumor stage (stage II vs. stage III), and surgical intent (sphincter saving vs. non-sphincter saving). Patients are randomized to 1 of 4 treatment arms.

  • Arm A: Patients receive fluorouracil IV continuously and undergo radiotherapy once daily 5 days a week for 5-6 weeks.
  • Arm B: Patients receive FOLFOX for 4 cycles and undergo radiotherapy as in arm I from the second cycle of FOLFOX.
  • Arm C: Patients receive FOLFOX for 4 cycles Within 4-6 weeks after the completion of chemo radiotherapy, patients with responding or stable disease undergo surgery. Patients with progressive disease are treated at the discretion of the investigator and continue to be followed. Patients with progressive disease in arm III should received radiation.

Quality of life is assessed at baseline, at completion of chemo radiotherapy, and at 1 year after surgery.

After completion of study treatment, patients are followed every 3 months for 2 years, and then every 6 months for 3years.

PROJECTED ACCRUAL: A total of 495 patients will be accrued for this study within 5 years.

Eligibility Ages Eligible for Study: 18-75 Years old Genders Eligible for Study: Both Accepts Healthy Volunteers: No

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Diagnosis of adenocarcinoma of the rectum
  2. Age: 18-75 years old
  3. Stage of the primary tumor may be determined by ultrasound or MRI
  4. Stage II (T_3-4, N_0 [N_0 is defined as all imaged lymph nodes < 1.0 cm]) OR stage III (T_1-4, N_1-2 [with the definition of a clinically positive lymph node being any node ≥ 1.0 cm]
  5. Tumor palpable by digital rectal exam OR accessible by proctoscope or sigmoidoscope
  6. Distal border of the tumor must be located < 12 cm from the anal verge
  7. Tumor amenable to curative resection
  8. 15 days prior recruit, meet the following criteria: Hematopoietic

    • Absolute neutrophil count ≥ 1,200/mm^3
    • Platelet count ≥ 100,000/mm^3 Hepatic
    • Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
    • Alkaline phosphatase ≤ 2 times ULN
    • AST ≤ 2 times ULN*
    • No hepatic disease that would preclude study treatment or follow-up
    • No uncontrolled coagulopathy Renal
    • Creatinine clearance > 50 mL/min
    • No renal disease that would preclude study treatment or follow-up
  9. ECOG status: 0~1

Exclusion Criteria:

  1. Hypersensitivity to fluorouracil, or oxaliplatin
  2. No More than 4 weeks since prior participation in any investigational drug study
  3. More than 4 weeks since prior participation in any investigational drug study
  4. Clear indication of involvement of the pelvic side walls by imaging
  5. With distant metastasis
  6. History of invasive rectal malignancy, regardless of disease-free interval
  7. Fertile patients must use effective contraception
  8. Uncontrolled hypertension
  9. Cardiovascular disease that would preclude study treatment or follow-up
  10. Lack of upper gastrointestinal tract integrity or malabsorption syndrome,active upper gastrointestinal tract bleeding
  11. Synchronous colon cancer
  12. Pregnant or nursing, Fertile patients do not use effective contraception
  13. Other malignancy within the past 5 years except effectively treated squamous cell or basal cell skin cancer, melanoma in situ, carcinoma in situ of the cervix, or carcinoma in situ of the colon or rectum
  14. No psychiatric or addictive disorders, or other conditions that, in the opinion of the investigator, would preclude study participation
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01211210

Locations
China, Guangdong
Gastrointestinal Hospital, Sun Yatsen University Recruiting
Guangzhou, Guangdong, China, 510655
Contact: Yanhong Deng, MD    0086-020-38250745    dengyanh@mail.sysu.edu.cn   
Contact: Jianping Wang, MD    0086-020-38254020    13925106525@163.com   
Principal Investigator: Jianping Wang, MD         
Sponsors and Collaborators
Sun Yat-sen University
Investigators
Study Director: Jianping Wang, MD Sun Yatsen University
  More Information

No publications provided

Responsible Party: Yanhong Deng, Doctor, Sun Yat-sen University
ClinicalTrials.gov Identifier: NCT01211210     History of Changes
Other Study ID Numbers: GIHSYSU01
Study First Received: September 28, 2010
Last Updated: November 14, 2013
Health Authority: China: Food and Drug Administration

Keywords provided by Sun Yat-sen University:
rectal cancer
neoadjuvant therapy
oxaliplatin
radiation

Additional relevant MeSH terms:
Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Fluorouracil
Oxaliplatin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 16, 2014