Neoadjuvant FOLFOX6 Chemotherapy With or Without Radiation in Rectal Cancer

NCT01211210 | Unknown Phase 2 DMC

• 1 other identifier: GIHSYSU01
• Study Type: interventional
• Target: 495
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Rectal Cancer

Keywords

rectal cancer; neoadjuvant therapy; oxaliplatin; radiation

Outcome Measures

Primary Outcomes (1)

• 3-year disease free survival

  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.

  2 years

Secondary Outcomes (7)

• pathologic complete response rate

  1 years

• local recurrence rate

  3 years

• overall survival

  5 years

• sphincter-saving surgery rate

  1 year

• R0 resection rate

  1 year

Study Arms (3)

A: 5Fu with Radiation

ACTIVE COMPARATOR

Patients receive fluorouracil IV continuously and undergo radiotherapy once daily 5 days a week for 5-6 weeks.

Drug: fluorouracil

B: FOLFOX with radiation

EXPERIMENTAL

Patients receive FOLFOX for 5 cycles and undergo radiotherapy as in arm I from the second cycle of FOLFOX

Drug: fluorouracil, oxaliplatin

C: FOLFOX alone

EXPERIMENTAL

Patients receive FOLFOX for 4 cycles

Drug: fluorouracil, oxaliplatin

Interventions

fluorouracil DRUG

Drug: fluorouracil Given IV continuously Radiation: radiation therapy Given 5 days a week for 5-6 weeks

Also known as: 5-Fu, RT

A: 5Fu with Radiation

fluorouracil, oxaliplatin DRUG

Drug: fluorouracil Given IV continuously Drug: oxaliplatin Given IV Radiation: radiation therapy Given 5 days a week for 5-6 weeks

Also known as: 5-Fu, Oxaliplatin, RT

B: FOLFOX with radiation

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of adenocarcinoma of the rectum
• Age: 18-75 years old
• Stage of the primary tumor may be determined by ultrasound or MRI
• 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 \[with the definition of a clinically positive lymph node being any node ≥ 1.0 cm\]
• Tumor palpable by digital rectal exam OR accessible by proctoscope or sigmoidoscope
• Distal border of the tumor must be located \< 12 cm from the anal verge
• Tumor amenable to curative resection
• 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

You may not qualify if:

• Hypersensitivity to fluorouracil, or oxaliplatin
• No More than 4 weeks since prior participation in any investigational drug study
• More than 4 weeks since prior participation in any investigational drug study
• Clear indication of involvement of the pelvic side walls by imaging
• With distant metastasis
• History of invasive rectal malignancy, regardless of disease-free interval
• Fertile patients must use effective contraception
• Uncontrolled hypertension
• Cardiovascular disease that would preclude study treatment or follow-up
• Lack of upper gastrointestinal tract integrity or malabsorption syndrome，active upper gastrointestinal tract bleeding
• Synchronous colon cancer
• Pregnant or nursing, Fertile patients do not use effective contraception
• 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
• No psychiatric or addictive disorders, or other conditions that, in the opinion of the investigator, would preclude study participation

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Gastrointestinal Hospital, Sun Yatsen University

Guangzhou, Guangdong, 510655, China

Location

Related Publications (11)

• Zhang T, Shi L, Jian L, Jiang J, Qiu Y, Xie F, Zhang J, Peng H, Zhong L, Chen Y, Zhong Y, Deng Y; FOWARC Group. Clinical Benefit and Cost-Effectiveness of FOLFOX Versus LCCRT in Neoadjuvant Treatment for Patients with Locally Advanced Rectal Cancer: An Economic Analysis of the FOWARC and PROSPECT Trial. Ann Surg Oncol. 2025 Dec 11. doi: 10.1245/s10434-025-18802-8. Online ahead of print.

  PMID: 41379261 DERIVED

• Wan H, Weng J, Cai J, Chen Z, Li P, Han J, Li Z, Wan Z, Yuan Z, Gan Y, Huang M, Li X, Li T, Liu X, Wang X, Yu H, Liu B, Lin J, Luo Y. Nodal Downstaging in Patients With Rectal Cancer: Survival Is Promising if YpN0 Is Achieved. Dis Colon Rectum. 2025 Oct 1;68(10):1162-1171. doi: 10.1097/DCR.0000000000003846. Epub 2025 Jul 8.

  PMID: 40626521 DERIVED

• Shi L, Zhang J, Deng Y. Associations of pretreatment emotional distress with adherence to therapy for patients with locally advanced rectal cancer: a post hoc analysis of the Chinese FOWARC phase 3 randomized clinical trial. BMC Med. 2025 May 21;23(1):293. doi: 10.1186/s12916-025-04128-5.

  PMID: 40399932 DERIVED

• Zhang J, Chi P, Shi L, Cui L, Gao J, Li W, Wei H, Cheng L, Huang Z, Cai G, Zhao R, Huang Z, Zhou H, Wei Y, Zhang H, Zheng J, Huang Y, Cai Y, Zhou Z, Kang L, Huang M, Wu X, Peng J, Ren D, Lan P, Wang J, Deng Y. Neoadjuvant Modified Infusional Fluorouracil, Leucovorin, and Oxaliplatin With or Without Radiation Versus Fluorouracil Plus Radiation for Locally Advanced Rectal Cancer: Updated Results of the FOWARC Study After a Median Follow-Up of 10 Years. J Clin Oncol. 2025 Feb 20;43(6):633-640. doi: 10.1200/JCO-24-01676. Epub 2024 Dec 13.

  PMID: 39671537 DERIVED

• Li L, Xu B, Zhuang Z, Li J, Hu Y, Yang H, Wang X, Lin J, Zhou R, Chen W, Ran D, Huang M, Wang D, Luo Y, Yu H. Accurate tumor segmentation and treatment outcome prediction with DeepTOP. Radiother Oncol. 2023 Jun;183:109550. doi: 10.1016/j.radonc.2023.109550. Epub 2023 Feb 21.

  PMID: 36813177 DERIVED

• Xie Y, Lin J, Wang X, Wang P, Zhuang Z, Zou Q, Cai D, Huang Z, Bai L, Tang G, Huang M, Wang J, Yu H, Luo Y. The Addition of Preoperative Radiation Is Insufficient for Lateral Pelvic Control in a Subgroup of Patients With Low Locally Advanced Rectal Cancer: A Post Hoc Study of a Randomized Controlled Trial. Dis Colon Rectum. 2021 Nov 1;64(11):1321-1330. doi: 10.1097/DCR.0000000000001935.

  PMID: 33990500 DERIVED

• Deng Y, Chi P, Lan P, Wang L, Chen W, Cui L, Chen D, Cao J, Wei H, Peng X, Huang Z, Cai G, Zhao R, Huang Z, Xu L, Zhou H, Wei Y, Zhang H, Zheng J, Huang Y, Zhou Z, Cai Y, Kang L, Huang M, Wu X, Peng J, Ren D, Wang J. Neoadjuvant Modified FOLFOX6 With or Without Radiation Versus Fluorouracil Plus Radiation for Locally Advanced Rectal Cancer: Final Results of the Chinese FOWARC Trial. J Clin Oncol. 2019 Dec 1;37(34):3223-3233. doi: 10.1200/JCO.18.02309. Epub 2019 Sep 26.

  PMID: 31557064 DERIVED

• Hu H, Huang J, Lan P, Wang L, Huang M, Wang J, Deng Y. CEA clearance pattern as a predictor of tumor response to neoadjuvant treatment in rectal cancer: a post-hoc analysis of FOWARC trial. BMC Cancer. 2018 Nov 20;18(1):1145. doi: 10.1186/s12885-018-4997-y.

  PMID: 30458734 DERIVED

• Qin Q, Ma T, Deng Y, Zheng J, Zhou Z, Wang H, Wang L, Wang J. Impact of Preoperative Radiotherapy on Anastomotic Leakage and Stenosis After Rectal Cancer Resection: Post Hoc Analysis of a Randomized Controlled Trial. Dis Colon Rectum. 2016 Oct;59(10):934-42. doi: 10.1097/DCR.0000000000000665.

  PMID: 27602924 DERIVED

• Deng Y, Chi P, Lan P, Wang L, Chen W, Cui L, Chen D, Cao J, Wei H, Peng X, Huang Z, Cai G, Zhao R, Huang Z, Xu L, Zhou H, Wei Y, Zhang H, Zheng J, Huang Y, Zhou Z, Cai Y, Kang L, Huang M, Peng J, Ren D, Wang J. Modified FOLFOX6 With or Without Radiation Versus Fluorouracil and Leucovorin With Radiation in Neoadjuvant Treatment of Locally Advanced Rectal Cancer: Initial Results of the Chinese FOWARC Multicenter, Open-Label, Randomized Three-Arm Phase III Trial. J Clin Oncol. 2016 Sep 20;34(27):3300-7. doi: 10.1200/JCO.2016.66.6198. Epub 2016 Aug 1.

  PMID: 27480145 DERIVED

• Huang M, Lin J, Yu X, Chen S, Kang L, Deng Y, Zheng J, Luo Y, Wang L, Lan P, Wang J. Erectile and urinary function in men with rectal cancer treated by neoadjuvant chemoradiotherapy and neoadjuvant chemotherapy alone: a randomized trial report. Int J Colorectal Dis. 2016 Jul;31(7):1349-57. doi: 10.1007/s00384-016-2605-7. Epub 2016 Jun 6.

  PMID: 27270480 DERIVED

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Fluorouracil; Oxaliplatin

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Coordination Complexes; Organic Chemicals

Study Officials

• Jianping Wang, MD

  Sun Yatsen University

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Doctor

Study Record Dates

• First Submitted: September 28, 2010
• First Posted: September 29, 2010
• Study Start: June 1, 2010
• Primary Completion: June 1, 2017
• Study Completion: June 1, 2020
• Last Updated: May 22, 2015

Record last verified: 2013-11

Locations

CN (1)