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Trial record 94 of 159 for:    colon cancer AND Capecitabine AND Fluorouracil

Prospectively Randomized Control Clinical Trial of FOLFOXIRI Preoperative Chemotherapy Alone on Rectal Cancer in Local Advance Comparing to Oral Capecitabine Combined With Long-term Radiation

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ClinicalTrials.gov Identifier: NCT03671252
Recruitment Status : Recruiting
First Posted : September 14, 2018
Last Update Posted : January 23, 2019
Sponsor:
Information provided by (Responsible Party):
Ruihua Xu, Sun Yat-sen University

Brief Summary:
Preoperative radiation and chemotherapy is the standard treatment for local advanced rectal cancer. The addition of oxaliplatin to capecitabine combined with radiotherapy does not improve local control and long-term survival. Most importantly,chemoradiotherapy significantly increased surgical complication and poor long-term quality of life .In the absence of effective measures of predicting chemo-sensitivity, there is considerable risk of using any two-drug regimen for neoadjuvant therapy. Simultaneous use of the three chemotherapeutic drugs may be able to reduce the likelihood of resistance to both dual drug regimen and single drug regimen. The purpose of this study is to compare the efficacy and safety of three chemotherapeutic regimen known as FOLFOXIRI (the drug 5-fluorouracil, oxaliplatin, Irinotecan) with standard radiotherapy combined with capecitabine in neoadjuvant therapy for local advanced rectal cancer. The drugs in the FOLFOXIRI regimen are all FDA(Food and Drug Administration) approved and have been used routinely to treat patients with advanced colorectal cancer.

Condition or disease Intervention/treatment Phase
Rectal Cancer Drug: FOLFOXIRI Drug: XELOX Other: Chemoradiotherapy Procedure: TME operation Procedure: efficacy evaluation Phase 3

Detailed Description:

Outline: This is a multicenter,prospectively,randomized control ,phase III clinical study.Patients are stratified according to the distance from the tumor to the anal margin(≤5cm,>5cm) and randomized to 1 of 2 treatment regimen.Patients will receive full supportive care while on this study.

Objectives:

Primary: To compare neoadjuvant chemotherpay of FOLFOXIRI with conventional capecitabine single-agent radiotherapy in local advanced rectal cancer with respect to 3-year disease free survival rate (DFS) .

Secondary:

  1. To compare postoperative 3-year local recurrence rate, 3-year distance metastasis free survival rate, 3-year overall survival between neoadjuvant FOLFOXIRI with capecitabine single-agent radiotherapy groups.
  2. To compare R0 Resection rate and surgical complication between the two groups.
  3. To evaluate the tumor regression grade(TRG) between the two groups.
  4. To evaluate the adverse event profile and Long term quality of life between the two groups.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 776 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Prospectively Randomized Control Clinical Trial of FOLFOXIRI Preoperative Chemotherapy Alone on Rectal Cancer in Local Advance Comparing to Oral Capecitabine Combined With Long-term Radiation
Actual Study Start Date : November 16, 2018
Estimated Primary Completion Date : September 25, 2025
Estimated Study Completion Date : September 25, 2028

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Experimental: Group 1
Patient will receive FOLFOXIRI regimen every two weeks for 4-6 cycles within 2-3 months.Two weeks after completing 3 and 6 cycles of FOLFOXIRI regimen,patients will have two efficacy evaluations according to RECIST criteria and toxicity evaluation .If the tumor is defined as no progression without severe toxicity at the first efficacy evaluation, the rest of 3 cycles of FOLFOXIRI regimen will be performed.If it is defined as progression of primary tumor or it is defined as progression of primary tumor and MRF(+)at the second efficacy evaluation,patients are assigned into active comparator group. If distant metastasis occurred during chemotherapy, patients are treated according to the guidelines for metastatic colorectal cancer.Chemotherapy is initiated at 3-4 weeks after R0 resection. XELOX regimen is performed post-operatively (about 4-6 cycles). If postoperative pathology confirmed as positive margin, postoperative chemoradiotherapy was given.
Drug: FOLFOXIRI
Irinotecan165 mg/m2、Oxaliplatin85 mg/m2、Left-calcium leucovorin 200mg/㎡,Intravenous infusion,first day. Then, 5-FU 1600 mg/m2/d×2 continuous intravenous infusion(total 3200 mg/m2,infusion 46 hours)in the next two days. Repeat every 14 days.

Drug: XELOX
XELOX consisting of 130 mg/m2 oxaliplatin administered intravenously on day 1 and 1,000 mg/m2 capecitabine administered orally twice daily on days 1-14 for a 3-week cycle.

Other: Chemoradiotherapy

Chemotherapy: oral capecitabine(1650 mg/m2)twice daily during radiotherapy without weekend breaks.

Radiation: Radiation therapy is administered via intensity-modulated radiation therapy (IMRT) with a linear accelerator, 6MV-X ray. The patients are scheduled to receive a GTV expanding 6mm to form PTV1 and CTV expanding 6mm to form PTV2. The dose of PTV1 is 50Gy/25 times for 35 days and the dose of PTV2 is 45Gy/25 times for 35 days. Patients were treated in consecutive days per week for a total of 5 weeks.


Procedure: TME operation
TME operation

Procedure: efficacy evaluation
chest/ abdominal CT、pelvic nuclear magnetic resonanceimaging、transrectal ultrasonography

Active Comparator: Active Comparator:Group 2
The patients are scheduled to receive chemoradiotherapy. After 5 weeks from the end of chemoradiotherapy, patients will have a efficacy evaluation according to RECIST criteria. If the tumor is defined as CR、PR or SD, and the TME operation is conducted within 5-10 weeks after chemoradiotherapy completion. If tumor is defined as progressive disease with the possibility of R0 resection, the operation was also conducted within 5-10 weeks after chemoradiotherapy . If tumor is defined as progressive disease without possibility of R0 resection, the palliative chemotherapy was performed . If distant metastasis occurred during chemoradiotherapy, patients are treated according to the guidelines for metastatic colorectal cancer. Adjuvant chemotherapy of XELOX is performed post-operatively (about 4-6 cycles).
Drug: XELOX
XELOX consisting of 130 mg/m2 oxaliplatin administered intravenously on day 1 and 1,000 mg/m2 capecitabine administered orally twice daily on days 1-14 for a 3-week cycle.

Other: Chemoradiotherapy

Chemotherapy: oral capecitabine(1650 mg/m2)twice daily during radiotherapy without weekend breaks.

Radiation: Radiation therapy is administered via intensity-modulated radiation therapy (IMRT) with a linear accelerator, 6MV-X ray. The patients are scheduled to receive a GTV expanding 6mm to form PTV1 and CTV expanding 6mm to form PTV2. The dose of PTV1 is 50Gy/25 times for 35 days and the dose of PTV2 is 45Gy/25 times for 35 days. Patients were treated in consecutive days per week for a total of 5 weeks.


Procedure: TME operation
TME operation

Procedure: efficacy evaluation
chest/ abdominal CT、pelvic nuclear magnetic resonanceimaging、transrectal ultrasonography




Primary Outcome Measures :
  1. 3-year disease free survival rate [ Time Frame: up to 5 years ]
    3-year disease free survival was defined as the interval from randomization to disease local recurrence and distance metastasis, death, or the last follow-up within 3 years. Patients without any event (metastasis or death) at the last follow-up date were regarded as random censoring.


Secondary Outcome Measures :
  1. 3-year local recurrence rate [ Time Frame: up to 5 years ]
    3-year disease local recurrence was defined as the interval from randomization to local recurrence, death, or the last follow-up within 3 years. Patients without any event (local recurrence or death) at the last follow-up date were regarded as random censoring.

  2. 3-year distance metastasis free survival rate [ Time Frame: up to 5 years ]
    3-year distance metastasis was defined as the interval from randomization to distance metastasis, death, or the last follow-up within 3 years. Patients without any event (distance metastasis or death) at the last follow-up date were regarded as random censoring.

  3. 5-year overall survival rate [ Time Frame: up to 5 years ]
    5-year overall survival was defined as the interval from the date of randomization until death of any cause or the last follow-up within 5 years.

  4. R0 Resection rate [ Time Frame: up to 5 years ]
    Percentage of included patients who were performed radical tumor resection among total included patients

  5. Surgical complication [ Time Frame: up to 5 years ]
    Surgical complication including anastomotic leakage , anastomotic stricture , intestinal obstruction , postoperative pelvic bleeding, and poor wound healing.

  6. Tumor regression grade (TRG) [ Time Frame: up to 5 years ]
    The tumor regression grade(TRG) were assessed using the Mandard TRG system.

  7. Number of Adverse events [ Time Frame: up to 5 years ]
    Treatment related adverse events were evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (CTCAE4.0)

  8. Long term quality of life [ Time Frame: up to 5 years ]
    Long term quality of life were assessed by European organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ C30)



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 1)Age: 18 to 75 years old;
  • 2)Histological diagnosis of rectal adenocarcinoma;
  • 3)Distance form anal margin ≤ 5cm: cT3-4aN + M0, there is no distant metastasis, lymph node positive, or the tumor breaking through the muscular layer, no invasion of the adjacent organs , positive MRF, it is estimated that R0 resection can be performed;
  • 4)From the anal margin>5cm: cT3c-4aN+M0, there is no distant metastasis, lymph node positive, or the tumor breaking through the muscular layer with invading the mesorectum more than 5mm, no invasion of the adjacent organs, positive MRF, it is estimated that R0 resection can be performed;
  • 5)Preoperative staging method: All patients undergoing anal examination, high-resolution MRI and/or EUS for preoperative staging. The diameter of parenteral lymph node ≥10mm, lymph node shape or the MRI characteristics is consistent with typical lymph node metastasis. If combined with EUS, the material should be submitted to the central assessment team for judgment when there is a contradiction in the staging method. Preoperative chest and abdomen CT, pelvic MRI are used for excluding distant metastasis;
  • 6)Confirmed as the lower edge of tumor is located within 12 cm from the anal margin by MRI examination
  • 7)There is no signs of intestinal obstruction, or obstruction of intestinal after treating with proximal colostomy has been relieved;
  • 8)Patients did not previously receive rectal surgery, chemotherapy or radiation therapy , biological treatment , except for endocrine therapy;
  • 9)ECOG Performance Status :0-1
  • 10)Life expectancy: more than 2 years;
  • 11)Laboratory values:Hematology: white blood cell count>4000/mm3; Platelet count>100000/mm3; Hemoglobin >10g/dL; Liver function: SGOT and SGPT < 1.5 upper limit of normal(ULN); Bilirubin< 1.5mg/dL; Renal function :Creatinine <1.8mg/dL.

Exclusion Criteria:

  • 1)Tumor invasion of surrounding tissue organs (T4b) by preoperative staging assessment;
  • 2)Obturator lymph node metastasis;
  • 3)Arrhythmia requires treatment with antiarrhythmia (except for beta-blockers or digoxin), symptomatic coronary artery disease, myocardial ischemia (myocardial infarction within the last 6 months) or congestive heart failure exceeding NYHA class II;
  • 4)Severe hypertension with poor control;
  • 5)History of HIV infection or active phase of chronic hepatitis B or C infection with high copy viral DNA;
  • 6)Other active serious infections according to NCI-CTC version 4.0;
  • 7)There is preoperative evidence for distant metastasis outside pelvis;
  • 8)Cachexia and organ function decompensation
  • 9)History of pelvic or abdominal radiotherapy;
  • 10)Multiple primary cancer;
  • 11)Patients with epilepcy requiring treatment ( steroids or antiepileptic treatment);
  • 12)History of other malignant tumors within 5 years, except for cured cervical carcinoma in situ or skin basal cell carcinoma;
  • 13)Drug abuse and medical, psychological or social conditions interfering patient participation in research or the evaluation of research results;
  • 14)Any allergy to clinical research drugs or any drugs associated with this study;
  • 15)Any unstable condition or condition that may endanger safety and compliance of patients;
  • 16)Pregnancy or the lactating female without adequate contraception.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03671252


Contacts
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Contact: ZhiZhong Pan 8613719388166 panzhzh@sysucc.org.cn
Contact: Rui-hua Xu 8613922206676 ruihxu@163.com

Locations
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China, Guangdong
Cancer center of Sun Yat-sen University Recruiting
Guangzhou, Guangdong, China, 510060
Contact: Rui-Hua Xu, MD, PhD    86-020-87343333    ruihxu@163.com   
Principal Investigator: Rui-hua Xu, MD, PhD         
Medical Oncology,Sun Yat-sen University Cancer Center Not yet recruiting
Guangzhou, Guangdong, China, 510060
Contact: Ruihua Xu, M.D,Ph.D    8613922206676    ruihxu@163.com   
Contact: Zhizhong Pan    8613719388166    panzhzh@sysucc.org.cn   
Sponsors and Collaborators
Sun Yat-sen University
Investigators
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Principal Investigator: Rui-hua Xu Sun Yat-sen University

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Responsible Party: Ruihua Xu, president of SunYat-sen University Cancer Center, Sun Yat-sen University
ClinicalTrials.gov Identifier: NCT03671252     History of Changes
Other Study ID Numbers: FAVORE Trial
First Posted: September 14, 2018    Key Record Dates
Last Update Posted: January 23, 2019
Last Verified: January 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Capecitabine
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents