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Capecitabine, Oxaliplatin, and Radiation Therapy in Treating Patients With Stage II or Stage III Anal Cancer

Primary Purpose

Anal Cancer

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Capecitabine
Oxaliplatin
Radiation Therapy (XRT)
Sponsored by
M.D. Anderson Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Anal Cancer focused on measuring stage II anal cancer, stage IIIA anal cancer, stage IIIB anal cancer, squamous cell carcinoma of the anus, Capecitabine, Xeloda, Oxaliplatin, Eloxatin, Radiotherapy, XRT

Eligibility Criteria

16 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Previously untreated patients with histologically proven squamous cell carcinoma of the anal canal. American Joint Committee on Cancer (AJCC) stage II-IIIB (TX 1-4, NX, MO). Age >/= 16 yrs old. Eastern Cooperative Oncology Group (ECOG) Performance Scale (PS) 0-1. Adequate organ function including: Absolute neutrophil Count (ANC) >/= 1,500/uL, Platelets >/= 100,000/uL, Total bilirubin </= 1.5 * upper limit of normal (ULN), aspartate aminotransferase (AST or SGOT)/alanine aminotransferase (ALT or SGPT) </= 3 * ULN, Creatinine </= 1.5mg/dL or Creatinine Clearance (CrCL) >/= 50 cc/min. Patients may have measurable or non-measurable disease. Patients with measurable disease, as defined by the modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria, have at least one lesion that can be accurately measured in at least one dimension with longest diameter to be recorded >/= 20 mm using conventional techniques or >/= 10 mm with spiral CT scan (with minimum lesion size no less than double the slice thickness). Lesions seen on colonoscopy or barium studies are not considered measurable lesions. A negative pregnancy test in all women of child-bearing potential, within two weeks of initiating treatment. The effects of oxaliplatin and capecitabine on the developing human fetus at the recommended therapeutic dose are unknown. For this reason and because cytotoxic agents are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Ability to understand and the willingness to sign the written informed consent/authorization document. Exclusion Criteria: Prior chemotherapy with oxaliplatin, capecitabine, or 5-fluorouracil. Prior radiation to the pelvis. Prior surgery for anal cancer excluding prior biopsy. Known history of dihydropyrimidine (DPD) deficiency. Known history of hypersensitivity to platinum-containing compounds. Peripheral neuropathy of >/= grade 2 by Common Terminology Criteria for Adverse Events (CTCAE) 3.0. Calculated creatinine clearance (CrCl) < 50 cc/min. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit adherence with study requirements. Gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for intravenous (IV) alimentation. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with oxaliplatin or capecitabine, breast feeding should be discontinued. Because of the known interaction of capecitabine and coumadin, patients taking coumadin will be ineligible. Patients will be requested to discontinue coumadin and utilize Lovenox if agreeable. Patients must have discontinued coumadin for 7 days before initiating therapy. No prior malignancies (excluding non-melanomatous skin neoplasms) over the past 5 years. HIV-positive patients receiving combination anti-retroviral therapy are excluded from this study because of possible pharmacokinetic interactions with capecitabine or oxaliplatin. This exclusion is for patient safety since patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy, and because very few HIV-positive anal canal cancer patients are seen at this institution. This hinders us from accruing enough patients to adequately test the safety of this regimen in this population. Patients with symptomatic pulmonary fibrosis.

Sites / Locations

  • M. D. Anderson Cancer Center at University of Texas

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Capecitabine + Oxaliplatin + XRT

Arm Description

Capecitabine (825 mg/m^2 twice a day, Monday-Friday during weeks 1, 2, 4, and 5) and Oxaliplatin (50 mg/m^2, Days 1, 8, 22, 29) during the duration of radiation therapy only. Radiotherapy once daily on days 1-3, 6-10, 13-17, 20-24, 27-31, 34-38, and 41-42. Participants with T3-4 lesions undergo radiotherapy once daily on days 43 and 44. The final dose of radiation therapy determined by the T stage of the primary tumor. Radiotherapy = XRT.

Outcomes

Primary Outcome Measures

2 Year Failure Free Survival
Treatment failure defined as: Biopsy proven residual disease identified 12 -14 weeks after the conclusion of chemoradiation therapy, Treatment-related mortality or Disease recurrence.

Secondary Outcome Measures

Number of Participants With Complete Response at 2 Years
Response determined by computed tomography (CT)/magnetic resonance imaging (MRI), digital rectal examination, and proctoscopy, and a biopsy performed for clinical suspicion of residual or progressive disease. Response Evaluation Criteria in Solid Tumors (RECIST) where evaluation of target lesions Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): At least a 30% decrease in sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD; Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.
Number of Participants With 2-year Colostomy-Free Survival
Colostomy-free survival reported as number of participants who did not develop local recurrence or require salvage resection with colostomy.
2-year Local Regional Control
2-Year Median Overall Survival
Number of Participants With Progression-Free Survival at 2-Year

Full Information

First Posted
October 6, 2004
Last Updated
March 22, 2023
Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00093379
Brief Title
Capecitabine, Oxaliplatin, and Radiation Therapy in Treating Patients With Stage II or Stage III Anal Cancer
Official Title
A Phase II Study of Capecitabine (Xeloda)/Oxaliplatin (Eloxatin) With Concomitant Radiotherapy (XRT), XELOX/RT in Squamous Cell Carcinoma of the Anal Canal
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Completed
Study Start Date
April 2004 (undefined)
Primary Completion Date
July 2012 (Actual)
Study Completion Date
July 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
RATIONALE: Drugs used in chemotherapy, such as capecitabine and oxaliplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. Capecitabine may stop the growth of tumor cells by stopping blood flow to the tumor. Radiation therapy uses high-energy x-rays to damage tumor cells. Capecitabine and oxaliplatin may make tumor cells more sensitive to radiation therapy. Combining capecitabine and oxaliplatin with radiation therapy may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving capecitabine and oxaliplatin together with radiation therapy works in treating patients with stage II or stage III anal cancer.
Detailed Description
OBJECTIVES: Primary Determine time to treatment failure in patients with stage II-IIIB squamous cell carcinoma of the anal canal treated with capecitabine, oxaliplatin, and radiotherapy (i.e. Capecitabine (Xeloda)/Oxaliplatin (Eloxatin) With Concomitant Radiotherapy (XRT) shortened to XELOX/XRT). Determine the toxic effects of this regimen in these patients. Secondary Determine the complete response rate in patients treated with this regimen. Determine 2-year local regional control in patients treated with this regimen. Determine 2-year colostomy-free survival in patients treated with this regimen. Determine 2-year median overall survival in patients treated with this regimen. Determine 2-year progression-free survival in patients treated with this regimen. OUTLINE: Patients receive oral capecitabine* twice daily on days 1-2, 6-10, 20-24, 27-31, and 41-42, and undergo radiotherapy* once daily on days 1-3, 6-10, 13-17, 20-24, 27-31, 34-38, and 41-42. Patients also receive oxaliplatin intravenous (IV) over 2 hours on days 1, 8, 22, and 29. Treatment continues in the absence of disease progression or unacceptable toxicity. NOTE: *Patients with T3-4 lesions also receive oral capecitabine twice daily and undergo radiotherapy once daily on days 43 and 44. Patients are followed at 4-6 and 12 weeks and then periodically thereafter. PROJECTED ACCRUAL: A total of 71 patients will be accrued for this study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Anal Cancer
Keywords
stage II anal cancer, stage IIIA anal cancer, stage IIIB anal cancer, squamous cell carcinoma of the anus, Capecitabine, Xeloda, Oxaliplatin, Eloxatin, Radiotherapy, XRT

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Capecitabine + Oxaliplatin + XRT
Arm Type
Experimental
Arm Description
Capecitabine (825 mg/m^2 twice a day, Monday-Friday during weeks 1, 2, 4, and 5) and Oxaliplatin (50 mg/m^2, Days 1, 8, 22, 29) during the duration of radiation therapy only. Radiotherapy once daily on days 1-3, 6-10, 13-17, 20-24, 27-31, 34-38, and 41-42. Participants with T3-4 lesions undergo radiotherapy once daily on days 43 and 44. The final dose of radiation therapy determined by the T stage of the primary tumor. Radiotherapy = XRT.
Intervention Type
Drug
Intervention Name(s)
Capecitabine
Other Intervention Name(s)
Xeloda
Intervention Description
825 mg/m^2 orally twice a day (BID), Mon-Fri during weeks 1, 2, 4, and 5.
Intervention Type
Drug
Intervention Name(s)
Oxaliplatin
Other Intervention Name(s)
Eloxatin
Intervention Description
50 mg/m^2 by vein (IV) over 2 hours on days 1, 8, 22, and 29.
Intervention Type
Radiation
Intervention Name(s)
Radiation Therapy (XRT)
Other Intervention Name(s)
XRT, RT, Radiotherapy
Intervention Description
Undergo radiotherapy* once daily on days 1-3, 6-10, 13-17, 20-24, 27-31, 34-38, and 41-42. *Patients with T3-4 lesions undergo radiotherapy once daily on days 43 and 44.
Primary Outcome Measure Information:
Title
2 Year Failure Free Survival
Description
Treatment failure defined as: Biopsy proven residual disease identified 12 -14 weeks after the conclusion of chemoradiation therapy, Treatment-related mortality or Disease recurrence.
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Number of Participants With Complete Response at 2 Years
Description
Response determined by computed tomography (CT)/magnetic resonance imaging (MRI), digital rectal examination, and proctoscopy, and a biopsy performed for clinical suspicion of residual or progressive disease. Response Evaluation Criteria in Solid Tumors (RECIST) where evaluation of target lesions Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): At least a 30% decrease in sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD; Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.
Time Frame
2 Years
Title
Number of Participants With 2-year Colostomy-Free Survival
Description
Colostomy-free survival reported as number of participants who did not develop local recurrence or require salvage resection with colostomy.
Time Frame
2 Years with median study follow up of 19 months
Title
2-year Local Regional Control
Time Frame
2 Years
Title
2-Year Median Overall Survival
Time Frame
2 Years
Title
Number of Participants With Progression-Free Survival at 2-Year
Time Frame
2 Years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Previously untreated patients with histologically proven squamous cell carcinoma of the anal canal. American Joint Committee on Cancer (AJCC) stage II-IIIB (TX 1-4, NX, MO). Age >/= 16 yrs old. Eastern Cooperative Oncology Group (ECOG) Performance Scale (PS) 0-1. Adequate organ function including: Absolute neutrophil Count (ANC) >/= 1,500/uL, Platelets >/= 100,000/uL, Total bilirubin </= 1.5 * upper limit of normal (ULN), aspartate aminotransferase (AST or SGOT)/alanine aminotransferase (ALT or SGPT) </= 3 * ULN, Creatinine </= 1.5mg/dL or Creatinine Clearance (CrCL) >/= 50 cc/min. Patients may have measurable or non-measurable disease. Patients with measurable disease, as defined by the modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria, have at least one lesion that can be accurately measured in at least one dimension with longest diameter to be recorded >/= 20 mm using conventional techniques or >/= 10 mm with spiral CT scan (with minimum lesion size no less than double the slice thickness). Lesions seen on colonoscopy or barium studies are not considered measurable lesions. A negative pregnancy test in all women of child-bearing potential, within two weeks of initiating treatment. The effects of oxaliplatin and capecitabine on the developing human fetus at the recommended therapeutic dose are unknown. For this reason and because cytotoxic agents are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Ability to understand and the willingness to sign the written informed consent/authorization document. Exclusion Criteria: Prior chemotherapy with oxaliplatin, capecitabine, or 5-fluorouracil. Prior radiation to the pelvis. Prior surgery for anal cancer excluding prior biopsy. Known history of dihydropyrimidine (DPD) deficiency. Known history of hypersensitivity to platinum-containing compounds. Peripheral neuropathy of >/= grade 2 by Common Terminology Criteria for Adverse Events (CTCAE) 3.0. Calculated creatinine clearance (CrCl) < 50 cc/min. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit adherence with study requirements. Gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for intravenous (IV) alimentation. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with oxaliplatin or capecitabine, breast feeding should be discontinued. Because of the known interaction of capecitabine and coumadin, patients taking coumadin will be ineligible. Patients will be requested to discontinue coumadin and utilize Lovenox if agreeable. Patients must have discontinued coumadin for 7 days before initiating therapy. No prior malignancies (excluding non-melanomatous skin neoplasms) over the past 5 years. HIV-positive patients receiving combination anti-retroviral therapy are excluded from this study because of possible pharmacokinetic interactions with capecitabine or oxaliplatin. This exclusion is for patient safety since patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy, and because very few HIV-positive anal canal cancer patients are seen at this institution. This hinders us from accruing enough patients to adequately test the safety of this regimen in this population. Patients with symptomatic pulmonary fibrosis.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Cathy Eng, MD
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Christopher H. Crane, MD
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Study Chair
Facility Information:
Facility Name
M. D. Anderson Cancer Center at University of Texas
City
Houston
State/Province
Texas
ZIP/Postal Code
77030-4009
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
31350201
Citation
Eng C, Jacome AA, Das P, Chang GJ, Rodriguez-Bigas M, Skibber JM, Wolff RA, Qiao W, Xing Y, Sethi S, Ohinata A, Crane CH. A Phase II Study of Capecitabine/Oxaliplatin With Concurrent Radiotherapy in Locally Advanced Squamous Cell Carcinoma of the Anal Canal. Clin Colorectal Cancer. 2019 Dec;18(4):301-306. doi: 10.1016/j.clcc.2019.06.003. Epub 2019 Jul 2.
Results Reference
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Capecitabine, Oxaliplatin, and Radiation Therapy in Treating Patients With Stage II or Stage III Anal Cancer

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