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

• ClinicalTrials.gov Identifier: NCT00093379
• Recruitment Status: Completed
• First Posted: October 8, 2004
• Results First Posted: April 17, 2014
• Last Update Posted: April 17, 2014
• Sponsor: M.D. Anderson Cancer Center
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): M.D. Anderson Cancer Center

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.

Condition or disease	Intervention/treatment	Phase
Anal Cancer	Drug: Capecitabine; Drug: Oxaliplatin; Radiation: Radiation Therapy (XRT)	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 20 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Start Date: April 2004
• Actual Primary Completion Date: July 2012
• Actual Study Completion Date: July 2012

Arms and Interventions

Arm

Intervention/treatment

Experimental: Capecitabine + Oxaliplatin + XRT; 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.

Drug: Capecitabine; 825 mg/m^2 orally twice a day (BID), Mon-Fri during weeks 1, 2, 4, and 5.; Other Name: Xeloda; Drug: Oxaliplatin; 50 mg/m^2 by vein (IV) over 2 hours on days 1, 8, 22, and 29.; Other Name: Eloxatin; Radiation: Radiation Therapy (XRT); 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.; Other Names: XRT; RT; Radiotherapy

Outcome Measures

Primary Outcome Measures :

1. 2 Year Failure Free Survival [ Time Frame: 2 years ]
   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 :

1. Number of Participants With Complete Response at 2 Years [ Time Frame: 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.
2. Number of Participants With 2-year Colostomy-Free Survival [ Time Frame: 2 Years with median study follow up of 19 months ]
   Colostomy-free survival reported as number of participants who did not develop local recurrence or require salvage resection with colostomy.
3. 2-year Local Regional Control [ Time Frame: 2 Years ]
4. 2-Year Median Overall Survival [ Time Frame: 2 Years ]
5. Number of Participants With Progression-Free Survival at 2-Year [ Time Frame: 2 Years ]

Eligibility Criteria

• Ages Eligible for Study: 16 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Previously untreated patients with histologically proven squamous cell carcinoma of the anal canal.
2. American Joint Committee on Cancer (AJCC) stage II-IIIB (TX 1-4, NX, MO).
3. Age >/= 16 yrs old.
4. Eastern Cooperative Oncology Group (ECOG) Performance Scale (PS) 0-1.
5. 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.
6. 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.
7. A negative pregnancy test in all women of child-bearing potential, within two weeks of initiating treatment.
8. 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.
9. Ability to understand and the willingness to sign the written informed consent/authorization document.

Exclusion Criteria:

1. Prior chemotherapy with oxaliplatin, capecitabine, or 5-fluorouracil.
2. Prior radiation to the pelvis.
3. Prior surgery for anal cancer excluding prior biopsy.
4. Known history of dihydropyrimidine (DPD) deficiency.
5. Known history of hypersensitivity to platinum-containing compounds.
6. Peripheral neuropathy of >/= grade 2 by Common Terminology Criteria for Adverse Events (CTCAE) 3.0.
7. Calculated creatinine clearance (CrCl) < 50 cc/min.
8. 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.
9. Gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for intravenous (IV) alimentation.
10. 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.
11. 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.
12. No prior malignancies (excluding non-melanomatous skin neoplasms) over the past 5 years.
13. 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.
14. Patients with symptomatic pulmonary fibrosis.

Contacts and Locations

Locations

United States, Texas

M. D. Anderson Cancer Center at University of Texas

Houston, Texas, United States, 77030-4009

Sponsors and Collaborators

M.D. Anderson Cancer Center

National Cancer Institute (NCI)

Investigators

• Study Chair: Cathy Eng, MD; M.D. Anderson Cancer Center
• Study Chair: Christopher H. Crane, MD; M.D. Anderson Cancer Center

More Information

Additional Information:

The University of Texas (UT) MD Anderson Cancer Center Website 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Eng C, Jácome 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.

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT00093379
• Other Study ID Numbers: 2003-0874; P30CA016672 ( U.S. NIH Grant/Contract ); MDA-2003-0874 ( Other Identifier: UT MD Anderson Cancer Center ); SANOFI-MDA-2003-0874; CDR0000380771 ( Registry Identifier: NCI PDQ )
• First Posted: October 8, 2004
• Results First Posted: April 17, 2014
• Last Update Posted: April 17, 2014
• Last Verified: March 2014

Keywords provided by M.D. Anderson Cancer Center:

stage II anal cancer; stage IIIA anal cancer; stage IIIB anal cancer; squamous cell carcinoma of the anus; Capecitabine; Xeloda; Oxaliplatin; Eloxatin; Radiotherapy; XRT

Additional relevant MeSH terms:

Anus Neoplasms; Rectal Neoplasms; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Anus Diseases; Rectal Diseases; Capecitabine; Oxaliplatin; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents