Radiation Therapy and Capecitabine With or Without Curcumin Before Surgery in Treating Patients With Rectal Cancer
Study Details
Study Description
Brief Summary
This randomized phase II trial studies how well radiation therapy and capecitabine with or without curcumin before surgery works in treating patients with rectal cancer. Drugs such as curcumin may make tumor cells more sensitive to radiation therapy. Drugs used in chemotherapy, such as capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving chemotherapy with radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. It is not yet known whether chemotherapy and radiation therapy is more effective with or without curcumin when given before surgery in patients with rectal cancer.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
PRIMARY OBJECTIVES:
- To evaluate the efficacy of a combination of capecitabine and radiation therapy with or without curcumin in locally advanced rectal cancer as assessed by pathological complete response rate.
SECONDARY OBJECTIVES:
-
To determine downstaging, local control, disease-free survival and overall survival rates.
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To determine serum and rectal tumor tissue pharmacology of curcumin and its metabolites in the above patients and its correlation with clinical response.
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To identify surrogate molecular markers for curcumin effects. IV. To correlate serum cytokine levels with quality of life in patients receiving this therapy.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients undergo radiation therapy 5 days a week for a total of 28 fractions. Patients also receive capecitabine orally (PO) twice daily (BID) on the days of radiation therapy and curcumin PO BID in weeks 1-11.5.
ARM II: Patients undergo radiation therapy and receive capecitabine as in Arm I. Patients also receive placebo PO BID in weeks 1-11.5.
After completion of study treatment, patients are followed up at 1 month.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Arm I (curcumin) Patients undergo radiation therapy 5 days a week for a total of 28 fractions. Patients also receive capecitabine PO BID on the days of radiation therapy and curcumin PO BID in weeks 1-11.5. |
Drug: Capecitabine
Given PO
Other Names:
Dietary Supplement: Curcumin
Given PO
Other Names:
Other: Laboratory Biomarker Analysis
Correlative studies
Other: Pharmacological Study
Optional correlative studies
Other: Quality-of-Life Assessment
Ancillary studies
Other Names:
Radiation: Radiation Therapy
Undergo radiation therapy
Other Names:
|
| Active Comparator: Arm II (placebo) Patients undergo radiation therapy and receive capecitabine as in Arm I. Patients also receive placebo PO BID in weeks 1-11.5. |
Drug: Capecitabine
Given PO
Other Names:
Other: Laboratory Biomarker Analysis
Correlative studies
Other: Pharmacological Study
Optional correlative studies
Other: Placebo
Given PO
Other Names:
Other: Quality-of-Life Assessment
Ancillary studies
Other Names:
Radiation: Radiation Therapy
Undergo radiation therapy
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Pathologic complete response (pCR) rate [At time of surgery]
Secondary Outcome Measures
- Change in curcumin level in tumor tissue [Baseline to 11.5 weeks]
A logistic regression model with pCR as the dependent variable will be used to assess the association between pCR and NF-kB activity and treatment.
- Change in curcumin level in serum [Baseline to 11.5 weeks]
A logistic regression model with pCR as the dependent variable will be used to assess the association between pCR and NF-kB activity and treatment.
- Change in quality of life (QoL) as assessed by MD Anderson Symptom Inventory-Gastrointestinal (MDASI-GI) [Baseline to 11.5 weeks]
MD Anderson Symptom Inventory-Gastrointestinal (MDASI-GI) symptom scale ranges from 0 meaning "Not Present" to 10 meaning " As Bad as You Can Imagine".
- Change in quality of life (QoL) as assessed by Brief Fatigue Inventory (BFI) [Baseline to 11.5 weeks]
Brief Fatigue Inventory (BFI) scale ranges from 0 meaning "No Fatigue" to 10 meaning "As Bad as You Can Imagine".
Eligibility Criteria
Criteria
Inclusion Criteria:
-
All patients must have clinical stage T3,4 N0,1,2 or T2N1,2 adenocarcinoma of the rectum; patients will be clinically staged using endorectal ultrasound, pelvic computed tomography (CT) or magnetic resonance imaging (MRI), and physical examination
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Histology must be confirmed with review by the Department of Pathology at MD Anderson Cancer Center (MDACC)
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All patients must have no distant metastatic disease in the liver, peritoneum, lungs, or paraaortic lymph nodes
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Patients must have a performance status (Karnofsky scale) of 70% or greater
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Absolute neutrophil count (ANC) > 1200 cells/mm^3
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Platelets > 100,000/mm^3
-
Total serum bilirubin < 2 mg/dl
-
Blood urea nitrogen (BUN) < 30 mg/dl
-
Creatinine < 1.5 mg/dl or creatinine clearance > 50cc/min (estimated as calculated with Cockcroft-Gault equation)
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Patients must have signed informed consent indicating that they are aware of the investigational nature of the study, and are aware that participation is voluntary; patients must also agree to refrain from use of additional herbal supplements during the course of the study
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Patients will agree to continue contraception for 30 days from the date of the last study drug administration; sexually active males must practice contraception during the study
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Postmenopausal woman must have been amenorrheic for at least 12 months to be considered of non-childbearing potential
Exclusion Criteria:
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Prior complete course up to 5 Gy of radiotherapy to the pelvis
-
Pregnant or lactating woman; women of childbearing potential who have not undergone a hysterectomy with either a positive or no pregnancy test at baseline; women / men of childbearing potential not using a reliable and appropriate contraceptive method (oral, injectable, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or vasectomized partner)
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Treatment for other carcinomas within the last five years, except cured non-melanoma skin and treated in-situ cervical cancer
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Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or requiring IV antibiotics, cardiac disease New York Heart Association (NYHA) class III or IV, unstable angina pectoris, unstable cardiac arrhythmia or tachycardia (heart rate > 100 beats/minute), or psychiatric illness/ social situations that would limit compliance with the study requirements are excluded
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Other serious uncontrolled medical conditions that the investigator feels might compromise study participation
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Major surgery within 4 weeks of the start of study treatment
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Prior unanticipated severe reaction to fluoropyrimidine therapy or known hypersensitivity to 5-fluorouracil or capecitabine or curcumin
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Concurrent use of Coumadin other than low dose (1 mg) Coumadin used for line patency; patients on Coumadin must be changed to Lovenox at least 1 week prior to starting capecitabine
-
Concurrent use of cimetidine, allopurinol, or aluminium hydroxide and magnesium hydroxide-containing antacids such as Maalox
-
Sorivudine and brivudine use within 4 weeks of the start of study treatment
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | M D Anderson Cancer Center | Houston | Texas | United States | 77030 |
Sponsors and Collaborators
- M.D. Anderson Cancer Center
- National Cancer Institute (NCI)
Investigators
- Study Chair: Jillian R. Gunther, PHD, M.D. Anderson Cancer Center
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- 2006-0644
- NCI-2012-01676
- 2006-0644