Radiation Therapy and Capecitabine With or Without Curcumin Before Surgery in Treating Patients With Rectal Cancer

NCT ID: NCT00745134

Last Updated: 2023-09-28

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-08-11
• Study Completion Date: 2022-11-11

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.

Detailed Description

PRIMARY OBJECTIVES:

I. 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:

I. To determine downstaging, local control, disease-free survival and overall survival rates.

II. To determine serum and rectal tumor tissue pharmacology of curcumin and its metabolites in the above patients and its correlation with clinical response.

III. 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.

Conditions

Rectal Mucinous Adenocarcinoma; Rectal Signet Ring Cell Adenocarcinoma; Recurrent Rectal Carcinoma; Stage IIA Rectal Cancer AJCC v7; Stage IIB Rectal Cancer AJCC v7; Stage IIC Rectal Cancer AJCC v7; Stage IIIA Rectal Cancer AJCC v7; Stage IIIB Rectal Cancer AJCC v7; Stage IIIC Rectal Cancer AJCC v7

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: EXPERIMENTAL

Capecitabine

Intervention Type: DRUG

Given PO

Curcumin

Intervention Type: DIETARY_SUPPLEMENT

Given PO

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Pharmacological Study

Intervention Type: OTHER

Optional correlative studies

Quality-of-Life Assessment

Intervention Type: OTHER

Ancillary studies

Radiation Therapy

Intervention Type: RADIATION

Undergo radiation therapy

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.

Group Type: ACTIVE_COMPARATOR

Capecitabine

Intervention Type: DRUG

Given PO

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Pharmacological Study

Intervention Type: OTHER

Optional correlative studies

Placebo

Intervention Type: OTHER

Given PO

Quality-of-Life Assessment

Intervention Type: OTHER

Ancillary studies

Radiation Therapy

Intervention Type: RADIATION

Undergo radiation therapy

Interventions

Capecitabine

Given PO

Intervention Type: DRUG

Curcumin

Given PO

Intervention Type: DIETARY_SUPPLEMENT

Laboratory Biomarker Analysis

Correlative studies

Intervention Type: OTHER

Pharmacological Study

Optional correlative studies

Intervention Type: OTHER

Placebo

Given PO

Intervention Type: OTHER

Quality-of-Life Assessment

Ancillary studies

Intervention Type: OTHER

Radiation Therapy

Undergo radiation therapy

Intervention Type: RADIATION

Other Intervention Names

Ro 09-1978/000; Xeloda; C.I. 75300; C.I. Natural Yellow 3; Diferuloylmethane; Turmeric Yellow; placebo therapy; PLCB; sham therapy; Quality of Life Assessment; Cancer Radiotherapy; Irradiate; Irradiated; irradiation; Radiation; Radiotherapeutics; RADIOTHERAPY; RT; Therapy, Radiation

Eligibility 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
• Histology must be confirmed with review by the Department of Pathology at MD Anderson Cancer Center (MDACC)
• All patients must have no distant metastatic disease in the liver, peritoneum, lungs, or paraaortic lymph nodes
• Patients must have a performance status (Karnofsky scale) of 70% or greater
• Absolute neutrophil count (ANC) > 1200 cells/mm^3
• 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)
• 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
• 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
• Postmenopausal woman must have been amenorrheic for at least 12 months to be considered of non-childbearing potential

Exclusion Criteria

• 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)
• Treatment for other carcinomas within the last five years, except cured non-melanoma skin and treated in-situ cervical cancer
• 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
• Other serious uncontrolled medical conditions that the investigator feels might compromise study participation
• Major surgery within 4 weeks of the start of study treatment
• Prior unanticipated severe reaction to fluoropyrimidine therapy or known hypersensitivity to 5-fluorouracil or capecitabine or curcumin
• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

M.D. Anderson Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jillian R. Gunther, PHD

Role: STUDY_CHAIR

M.D. Anderson Cancer Center

Locations

M D Anderson Cancer Center

Houston, Texas, United States

Countries

United States

References

Gunther JR, Chadha AS, Guha S, Raju GS, Maru DM, Munsell MF, Jiang Y, Yang P, Felix E, Clemons M, Mathew GG, Singh PK, Skibber JM, Rodriguez-Bigas MA, Chang GJ, Eng C, Delclos ME, Crane CH, Das P, Krishnan S. A phase II randomized double blinded trial evaluating the efficacy of curcumin with pre-operative chemoradiation for rectal cancer. J Gastrointest Oncol. 2022 Dec;13(6):2938-2950. doi: 10.21037/jgo-22-259.

Reference Type: DERIVED

PMID: 36636059 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

http://www.mdanderson.org

MD Anderson Cancer Center Website

Other Identifiers

NCI-2012-01676

Identifier Type: REGISTRY

Identifier Source: secondary_id

2006-0644

Identifier Type: OTHER

Identifier Source: secondary_id

2006-0644

Identifier Type: -

Identifier Source: org_study_id