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

NCT00745134 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: 2006-0644NCI-2012-01676
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Pathologic Complete Response (pCR) Rate

  Compared the rate of pCR between treatment arms with Fisher's exact test.

  At time of surgery

Secondary Outcomes (6)

• Change in Curcumin Level in Tumor Tissue

  Baseline to 11.5 weeks

• Change in Curcumin Level in Serum

  assessed 1 hr pre/post curcumin administration on one of the days during week 2 of radiation therapy (fractions 6-10)

• Tumor Regression Grade

  Baseline to 11.5 weeks

• Overall Survival (OS)

  5 years

• Progression Free Survival (PFS)

  5 years

Study Arms (2)

Arm I (curcumin)

EXPERIMENTAL

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; Dietary Supplement: Curcumin; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Other: Quality-of-Life Assessment; Radiation: Radiation Therapy

Arm II (placebo)

ACTIVE COMPARATOR

Patients undergo radiation therapy and receive capecitabine as in Arm I. Patients also receive placebo PO BID in weeks 1-11.5.

Drug: Capecitabine; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Other: Placebo; Other: Quality-of-Life Assessment; Radiation: Radiation Therapy

Interventions

Capecitabine DRUG

Given PO

Also known as: Ro 09-1978/000, Xeloda

Arm I (curcumin); Arm II (placebo)

Curcumin DIETARY_SUPPLEMENT

Given PO

Also known as: C.I. 75300, C.I. Natural Yellow 3, Diferuloylmethane, Turmeric Yellow

Arm I (curcumin)

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm I (curcumin); Arm II (placebo)

Pharmacological Study OTHER

Optional correlative studies

Arm I (curcumin); Arm II (placebo)

Placebo OTHER

Given PO

Also known as: placebo therapy, PLCB, sham therapy

Arm II (placebo)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Arm I (curcumin); Arm II (placebo)

Radiation Therapy RADIATION

Undergo radiation therapy

Also known as: Cancer Radiotherapy, Irradiate, Irradiated, irradiation, Radiation, Radiotherapeutics, RADIOTHERAPY, RT, Therapy, Radiation

Arm I (curcumin); Arm II (placebo)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• 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.

  PMID: 36636059 DERIVED

Related Links

• MD Anderson Cancer Center Website

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Capecitabine; Curcumin; Radiotherapy; Radiation

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Diarylheptanoids; Heptanes; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Therapeutics; Physical Phenomena

Results Point of Contact

• Title: Dr. Jillian Gunther
• Organization: M D Anderson Cancer Center

JGunther@mdanderson.org

832-710-7864

Study Officials

• Jillian R. Gunther, PHD

  M.D. Anderson Cancer Center

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 2, 2008
• First Posted: September 3, 2008
• Study Start: August 11, 2008
• Primary Completion: November 11, 2022
• Study Completion: November 11, 2022
• Last Updated: September 28, 2023
• Results First Posted: September 28, 2023

Record last verified: 2023-09

Locations

US (1)