Curcumin With Pre-operative Capecitabine and Radiation Therapy Followed by Surgery for Rectal Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00745134
First received: September 2, 2008
Last updated: November 20, 2013
Last verified: November 2013

September 2, 2008
November 20, 2013
July 2008
July 2015   (final data collection date for primary outcome measure)
Pathologic Complete Response (pCR) rate [ Time Frame: 18 weeks of treatment prior to surgery, pCR rate evaluated at the time of surgery ] [ Designated as safety issue: Yes ]
The goal of this clinical research study is to learn if combining a curcumin preparation with standard radiation therapy and chemotherapy (capecitabine) can help to shrink or slow the growth of rectal cancer. [ Time Frame: 2 Years ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00745134 on ClinicalTrials.gov Archive Site
Not Provided
The safety of this combination and whether curcumin can help to decrease some of the side effects of standard radiotherapy and chemotherapy will also be studied. [ Time Frame: 2 Years ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
Curcumin With Pre-operative Capecitabine and Radiation Therapy Followed by Surgery for Rectal Cancer
A Randomized Double Blinded Study of Curcumin With Pre-operative Capecitabine and Radiation Therapy Followed by Surgery for Rectal Cancer

The goal of this clinical research study is to learn if combining a curcumin preparation with standard radiation therapy and chemotherapy (capecitabine) can help to shrink or slow the growth of rectal cancer. The safety of this combination and whether curcumin can help to decrease some of the side effects of standard radiotherapy and chemotherapy will also be studied.

The Study Therapy:

Radiation therapy and capecitabine are commonly used treatments for rectal cancer.

Curcumin is the active ingredient in the spice, turmeric, which is commonly used in Indian cooking. Researchers hope the curcumin will interfere with the coping mechanism that cancer cells use to avoid being killed by radiation, thus allowing the radiation to have a greater likelihood of killing the cancer cells.

Study Therapy Administration:

If you are found to be eligible to take part in this study, you will receive radiation therapy once a day, for 5 days in a row (Monday-Friday) for 5-6 weeks (up to 28 treatments in all). You will take capecitabine capsules by mouth twice a day, at morning and night, on each of the days that you receive radiation therapy. These capsules will not be taken on Saturday or Sunday. These capsules should be taken within 30 minutes after eating and with a full glass of water, but not with fruit juice.

You will also be randomly assigned (as in the roll of dice) to one of two groups. Participants in one group will receive additional treatment with a curcumin preparation. Participants in the other group will receive a placebo. The placebo is a substance that looks like curcumin but has no active ingredients. You have a 2 in 3 chance of getting curcumin. This means that for every 3 participants enrolled, 2 will get curcumin and 1 will get placebo. Neither you nor your doctor will know to which group you are assigned.

You will take curcumin/placebo capsules by mouth twice a day, every day that you receive chemotherapy and radiation therapy, on an empty stomach. The first dose of the day should be taken about 1 hour before radiation therapy and the second dose should be taken later in the evening. These capsules must be taken on Saturday and Sunday as well. The placebo or curcumin treatment will continue after you complete chemotherapy and radiation therapy and for an additional 6 weeks.

Study Visits:

Every week while you are having chemotherapy and radiation treatments, you will have the following procedures performed:

  • You will have a physical exam.
  • Blood (about 2 tablespoons) will be drawn to check for side effects from chemotherapy and radiation therapy.
  • You will be asked about any side effects you are experiencing.
  • A plain X-ray film will be taken to check if you have been positioned correctly.

Questionnaires:

You will be asked to fill out 2 questionnaires about your symptoms at the time of enrollment, 1 time a week while receiving radiation therapy, and just before surgery. The 2 questionnaires should take a total of about 10 minutes to fill out.

Length of Treatment:

You will receive up to 11 1/2 weeks of curcumin or placebo on this study. You will be taken off study if the disease gets worse or intolerable side effects occur.

End-of-Treatment Visit:

About 6-12 weeks after completing radiation therapy, you will have a follow-up visit. At this visit, you will have a physical exam. Blood (about 2 tablespoons) will be drawn for routine tests. You will be asked about any side effects you are experiencing. You will be evaluated by a surgeon at this time. If the tumor can be surgically removed, you will be offered surgery to remove the tumor, as is standard of care for the disease. In addition, no matter when you had surgery, at about 1 month (+/- 1 week) after finishing the study drug, you will receive a telephone call from the study staff. They will ask you about any side effects you are experiencing that may be related to the study drug.

Your medical record will be reviewed from time to time to check your health status information.

This is an investigational study. Capecitabine, radiation therapy and curcumin are all commercially available. Capecitabine is FDA approved for treating colon cancer after surgery, and for treating rectal cancer (a specific type of colon cancer) that has spread. Radiation therapy is a standard treatment for rectal cancers. The use of curcumin with capecitabine and radiation therapy in this study is investigational. At this time, the combination is being used in research only.

Up to 45 patients will take part in this study. All will be enrolled at M. D. Anderson.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver)
Primary Purpose: Treatment
Rectal Cancer
  • Drug: Curcumin
    4 gm tablets by mouth twice a day
  • Drug: Placebo
    Tablets by mouth twice a day
  • Radiation: Radiotherapy
    45 Gy once a day, for 5 days in a row for 5-6 weeks (up to 28 treatments in all)
    Other Names:
    • Radiation Therapy
    • XRT
  • Drug: Capecitabine
    825 mg/m^2 by mouth twice a day only on days of radiation (Monday through Friday).
    Other Name: Xeloda
  • Active Comparator: Radiotherapy + Capecitabine + Curcumin
    Radiotherapy 45 Gy once a day, for 5 days in a row for 5-6 weeks (up to 28 treatments in all). Capecitabine 825 mg/m^2 by mouth twice a day only on days of radiation (Monday through Friday). Curcumin 4 gm tablets by mouth twice a day.
    Interventions:
    • Drug: Curcumin
    • Radiation: Radiotherapy
    • Drug: Capecitabine
  • Placebo Comparator: Radiotherapy + Capecitabine + Placebo
    Radiotherapy 45 Gy once a day, for 5 days in a row for 5-6 weeks (up to 28 treatments in all). Capecitabine 825 mg/m^2 by mouth twice a day only on days of radiation (Monday through Friday). Placebo tablets by mouth twice a day.
    Interventions:
    • Drug: Placebo
    • Radiation: Radiotherapy
    • Drug: Capecitabine
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
45
Not Provided
July 2015   (final data collection date for primary outcome measure)

Inclusion Criteria:

  1. 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 CT, and physical examination.
  2. Histology must be confirmed with review by the Department of Pathology at MDACC.
  3. All patients must have no distant metastatic disease in the liver, peritoneum, lungs, or paraaortic lymph nodes.
  4. Patients must have a performance status (Karnofsky scale) of 70% or greater.
  5. Patient must be >/= 18 years of age.
  6. Patients must have ANC > 1200 cells/mm^3, platelets > 100,000/mm^3, total serum bilirubin < 2 mg/dl, BUN <30 mg/dl, creatinine < 1.5 mg/dl or creatinine clearance > 50cc/min (estimated as calculated with Cockcroft-Gault equation). Creatinine Clearance (men) = {(140 - age) x lean body weight (in kg.)}/ {Plasma creatinine (mg/dl) x 72} Creatinine Clearance (women) = 0.85 x {(140 - age) x lean body weight (in kg.)}/ {Plasma creatinine (mg/dl) x 72}
  7. 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.
  8. 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.
  9. Postmenopausal woman must have been amenorrheic for at least 12 months to be considered of non-childbearing potential.

Exclusion Criteria:

  1. Prior complete course up to 5 Gy of radiotherapy to the pelvis.
  2. 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).
  3. Treatment for other carcinomas within the last five years, except cured non-melanoma skin and treated in-situ cervical cancer.
  4. Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or requiring IV antibiotics, cardiac disease NYHA class III or IV, unstable angina pectoris, unstable cardiac arrythmia or tachycardia (heart rate > 100 beats/minute), or psychiatric illness/ social situations that would limit compliance with the study requirements are excluded.
  5. Other serious uncontrolled medical conditions that the investigator feels might compromise study participation.
  6. Major surgery within 4 weeks of the start of study treatment.
  7. Prior unanticipated severe reaction to fluoropyrimidine therapy or known hypersensitivity to 5-fluorouracil or capecitabine or curcumin.
  8. 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.
  9. Concurrent use of cimetidine, allopurinol, or aluminium hydroxide and magnesium hydroxide-containing antacids such as Maalox.
  10. Sorivudine and brivudine use within 4 weeks of the start of study treatment.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00745134
2006-0644, P07010
Yes
M.D. Anderson Cancer Center
M.D. Anderson Cancer Center
Not Provided
Principal Investigator: Sunil Krishnan, MD UT MD Anderson Cancer Center
M.D. Anderson Cancer Center
November 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP