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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00745134
Recruitment Status : Active, not recruiting
First Posted : September 3, 2008
Last Update Posted : October 22, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

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
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 Drug: Capecitabine Dietary Supplement: Curcumin Other: Laboratory Biomarker Analysis Other: Pharmacological Study Other: Placebo Other: Quality-of-Life Assessment Radiation: Radiation Therapy Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 45 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized Double Blinded Study of Curcumin With Pre-operative Capecitabine and Radiation Therapy Followed by Surgery for Rectal Cancer
Actual Study Start Date : August 11, 2008
Estimated Primary Completion Date : July 31, 2019
Estimated Study Completion Date : July 31, 2019

Resource links provided by the National Library of Medicine


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:
  • Ro 09-1978/000
  • Xeloda

Dietary Supplement: Curcumin
Given PO
Other Names:
  • C.I. 75300
  • C.I. Natural Yellow 3
  • Diferuloylmethane
  • Turmeric Yellow

Other: Laboratory Biomarker Analysis
Correlative studies

Other: Pharmacological Study
Optional correlative studies

Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment

Radiation: Radiation Therapy
Undergo radiation therapy
Other Names:
  • Cancer Radiotherapy
  • Irradiate
  • Irradiated
  • irradiation
  • Radiation
  • Radiotherapeutics
  • RADIOTHERAPY
  • RT
  • Therapy, Radiation

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:
  • Ro 09-1978/000
  • Xeloda

Other: Laboratory Biomarker Analysis
Correlative studies

Other: Pharmacological Study
Optional correlative studies

Other: Placebo
Given PO
Other Names:
  • placebo therapy
  • PLCB
  • sham therapy

Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment

Radiation: Radiation Therapy
Undergo radiation therapy
Other Names:
  • Cancer Radiotherapy
  • Irradiate
  • Irradiated
  • irradiation
  • Radiation
  • Radiotherapeutics
  • RADIOTHERAPY
  • RT
  • Therapy, Radiation




Primary Outcome Measures :
  1. Pathologic complete response (pCR) rate [ Time Frame: At time of surgery ]

Secondary Outcome Measures :
  1. Change in curcumin level in tumor tissue [ Time Frame: 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.

  2. Change in curcumin level in serum [ Time Frame: 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.

  3. Change in quality of life (QoL) as assessed by MD Anderson Symptom Inventory-Gastrointestinal (MDASI-GI) [ Time Frame: 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".

  4. Change in quality of life (QoL) as assessed by Brief Fatigue Inventory (BFI) [ Time Frame: 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".



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00745134


Locations
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United States, Texas
M D Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Sunil Krishnan M.D. Anderson Cancer Center

Additional Information:
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00745134     History of Changes
Other Study ID Numbers: 2006-0644
NCI-2012-01676 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2006-0644 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
First Posted: September 3, 2008    Key Record Dates
Last Update Posted: October 22, 2018
Last Verified: October 2018

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Adenocarcinoma
Rectal Neoplasms
Adenocarcinoma, Mucinous
Cystadenocarcinoma
Carcinoma, Signet Ring Cell
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Neoplasms, Cystic, Mucinous, and Serous
Curcumin
Capecitabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents