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

Primary Purpose

Rectal Mucinous Adenocarcinoma, Rectal Signet Ring Cell Adenocarcinoma, Recurrent Rectal Carcinoma

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Capecitabine
Curcumin
Laboratory Biomarker Analysis
Pharmacological Study
Placebo
Quality-of-Life Assessment
Radiation Therapy
Sponsored by
M.D. Anderson Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Rectal Mucinous Adenocarcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • M D Anderson Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Arm I (curcumin)

Arm II (placebo)

Arm Description

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.

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

Outcomes

Primary Outcome Measures

Number of Participants With Pathologic Complete Response (pCR) Rate
Compared the rate of pCR between treatment arms with Fisher's exact test.

Secondary Outcome Measures

Change in Curcumin Level in Tumor Tissue
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
Plasma levels were assessed pre and post curcumin/placebo administration. During week 2 (after at least 5 fractions of radiation therapy) of chemoradiation therapy: Optional endoscopic biopsy Optional blood collection for pharmacology (1 hour before and 1 hour after intake of curcumin or placebo)
Tumor Regression Grade
tumor regression grade (1= pCR, 2= near pCR, 3= partial response, 4= no response, 5=progression).
Overall Survival (OS)
OS was calculated from start of CRT to date of death, censored at last follow-up. Estimated with the Kaplan-Meier method.
Progression Free Survival (PFS)
PFS was calculated from start of CRT to date of disease progression or death, censored at last endoscopy/imaging evaluation.
Number of Participants With Tumor Downstaging
Tumor downstaging (DS) is defined as a decrease in the T stage of the primary tumor by at least 1.

Full Information

First Posted
September 2, 2008
Last Updated
September 26, 2023
Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00745134
Brief Title
Radiation Therapy and Capecitabine With or Without Curcumin Before Surgery in Treating Patients With Rectal Cancer
Official Title
A Randomized Double Blinded Study of Curcumin With Pre-operative Capecitabine and Radiation Therapy Followed by Surgery for Rectal Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Terminated
Why Stopped
The trial was stopped early because there was only one patient with pCR among the first 15 patients randomized to the curcumin arm.
Study Start Date
August 11, 2008 (Actual)
Primary Completion Date
November 11, 2022 (Actual)
Study Completion Date
November 11, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
22 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm I (curcumin)
Arm Type
Experimental
Arm Description
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.
Arm Title
Arm II (placebo)
Arm Type
Active Comparator
Arm Description
Patients undergo radiation therapy and receive capecitabine as in Arm I. Patients also receive placebo PO BID in weeks 1-11.5.
Intervention Type
Drug
Intervention Name(s)
Capecitabine
Other Intervention Name(s)
Ro 09-1978/000, Xeloda
Intervention Description
Given PO
Intervention Type
Dietary Supplement
Intervention Name(s)
Curcumin
Other Intervention Name(s)
C.I. 75300, C.I. Natural Yellow 3, Diferuloylmethane, Turmeric Yellow
Intervention Description
Given PO
Intervention Type
Other
Intervention Name(s)
Laboratory Biomarker Analysis
Intervention Description
Correlative studies
Intervention Type
Other
Intervention Name(s)
Pharmacological Study
Intervention Description
Optional correlative studies
Intervention Type
Other
Intervention Name(s)
Placebo
Other Intervention Name(s)
placebo therapy, PLCB, sham therapy
Intervention Description
Given PO
Intervention Type
Other
Intervention Name(s)
Quality-of-Life Assessment
Other Intervention Name(s)
Quality of Life Assessment
Intervention Description
Ancillary studies
Intervention Type
Radiation
Intervention Name(s)
Radiation Therapy
Other Intervention Name(s)
Cancer Radiotherapy, Irradiate, Irradiated, irradiation, Radiation, Radiotherapeutics, RADIOTHERAPY, RT, Therapy, Radiation
Intervention Description
Undergo radiation therapy
Primary Outcome Measure Information:
Title
Number of Participants With Pathologic Complete Response (pCR) Rate
Description
Compared the rate of pCR between treatment arms with Fisher's exact test.
Time Frame
At time of surgery
Secondary Outcome Measure Information:
Title
Change in Curcumin Level in Tumor Tissue
Description
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.
Time Frame
Baseline to 11.5 weeks
Title
Change in Curcumin Level in Serum
Description
Plasma levels were assessed pre and post curcumin/placebo administration. During week 2 (after at least 5 fractions of radiation therapy) of chemoradiation therapy: Optional endoscopic biopsy Optional blood collection for pharmacology (1 hour before and 1 hour after intake of curcumin or placebo)
Time Frame
assessed 1 hr pre/post curcumin administration on one of the days during week 2 of radiation therapy (fractions 6-10)
Title
Tumor Regression Grade
Description
tumor regression grade (1= pCR, 2= near pCR, 3= partial response, 4= no response, 5=progression).
Time Frame
Baseline to 11.5 weeks
Title
Overall Survival (OS)
Description
OS was calculated from start of CRT to date of death, censored at last follow-up. Estimated with the Kaplan-Meier method.
Time Frame
5 years
Title
Progression Free Survival (PFS)
Description
PFS was calculated from start of CRT to date of disease progression or death, censored at last endoscopy/imaging evaluation.
Time Frame
5 years
Title
Number of Participants With Tumor Downstaging
Description
Tumor downstaging (DS) is defined as a decrease in the T stage of the primary tumor by at least 1.
Time Frame
Baseline to 11.5 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jillian R. Gunther, PHD
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Study Chair
Facility Information:
Facility Name
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Links:
URL
http://www.mdanderson.org
Description
MD Anderson Cancer Center Website

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

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