Rectal Mucinous AdenocarcinomaPhase 2NCT00745134
Radiation Therapy and Capecitabine With or Without Curcumin Before Surgery in Treating Patients With Rectal Cancer
A Phase 2 study testing Capecitabine, Curcumin and Laboratory Biomarker Analysis in people with Rectal Mucinous Adenocarcinoma and Rectal Signet Ring Cell Adenocarcinoma, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rectal Mucinous Adenocarcinoma, Rectal Signet Ring Cell Adenocarcinoma, Recurrent Rectal Carcinoma
- What is being tested?
- Capecitabine, Curcumin and Laboratory Biomarker Analysis
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 22 participants
- Where
- 1 siteUnited States
- Study dates
- 11 Aug 2008to 11 Nov 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized Double Blinded Study of Curcumin With Pre-operative Capecitabine and Radiation Therapy Followed by Surgery for Rectal Cancer
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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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
- Being tested
- Capecitabine, Curcumin, Laboratory Biomarker Analysis, Pharmacological Study, Placebo
- Medical subject headings
- Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CapecitabineDrug
Also called Ro 09-1978/000, Xeloda
Given PO
CurcuminDietary supplement
Also called C.I. 75300, C.I. Natural Yellow 3, Diferuloylmethane, Turmeric Yellow
Given PO
Laboratory Biomarker AnalysisOther
Correlative studies
Optional correlative studies
PlaceboOther
Also called placebo therapy, PLCB, sham therapy
Given PO
Quality-of-Life AssessmentOther
Also called Quality of Life Assessment
Ancillary studies
Radiation TherapyRadiation
Also called Cancer Radiotherapy, Irradiate, Irradiated, irradiation
Undergo radiation therapy
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Capecitabine; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Other: Placebo; Other: Quality-of-Life Assessment; Radiation: Radiation Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Pathologic Complete Response (pCR) Rate
Compared the rate of pCR between treatment arms with Fisher's exact test.
Measured: At time of surgery
Secondary outcomes (6)
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.
Measured: Baseline to 11.5 weeks
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)
Measured: assessed 1 hr pre/post curcumin administration on one of the days during week 2 of radiation therapy (fractions 6-10)
Tumor Regression Grade
tumor regression grade (1= pCR, 2= near pCR, 3= partial response, 4= no response, 5=progression).
Measured: Baseline to 11.5 weeks
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.
Measured: 5 years
Progression Free Survival (PFS)
PFS was calculated from start of CRT to date of disease progression or death, censored at last endoscopy/imaging evaluation.
Measured: 5 years
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.
Measured: Baseline to 11.5 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Sep 2008 (estimated)
- Study start11 Aug 2008
- Primary completion11 Nov 2022
- Study completion11 Nov 2022
Why it stopped: The trial was stopped early because there was only one patient with pCR among the first 15 patients randomized to the curcumin arm.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Rectal Mucinous AdenocarcinomaStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Jillian R. Gunther, PHD, Study chair, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00745134
- Sponsor's protocol ID
- 2006-0644
- Other IDs
- NCI-2012-01676, 2006-0644
- Status last verified
- Sep 2023
- First submitted
- 2 Sep 2008
- Last updated
- 28 Sep 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 36636059
Study at a glance
From the registry record, last updated by the sponsor on 28 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Double Blinded Study of Curcumin With Pre-operative Capecitabine and Radiation Therapy Followed by Surgery for Rectal Cancer
- ClinicalTrials.gov ID
- NCT00745134
- Acronym / sponsor ID
- 2006-0644
- 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
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The trial was stopped early because there was only one patient with pCR among the first 15 patients randomized to the curcumin arm.
- Enrolment
- 22 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 11 Aug 2008 (actual)
- Primary completion
- 11 Nov 2022 (actual)
- Study completion
- 11 Nov 2022 (actual)
- First posted
- 3 Sep 2008 (estimated)
- Results
- Posted 28 Sep 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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:
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I (curcumin) | Experimental | Drug: Capecitabine, Dietary Supplement: Curcumin, Other: Laboratory Biomarker Analysis, Other: Pharmacological Study, Other: Quality-of-Life Assessment, Radiation: Radiation TherapyPatients 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 II (placebo) | Active comparator | Drug: Capecitabine, Other: Laboratory Biomarker Analysis, Other: Pharmacological Study, Other: Placebo, Other: Quality-of-Life Assessment, Radiation: Radiation TherapyPatients undergo radiation therapy and receive capecitabine as in Arm I. Patients also receive placebo PO BID in weeks 1-11.5. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CapecitabineAlso: Ro 09-1978/000, XelodaGiven PO | Drug | Arm I (curcumin), Arm II (placebo) |
| CurcuminAlso: C.I. 75300, C.I. Natural Yellow 3, Diferuloylmethane, Turmeric YellowGiven PO | Dietary supplement | Arm I (curcumin) |
| Laboratory Biomarker AnalysisCorrelative studies | Other | Arm I (curcumin), Arm II (placebo) |
| Pharmacological StudyOptional correlative studies | Other | Arm I (curcumin), Arm II (placebo) |
| PlaceboAlso: placebo therapy, PLCB, sham therapyGiven PO | Other | Arm II (placebo) |
| Quality-of-Life AssessmentAlso: Quality of Life AssessmentAncillary studies | Other | Arm I (curcumin), Arm II (placebo) |
| Radiation TherapyAlso: Cancer Radiotherapy, Irradiate, Irradiated, irradiationUndergo radiation therapy | Radiation | Arm I (curcumin), Arm II (placebo) |
Primary outcome
Number of Participants With Pathologic Complete Response (pCR) Rate
Time frame: At time of surgery
Compared the rate of pCR between treatment arms with Fisher's exact test.
6 secondary outcomes
Change in Curcumin Level in Tumor Tissue
Time frame: Baseline to 11.5 weeks
Change in Curcumin Level in Serum
Time frame: assessed 1 hr pre/post curcumin administration on one of the days during week 2 of radiation therapy (fractions 6-10)
Tumor Regression Grade
Time frame: Baseline to 11.5 weeks
Overall Survival (OS)
Time frame: 5 years
Progression Free Survival (PFS)
Time frame: 5 years
Number of Participants With Tumor Downstaging
Time frame: Baseline to 11.5 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Sep 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36636059Gunther 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.
- MD Anderson Cancer Center WebsiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jillian R. Gunther, PHD study chair
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Capecitabine, Curcumin and Laboratory Biomarker Analysis in people with Rectal Mucinous Adenocarcinoma and Rectal Signet Ring Cell Adenocarcinoma, run by M.D. Anderson Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 28 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Sep 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Pathologic Complete Response (pCR) Rate (time frame: At time of surgery). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00745134, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Sep 2023.