Rectal CancerPhase 2NCT00250835
Combination of Oxaliplatin, Capecitabine, and Celecoxib With Concurrent Radiation for Rectal Cancer
A Phase 2 study testing Chemotherapy, Celecoxib, and Radiation in people with Rectal Cancer, run by New Mexico Cancer Research Alliance at 3 sites in United States.
Trial summary
A combination of chemotherapy and radiation is often used to treat rectal cancer patients before surgery in an effort to shrink the tumor and make it easier to remove as well as to help increase the chances of sphincter-sparing surgery. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rectal Cancer
- What is being tested?
- Chemotherapy, Celecoxib, and Radiation
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 38 participants
- Where
- 3 sitesUnited States
- Study dates
- Apr 2005to May 2015
- 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 18 years of age or older, with biopsy proven T3-4N0-2M0 rectal cancer are eligible.
- Life expectancy of at least 2 years.
- Zubrod performance status of 0-2.
- Patients must be able to sign an informed consent.
- Adequate bone marrow function: peripheral granulocyte count of > 1,500 cells/mm3 and platelet count >100,000/mm3, hemoglobin > 10 gm/dl and absence of a regular red blood cell transfusion requirement.
- Adequate hepatic function with a total serum bilirubin < 1.5 x ULN; alkaline phosphatase, alanine aminotransferase (ALAT), and aspartate aminotransferase (ASAT) < 2.5 x the upper limit of normal (ULN); and adequate renal function as defined by a calculated creatinine clearance > 50 ml/min [Cockroft-Gault].
- Other initial cancer diagnosis more than five years ago without evidence of residual or recurrent disease
- Prior diagnosis of squamous or basal cell carcinoma of skin,no active disease at the time of enrollment.
Who cannot join
- Known metastases
- Pregnant or lactating women. Women/men of childbearing potential not using a reliable and appropriate contraceptive method.
- May receive no other concurrent chemotherapy or radiation therapy during this trial.
- Severe medical problems such as uncontrolled diabetes mellitus or cardiovascular disease or active infections
- Prior pelvic radiation
- Known active inflammatory bowel disease, Crohn's disease or ulcerative colitis.
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- Medical conditions that would preclude the patient from definitive surgery at the end of concurrent chemoradiation
- Serious, uncontrolled, concurrent infection(s).
- Prior severe reaction to fluoropyrimidine therapy, or known hyper-sensitivity to 5-fluorouracil or known dihydropyrimidine dehydrogenase (DPD) deficiency.
- Treatment for other carcinomas within the last five years, except cured non-melanoma skin and treated in-situ cervical cancer.
- Participation in any investigational drug study within 4 weeks preceding the start of study treatment.
- Clinically significant cardiac disease or myocardial infarction within the last 12 months.
- History of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant, precluding informed consent, or interfering with compliance of oral drug intake.
- Other serious uncontrolled medical conditions that the investigator feels might compromise study participation.
- Major surgery <4 weeks of the start of study treatment, without complete recovery.
- Lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome.
- Known, existing uncontrolled coagulopathy
- Any of the following laboratory values:
- Abnormal hematologic values (neutrophils < 1.5 x 10^9/L, platelet count < 100 x 10^9/L, hemoglobin < 10 gm/dl)
- Impaired renal function (estimated creatinine clearance <50 ml/min as calculated with Cockroft-Gault equation.
- Serum total bilirubin > 1.5 x upper normal limit.
- ALAT, ASAT > 2.5 x upper normal limit (or > 5 x upper normal limit in the case of liver metastases).
- Alkaline phosphatase > 2.5 x upper normal limit (or > 5 x upper normal limit in the case of liver metastases or > 10 x upper normal limit in the case of bone disease).
- Unwillingness to give written informed consent.
- Unwillingness to participate or inability to comply with the protocol for the duration of the study.
- History of allergic reactions, hypersensitivity reactions to aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), or sulfonamides
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Hematology Oncology Associates
Albuquerque, New Mexico, 87106
University of New Mexico Cancer Center
Albuquerque, New Mexico, 87106
New Mexico Cancer Care Associates
Santa Fe, New Mexico, 87505
About this study
Official title: A Phase II Trial Using a Combination of Oxaliplatin, Capecitabine, and Celecoxib With Concurrent Radiation for Patients With Newly Diagnosed Resectable Rectal Cancer
A combination of chemotherapy and radiation is often used to treat rectal cancer patients before surgery in an effort to shrink the tumor and make it easier to remove as well as to help increase the chances of sphincter-sparing surgery. Many previous clinical studies have suggested that rectal cancer patients may survive longer if the surgery results in a pathological complete response - that is, the absence of any tumor cells in the surgical specimen. However, there is still controversy over this. This study attempts to start to answer this question by treating rectal cancer patients with a combination of chemotherapy drugs (oxaliplatin and capecitabine), a cyclooxygenase-2 (COX-2) enzyme inhibitor and radiation before surgery. The rates of pathologic complete response, sphincter-sparing surgery, and disease-free survival are some of the therapeutic endpoints that will be studied.
Read the detailed description
Improved regional control as demonstrated by a lower incidence of local recurrence after concurrent chemoradiation delivered either pre-operatively or post-operatively for resectable rectal cancer is supported by clinical trial data but the impact on overall survival with either approach remains controversial. An ideal regimen for preoperative chemoradiation in locally advanced rectal cancer would include agents that are both potent radio-sensitizers and effective in treating micro-metastatic disease without excessive toxicity. The cyclooxygenase-2 (COX-2) enzyme is over expressed in colorectal cancer, but the exact role of this over expression in tumorigenesis remains an active area of research. The area with the most potential in using cyclooxygenase-2 inhibitors in cancer treatment may be to use them as an adjunct to other modalities of treatment.
Taking into consideration all the above, a previous pilot trial of neoadjuvant therapy with combined oxaliplatin, capecitabine, celecoxib (a COX-2 inhibitor), and radiation was conducted in four patients with operable rectal cancer. Promising results, including pain relief and downstaging of cancer, were observed.
Therefore, this single-arm phase II trial of preoperative concurrent chemoradiation for patients with T3-4N0-2M0 rectal cancer was initiated to assess patient outcomes and explore the relationship between COX-2 expression in surgical specimens and therapeutic endpoints.
- Conditions
- Rectal Cancer
- Being tested
- Chemotherapy, Celecoxib, and Radiation
- Keywords
- Resectable Rectal Cancer, Radiation, Neoadjuvant, Rectum, GI - Colorectal Neoadjuvant, Cancer
- Medical subject headings
- Rectal Neoplasms, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Chemotherapy, Celecoxib, and RadiationOther
Also called Celecoxib = Celebrex, Oxaliplatin = Eloxatin, Capecitabine = Xeloda
Enrolled rectal cancer patients are treated with concurrent chemoradiation and celecoxib pre-operatively for at least 14 days. Definitive surgery is performed within 6 weeks from the end of treatment.
| Study group | Role | What they receive |
|---|---|---|
| Chemotherapy, Celecoxib, and Radiation | Experimental | Oxaliplatin weekly at 50 mg/m2 given intravenously over two hours for the duration of radiation.
Capecitabine: on the days of radiation at 850 mg/m2 orally twice a day [1700 mg/m2/day] (Monday through Friday during radiation therapy).
Celecoxib at 200 mg orally twice a day throughout the duration of radiation without a break. Receives: Other: Chemotherapy, Celecoxib, and Radiation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pathologic Complete Response (PCR)
The pathologic complete response (PCR) rate will be calculated as the proportion of patients who achieve complete response out of all evaluable patients. PCR is defined as the total absence of residual tumor cells by microscopic examination of the resected surgical specimen, including all of the sampled lymph nodes.
Measured: At surgery (up to 6 weeks after end of treatment)
Secondary outcomes (5)
Toxicity
All toxicities encountered during the study will be evaluated according to the grading system (0-5) NCI CTCAE (Common Terminology Criteria for Adverse Events) version 3.0.
Toxicity will be reported as the proportion of subjects experiencing Grades 3,4, and 5 adverse events (AEs) out of all evaluable patients
Measured: Up to 3 years
Progression-free Survival (PFS)
The Response Evaluation Criteria In Solid Tumors (RECIST) guidelines (Version 1.0) will be used to determine tumor response and progression. Progressive disease (PD) for target lesions: >= 20% increase in the sum of diameters of the target lesions taking as reference the smallest sum on study, and an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered . PD for non-target lesions is defined as unequivocal appearance of one or more new malignant lesions or unequivocal progression of existing non-target lesions. Time to progression will be measured from the time of surgery or clinically documented down staging if surgery for whatever reason is not carried in the subject until there is evidence of PD.
Progression-free survival is reported as the percentage of patients who have not experienced progression of disease at three years post-surgery
Measured: 3 years after surgery
Incidence of Sphincter-sparing Surgery
Incidence of sphincter-saving surgery is defined as the proportion of subjects who do not have permanent colostomy at the final follow-up out of all evaluable patients.
Measured: At surgery (up to 6 weeks after end of treatment)
Surgical Downstaging Rate
Downstaging rate after neoadjuvant treatment with combination oxaliplatin, capecitabine, celecoxib and concurrent radiation is defined as the proportion of patients whose pathological stage (stage at surgery) is different from their clinical stage (stage at baseline)
Measured: At surgery (up to 6 weeks after treatment)
Pelvic Local Control Rate
Pelvic local control rate is defined as the proportion of subjects who have no evidence of pelvic recurrence (by standard clinical assessment, including CT scan and clinical examination) at the final follow-up evaluation, out of all evaluable patients
Measured: Up to 3 years after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Nov 2005 (estimated)
- Study startApr 2005
- Primary completionDec 2012
- Study completionMay 2015
Why it stopped: Low accrual
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 CancerStudies of the same condition, open and under way.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- New Mexico Cancer Research Alliance
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Fa-Chyi Lee, MD, Principal investigator, University of New Mexico
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00250835
- Sponsor's protocol ID
- 3304C
- Other IDs
- NCI-2011-02685
- Status last verified
- Aug 2015
- First submitted
- 4 Nov 2005
- Last updated
- 1 Sep 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Araujo-Mino EP, Patt YZ, Murray-Krezan C, Hanson JA, Bansal P, Liem BJ, Rajput A, Fekrazad MH, Heywood G, Lee FC. Phase II Trial Using a Combination of Oxaliplatin, Capecitabine, and Celecoxib with Concurrent Radiation for Newly Diagnosed Resectable Rectal Cancer. Oncologist. 2018 Jan;23(1):2-e5. doi: 10.1634/theoncologist.2017-0474. Epub 2017 Nov 20.
PubMed 29158365
Study at a glance
From the registry record, last updated by the sponsor on 1 Sep 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Trial Using a Combination of Oxaliplatin, Capecitabine, and Celecoxib With Concurrent Radiation for Patients With Newly Diagnosed Resectable Rectal Cancer
- ClinicalTrials.gov ID
- NCT00250835
- Acronym / sponsor ID
- 3304C
- Conditions
- Rectal Cancer
- Keywords
- Resectable Rectal Cancer, Radiation, Neoadjuvant, Rectum, GI - Colorectal Neoadjuvant, Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low accrual
- Enrolment
- 38 participants (actual)
- Lead sponsor
- New Mexico Cancer Research AllianceUniversity, hospital or other
- Study start
- Apr 2005
- Primary completion
- Dec 2012 (actual)
- Study completion
- May 2015 (actual)
- First posted
- 8 Nov 2005 (estimated)
- Results
- Posted 1 Sep 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A combination of chemotherapy and radiation is often used to treat rectal cancer patients before surgery in an effort to shrink the tumor and make it easier to remove as well as to help increase the chances of sphincter-sparing surgery. Many previous clinical studies have suggested that rectal cancer patients may survive longer if the surgery results in a pathological complete response - that is, the absence of any tumor cells in the surgical specimen. However, there is still controversy over this. This study attempts to start to answer this question by treating rectal cancer patients with a combination of chemotherapy drugs (oxaliplatin and capecitabine), a cyclooxygenase-2 (COX-2) enzyme inhibitor and radiation before surgery. The rates of pathologic complete response, sphincter-sparing surgery, and disease-free survival are some of the therapeutic endpoints that will be studied.
Detailed description
Improved regional control as demonstrated by a lower incidence of local recurrence after concurrent chemoradiation delivered either pre-operatively or post-operatively for resectable rectal cancer is supported by clinical trial data but the impact on overall survival with either approach remains controversial. An ideal regimen for preoperative chemoradiation in locally advanced rectal cancer would include agents that are both potent radio-sensitizers and effective in treating micro-metastatic disease without excessive toxicity. The cyclooxygenase-2 (COX-2) enzyme is over expressed in colorectal cancer, but the exact role of this over expression in tumorigenesis remains an active area of research. The area with the most potential in using cyclooxygenase-2 inhibitors in cancer treatment may be to use them as an adjunct to other modalities of treatment.
Taking into consideration all the above, a previous pilot trial of neoadjuvant therapy with combined oxaliplatin, capecitabine, celecoxib (a COX-2 inhibitor), and radiation was conducted in four patients with operable rectal cancer. Promising results, including pain relief and downstaging of cancer, were observed.
Therefore, this single-arm phase II trial of preoperative concurrent chemoradiation for patients with T3-4N0-2M0 rectal cancer was initiated to assess patient outcomes and explore the relationship between COX-2 expression in surgical specimens and therapeutic endpoints.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Chemotherapy, Celecoxib, and Radiation | Experimental | Other: Chemotherapy, Celecoxib, and RadiationOxaliplatin weekly at 50 mg/m2 given intravenously over two hours for the duration of radiation. Capecitabine: on the days of radiation at 850 mg/m2 orally twice a day [1700 mg/m2/day] (Monday through Friday during radiation therapy). Celecoxib at 200 mg orally twice a day throughout the duration of radiation without a break. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- All patients 18 years of age or older, with biopsy proven T3-4N0-2M0 rectal cancer are eligible.
- Life expectancy of at least 2 years.
- Zubrod performance status of 0-2.
- Patients must be able to sign an informed consent.
- Adequate bone marrow function: peripheral granulocyte count of > 1,500 cells/mm3 and platelet count >100,000/mm3, hemoglobin > 10 gm/dl and absence of a regular red blood cell transfusion requirement.
Key exclusion criteria (26 listed)
- Known metastases
- Pregnant or lactating women. Women/men of childbearing potential not using a reliable and appropriate contraceptive method.
- May receive no other concurrent chemotherapy or radiation therapy during this trial.
- Severe medical problems such as uncontrolled diabetes mellitus or cardiovascular disease or active infections
- Prior pelvic radiation
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 |
|---|---|---|
| Chemotherapy, Celecoxib, and RadiationAlso: Celecoxib = Celebrex, Oxaliplatin = Eloxatin, Capecitabine = XelodaEnrolled rectal cancer patients are treated with concurrent chemoradiation and celecoxib pre-operatively for at least 14 days. Definitive surgery is performed within 6 weeks from the end of treatment. | Other | Chemotherapy, Celecoxib, and Radiation |
Primary outcome
Pathologic Complete Response (PCR)
Time frame: At surgery (up to 6 weeks after end of treatment)
The pathologic complete response (PCR) rate will be calculated as the proportion of patients who achieve complete response out of all evaluable patients. PCR is defined as the total absence of residual tumor cells by microscopic examination of the resected surgical specimen, including all of the sampled lymph nodes.
5 secondary outcomes
Toxicity
Time frame: Up to 3 years
Progression-free Survival (PFS)
Time frame: 3 years after surgery
Incidence of Sphincter-sparing Surgery
Time frame: At surgery (up to 6 weeks after end of treatment)
Surgical Downstaging Rate
Time frame: At surgery (up to 6 weeks after treatment)
Pelvic Local Control Rate
Time frame: Up to 3 years after surgery
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Sep 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 29158365Araujo-Mino EP, Patt YZ, Murray-Krezan C, Hanson JA, Bansal P, Liem BJ, Rajput A, Fekrazad MH, Heywood G, Lee FC. Phase II Trial Using a Combination of Oxaliplatin, Capecitabine, and Celecoxib with Concurrent Radiation for Newly Diagnosed Resectable Rectal Cancer. Oncologist. 2018 Jan;23(1):2-e5. doi: 10.1634/theoncologist.2017-0474. Epub 2017 Nov 20.
- University of New Mexico Cancer CenterLink provided by the sponsor.
- New Mexico Cancer Care AllianceLink 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.
Fa-Chyi Lee, MD principal investigator
University of New Mexico
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Chemotherapy, Celecoxib, and Radiation in people with Rectal Cancer, run by New Mexico Cancer Research Alliance at 3 sites 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 8 inclusion and 26 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 1 Sep 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites 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 1 Sep 2015). 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?
Pathologic Complete Response (PCR) (time frame: At surgery (up to 6 weeks after end of treatment)). 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 NCT00250835, 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 1 Sep 2015; AzTrials last refreshed its copy on 8 Nov 2026.