Rectal CancerPhase 2NCT00216086
Capecitabine + Irinotecan Followed by Combined Modality Capecitabine and Radiation in Locally Advanced Rectal Cancer
A Phase 2 study testing Capecitabine, Irinotecan and EUS in people with Rectal Cancer, run by Gabi Chiorean, MD at 9 sites in United States.
Trial summary
Preoperative induction chemotherapy has been successfully used in a variety of malignancies and provides several advantages over postoperative therapy. Combination of 5-FU/Leucovorin/CPT-11 has demonstrated significantly better response rate than 5-FU/Leucovorin alone. 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?
- Capecitabine, Irinotecan and EUS
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 9 sitesUnited States
- Study dates
- May 2005to May 2008
- 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
- Histologically confirmed adenocarcinoma of the rectum < 15 cm from the anal verge without evidence of distant metastasis·
- Measurable disease. ·
- Either mobile cancers (with clinical stage T3 or T4 by endorectal ultrasound) or fixed cancer (defined as clinical T4 for this study) on palpation. ·
- Malignant disease may not extend to the anal canal (across the dentate line)
Who cannot join
- No prior chemotherapy or radiation therapy to the pelvis.
- Patients with clinical stage T 1-2, N0 rectal cancer who are candidates for primary resection are not eligible·
- No synchronous colonic cancer unless the synchronous tumor is Tis or T1 and has been completely resected·
- Patients must not be taking warfarin·
- No prior unanticipated severe reaction to fluoropyrimidine therapy, or known sensitivity to 5-Fluorouracil or known DPD deficiency.·
- No known existing uncontrolled coagulopathy·
Show all 11Show fewer
- Negative pregnancy test·
- No current breastfeeding·
- No serious concomitant systemic disorders incompatible with the study· No prior malignancies with the exception of curatively treated basal or squamous carcinoma of the skin, carcinoma in-situ of the cervix, or any other cancer for which the patient has been disease-free for < 5 years.·
- Patients must not be treated with any of the following while on protocol therapy or within 28 days prior to beginning protocol therapy: sorivudine, brivudine, cimetidine, allopurinol.
- Patients on dilantin must have regular monitoring of dilantin levels.
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
United States9 sites
Elkhart Clinic
Elkhart, Indiana, 46515
Fort Wayne Oncology & Hematology, Inc
Fort Wayne, Indiana, 46815
Center for Cancer Care at Goshen Health System
Goshen, Indiana, 46527
Indiana University Cancer Center
Indianapolis, Indiana, 46202
Quality Cancer Center (MCGOP)
Indianapolis, Indiana, 46202
Medical Consultants, P.C.
Muncie, Indiana, 47303
Center for Cancer Care, Inc., P.C.
New Albany, Indiana, 47150
Northern Indiana Cancer Research Consortium
South Bend, Indiana, 46601
AP&S Clinic
Terre Haute, Indiana, 47804
About this study
Official title: A Phase II Trial of Preoperative Capecitabine Plus Irinotecan Followed by Combined Modality Capecitabine and Radiation for Locally Advanced Rectal Cancer: Hoosier Oncology Group GI03-53
Preoperative induction chemotherapy has been successfully used in a variety of malignancies and provides several advantages over postoperative therapy. Combination of 5-FU/Leucovorin/CPT-11 has demonstrated significantly better response rate than 5-FU/Leucovorin alone. Replacing 5-FU with oral capecitabine in combination with CPT-11 has emerged as a potentially more effective, safe and convenient treatment option for metastatic colorectal cancer. Capecitabine is also well tolerated in concurrent treatment with radiation. Recent data has shown that preoperative radiation appears to be significantly more effective in increasing resectability rates.
This trial will investigate the activity of capecitabine and CPT-11 combination in the preoperative setting followed by chemoradiation with capecitabine in locally advanced rectal cancer to improve response and decrease local recurrence. We will also study whether TS, TP, DPD and carboxyesterase expressions correlate with the objective response rate with this chemotherapy and chemoradiation regimen.
Read the detailed description
OUTLINE: This is a multi-center study.
Biopsy per EUS
- Irinotecan 200 mg/m2 IV, day 1
- Capecitabine 1000* mg/m2 PO BID day 1-14 Repeat every three weeks for two cycles* For calculated creatinine clearance of 30-50 mL/min or patients > 70years old, capecitabine starting dose is 825 mg/m2 PO BID
Beginning at week 7 or following recovery from chemotherapy:
- Pelvic XRT 45 Gy/1.8 Gy/fx/qd+5.4 Gy/1.8 Gy/fx/qd for T3+9 Gy/1.8 Gy/fx/qd for T4
- Capecitabine 825* mg/m2 PO BID, 5 days/week, throughout XRT* For calculated creatinine clearance of 30-50 mL/min or patients > 70years old, capecitabine starting dose is 650 mg/m2 PO BID
- Surgery within 8weeks following chemoradiotherapy
- Adjuvant Chemotherapy at investigator's discretion
ECOG performance status 0 or 1
Hematopoietic:·
- ANC count >1,500 mm3·
- Platelets > 100,000/mm3·
- Hemoglobin > 9g/dL
- Prothrombin time (PT)/INR or PTT < 1.25 times upper limit of normal;
Hepatic:·
- Bilirubin <1.5 times upper limit of normal
- Alanine Transaminase (ALT) or Aspartate Transaminase (AST) <2.5 times the upper limit of normal
Renal:·
- Adequate renal function by calculated creatinine clearance > 30 mL/min (by Cockroft and Gault)
Cardiovascular:·
- No congestive heart failure requiring therapy or NYHA class II or greater or active angina or known myocardial infarction within 12 months prior to study
- Conditions
- Rectal Cancer
- Being tested
- Capecitabine, Irinotecan, EUS, Neoadjuvant Chemotherapy, Preoperative Radiation
- Keywords
- Rectal Cancer
- 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 Xeloda
Capecitabine 1000* mg/m2 po bid day 1-14; repeat every three weeks for two cycles
*For calculated creatinine clearance of 30-50 mL/min or patients > 70 years old, capecitabine starting dose is 825 mg/m2 po bid
IrinotecanDrug
Also called Camptosar
Irinotecan 200 mg/m2 IV, day 1
EUSProcedure or surgery
biopsy per EUS
Neoadjuvant ChemotherapyDrug
Also called Camptosar, Xeloda
- Irinotecan 200 mg/m2 IV, day 1
- Capecitabine 1000 mg/m2 po bid day 1-14; repeat every three weeks for two cycles
Preoperative RadiationProcedure or surgery
Pelvic XRT 45 Gy/1.8 GY/fx/qd+5/4 Gy/1.8 Gy/fx/qd for T3+9 Gy/1.8/Gy/fx/qd for T4
SurgeryProcedure or surgery
Surgery within 8 weeks following chemoradiotherapy
Adjuvant ChemotherapyProcedure or surgery
Adjuvant chemotherapy at investigator's discretion
| Study group | Role | What they receive |
|---|---|---|
| Investigational Treatment | Experimental | * Irinotecan 200 mg/m2 IV, day 1
* Capecitabine 1000* mg/m2 po bid day 1-14; repeat every three weeks for two cycles
* For calculated creatinine clearance of 30-50 mL/min or patients > 70 years old, capecitabine starting dose is 825 mg/m2 po bid
* EUS
* Neoadjuvant Chemotherapy
* Preoperative Radiation
* Surgery
* Adjuvant Chemotherapy (at discretion of treating physician) Receives: Drug: Capecitabine; Drug: Irinotecan; Procedure: EUS; Drug: Neoadjuvant Chemotherapy; Procedure: Preoperative Radiation; Procedure: Surgery; Procedure: Adjuvant Chemotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pathological Complete Response (pCR) Rate
- To determine the pathological response rate of preoperative chemotherapy with capecitabine and irinotecan followed by combined modality chemoradiation with capecitabine in patients with locally advanced rectal cancer.
Pathological response was defined in the protocol as the proportion of complete (pCR) and non-complete pathological response (pNCR) among all evaluable patients.
Measured: 36 months
Secondary outcomes (3)
Local and Distant Disease Recurrence Rates
To determine the rates of local and distant disease recurrence after treatment.
Measured: 36 months
Rate of Clinical Response
To determine the rate of clinical response following induction chemotherapy with capecitabine and irinotecan, and also the overall clinical response after the completion of chemoradiation with capecitabine.
Measured: 36 months
Disease-Free Survival
The three year rate of Disease-Free Survival
Measured: 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2005 (estimated)
- Study startMay 2005
- Primary completionMay 2008
- Study completionMay 2008
Why it stopped: Funding withdrawn
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
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gabi Chiorean, MD
- Sponsor type
- University, hospital or other
- Collaborators
- Pfizer, Roche Pharma AG, Walther Cancer Institute
- Responsible party
- Sponsor-investigator, Gabi Chiorean, MD, Hoosier Cancer Research Network
- Investigators
- Elena Gabriela Chiorean, M.D., Study chair, Hoosier Oncology Group, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00216086
- Sponsor's protocol ID
- HOG GI03-53
- Status last verified
- Apr 2016
- First submitted
- 9 Sep 2005
- Last updated
- 6 Jun 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Chiorean EG, Sanghani S, Schiel MA, Yu M, Burns M, Tong Y, Hinkle DT, Coleman N, Robb B, LeBlanc J, Clark R, Bufill J, Curie C, Loehrer PJ, Cardenes H. Phase II and gene expression analysis trial of neoadjuvant capecitabine plus irinotecan followed by capecitabine-based chemoradiotherapy for locally advanced rectal cancer: Hoosier Oncology Group GI03-53. Cancer Chemother Pharmacol. 2012 Jul;70(1):25-32. doi: 10.1007/s00280-012-1883-1. Epub 2012 May 18.
PubMed 22610353
Study at a glance
From the registry record, last updated by the sponsor on 6 Jun 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Trial of Preoperative Capecitabine Plus Irinotecan Followed by Combined Modality Capecitabine and Radiation for Locally Advanced Rectal Cancer: Hoosier Oncology Group GI03-53
- ClinicalTrials.gov ID
- NCT00216086
- Acronym / sponsor ID
- HOG GI03-53
- Conditions
- Rectal Cancer
- Keywords
- Rectal Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Funding withdrawn
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Gabi Chiorean, MDUniversity, hospital or other
- Collaborators
- Pfizer, Roche Pharma AG, Walther Cancer Institute
- Study start
- May 2005
- Primary completion
- May 2008 (actual)
- Study completion
- May 2008 (actual)
- First posted
- 22 Sep 2005 (estimated)
- Results
- Posted 6 Jun 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Preoperative induction chemotherapy has been successfully used in a variety of malignancies and provides several advantages over postoperative therapy. Combination of 5-FU/Leucovorin/CPT-11 has demonstrated significantly better response rate than 5-FU/Leucovorin alone. Replacing 5-FU with oral capecitabine in combination with CPT-11 has emerged as a potentially more effective, safe and convenient treatment option for metastatic colorectal cancer. Capecitabine is also well tolerated in concurrent treatment with radiation. Recent data has shown that preoperative radiation appears to be significantly more effective in increasing resectability rates.
This trial will investigate the activity of capecitabine and CPT-11 combination in the preoperative setting followed by chemoradiation with capecitabine in locally advanced rectal cancer to improve response and decrease local recurrence. We will also study whether TS, TP, DPD and carboxyesterase expressions correlate with the objective response rate with this chemotherapy and chemoradiation regimen.
Detailed description
OUTLINE: This is a multi-center study.
Biopsy per EUS
- Irinotecan 200 mg/m2 IV, day 1
- Capecitabine 1000* mg/m2 PO BID day 1-14 Repeat every three weeks for two cycles* For calculated creatinine clearance of 30-50 mL/min or patients > 70years old, capecitabine starting dose is 825 mg/m2 PO BID
Beginning at week 7 or following recovery from chemotherapy:
- Pelvic XRT 45 Gy/1.8 Gy/fx/qd+5.4 Gy/1.8 Gy/fx/qd for T3+9 Gy/1.8 Gy/fx/qd for T4
- Capecitabine 825* mg/m2 PO BID, 5 days/week, throughout XRT* For calculated creatinine clearance of 30-50 mL/min or patients > 70years old, capecitabine starting dose is 650 mg/m2 PO BID
- Surgery within 8weeks following chemoradiotherapy
- Adjuvant Chemotherapy at investigator's discretion
ECOG performance status 0 or 1
Hematopoietic:·
- ANC count >1,500 mm3·
- Platelets > 100,000/mm3·
- Hemoglobin > 9g/dL
- Prothrombin time (PT)/INR or PTT < 1.25 times upper limit of normal;
Hepatic:·
- Bilirubin <1.5 times upper limit of normal
- Alanine Transaminase (ALT) or Aspartate Transaminase (AST) <2.5 times the upper limit of normal
Renal:·
- Adequate renal function by calculated creatinine clearance > 30 mL/min (by Cockroft and Gault)
Cardiovascular:·
- No congestive heart failure requiring therapy or NYHA class II or greater or active angina or known myocardial infarction within 12 months prior to study
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Investigational Treatment | Experimental | Drug: Capecitabine, Drug: Irinotecan, Procedure: EUS, Drug: Neoadjuvant Chemotherapy, Procedure: Preoperative Radiation, Procedure: Surgery, Procedure: Adjuvant Chemotherapy* Irinotecan 200 mg/m2 IV, day 1 * Capecitabine 1000* mg/m2 po bid day 1-14; repeat every three weeks for two cycles * For calculated creatinine clearance of 30-50 mL/min or patients > 70 years old, capecitabine starting dose is 825 mg/m2 po bid * EUS * Neoadjuvant Chemotherapy * Preoperative Radiation * Surgery * Adjuvant Chemotherapy (at discretion of treating physician) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Histologically confirmed adenocarcinoma of the rectum < 15 cm from the anal verge without evidence of distant metastasis·
- Measurable disease. ·
- Either mobile cancers (with clinical stage T3 or T4 by endorectal ultrasound) or fixed cancer (defined as clinical T4 for this study) on palpation. ·
- Malignant disease may not extend to the anal canal (across the dentate line)
Key exclusion criteria (11 listed)
- No prior chemotherapy or radiation therapy to the pelvis.
- Patients with clinical stage T 1-2, N0 rectal cancer who are candidates for primary resection are not eligible·
- No synchronous colonic cancer unless the synchronous tumor is Tis or T1 and has been completely resected·
- Patients must not be taking warfarin·
- No prior unanticipated severe reaction to fluoropyrimidine therapy, or known sensitivity to 5-Fluorouracil or known DPD deficiency.·
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: XelodaCapecitabine 1000* mg/m2 po bid day 1-14; repeat every three weeks for two cycles *For calculated creatinine clearance of 30-50 mL/min or patients > 70 years old, capecitabine starting dose is 825 mg/m2 po bid | Drug | Investigational Treatment |
| IrinotecanAlso: CamptosarIrinotecan 200 mg/m2 IV, day 1 | Drug | Investigational Treatment |
| EUSbiopsy per EUS | Procedure or surgery | Investigational Treatment |
| Neoadjuvant ChemotherapyAlso: Camptosar, Xeloda* Irinotecan 200 mg/m2 IV, day 1 * Capecitabine 1000 mg/m2 po bid day 1-14; repeat every three weeks for two cycles | Drug | Investigational Treatment |
| Preoperative RadiationPelvic XRT 45 Gy/1.8 GY/fx/qd+5/4 Gy/1.8 Gy/fx/qd for T3+9 Gy/1.8/Gy/fx/qd for T4 | Procedure or surgery | Investigational Treatment |
| SurgerySurgery within 8 weeks following chemoradiotherapy | Procedure or surgery | Investigational Treatment |
| Adjuvant ChemotherapyAdjuvant chemotherapy at investigator's discretion | Procedure or surgery | Investigational Treatment |
Primary outcome
Pathological Complete Response (pCR) Rate
Time frame: 36 months
· To determine the pathological response rate of preoperative chemotherapy with capecitabine and irinotecan followed by combined modality chemoradiation with capecitabine in patients with locally advanced rectal cancer. Pathological response was defined in the protocol as the proportion of complete (pCR) and non-complete pathological response (pNCR) among all evaluable patients.
3 secondary outcomes
Local and Distant Disease Recurrence Rates
Time frame: 36 months
Rate of Clinical Response
Time frame: 36 months
Disease-Free Survival
Time frame: 36 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jun 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 22610353Chiorean EG, Sanghani S, Schiel MA, Yu M, Burns M, Tong Y, Hinkle DT, Coleman N, Robb B, LeBlanc J, Clark R, Bufill J, Curie C, Loehrer PJ, Cardenes H. Phase II and gene expression analysis trial of neoadjuvant capecitabine plus irinotecan followed by capecitabine-based chemoradiotherapy for locally advanced rectal cancer: Hoosier Oncology Group GI03-53. Cancer Chemother Pharmacol. 2012 Jul;70(1):25-32. doi: 10.1007/s00280-012-1883-1. Epub 2012 May 18.
- Hoosier Oncology Group Home PageLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
Elena Gabriela Chiorean, M.D. study chair
Hoosier Oncology Group, LLC
9 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 Capecitabine, Irinotecan and EUS in people with Rectal Cancer, run by Gabi Chiorean, MD at 9 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 4 inclusion and 11 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 6 Jun 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 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 6 Jun 2016). 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?
Pathological Complete Response (pCR) Rate (time frame: 36 months). 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 NCT00216086, 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 6 Jun 2016.