Rectal Cancer
Conditions
Keywords
Rectal Cancer
Brief 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. 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
Interventions
DRUGCapecitabine
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
DRUGIrinotecan
Irinotecan 200 mg/m2 IV, day 1
PROCEDUREEUS
biopsy per EUS
DRUGNeoadjuvant Chemotherapy
* Irinotecan 200 mg/m2 IV, day 1 * Capecitabine 1000 mg/m2 po bid day 1-14; repeat every three weeks for two cycles
PROCEDUREPreoperative Radiation
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
PROCEDURESurgery
Surgery within 8 weeks following chemoradiotherapy
PROCEDUREAdjuvant Chemotherapy
Adjuvant chemotherapy at investigator's discretion
Sponsors
Pfizer
Roche Pharma AG
Walther Cancer Institute
Gabi Chiorean, MD
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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)
Exclusion criteria
* 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· * 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pathological Complete Response (pCR) Rate | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Local and Distant Disease Recurrence Rates | 36 months | To determine the rates of local and distant disease recurrence after treatment. |
| Rate of Clinical Response | 36 months | 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. |
| Disease-Free Survival | 36 months | The three year rate of Disease-Free Survival |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Single Group Assignment 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
Capecitabine: 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
Irinotecan: Irinotecan 200 mg/m2 IV, day 1
EUS: biopsy per EUS
Neoadjuvant Chemotherapy: Irinotecan 200 mg/m2 IV, day 1 Capecitabine 1000 mg/m2 po bid day 1-14; repeat every three weeks for two cycles
Preoperative Radiation: 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
Surgery: Surgery within 8 weeks following chemoradiotherapy
Adjuvant Chemotherapy: Adjuvant chemotherapy at investigator's discretion | 22 |
| Total | 22 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Diagnosis of Metastatic Disease | 1 |
| Overall Study | Protocol Violation | 1 |
| Overall Study | Social Reasons | 2 |
Baseline characteristics
| Characteristic | Single Group Assignment |
|---|---|
| Age, Continuous | 54 years |
| Eastern Cooperative Oncology Group (ECOG) performance status 0 | 7 participants |
| Eastern Cooperative Oncology Group (ECOG) performance status 1 | 15 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 17 Participants |
| Region of Enrollment United States | 22 participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 11 Participants |
| Tumor Node Metastatis (TNM) Stage T2 | 1 participants |
| Tumor Node Metastatis (TNM) Stage T3 | 19 participants |
| Tumor Node Metastatis (TNM) Stage T4 | 2 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 21 / 22 |
| serious Total, serious adverse events | 6 / 22 |
Outcome results
Primary
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.
Time frame: 36 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Single Group Assignment | Pathological Complete Response (pCR) Rate | pCR | 33 percentage of patients |
| Single Group Assignment | Pathological Complete Response (pCR) Rate | pNCR | 56 percentage of patients |
Secondary
Disease-Free Survival
The three year rate of Disease-Free Survival
Time frame: 36 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Single Group Assignment | Disease-Free Survival | 75.5 percentage |
Secondary
Local and Distant Disease Recurrence Rates
To determine the rates of local and distant disease recurrence after treatment.
Time frame: 36 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Single Group Assignment | Local and Distant Disease Recurrence Rates | metastatic disease recurrence | 22 percentage of particpants |
| Single Group Assignment | Local and Distant Disease Recurrence Rates | locally recurrence | 0 percentage of particpants |
Secondary
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.
Time frame: 36 months
Population: Data for this secondary objective was not captured or analyzed due to the withdrawal of funding and subsequent termination of the study.