Rectal Neoplasms
Conditions
Keywords
rectal neoplasms, aged, chemoradiotherapy, clinical trials, phase I, capecitabine
Brief summary
This phase I study is designed to determine the maximum tolerant dose of capecitabine when used in preoperative concurrent chemo-radiation for locally advanced rectal patients over 75 years old.
Detailed description
It is proved that preoperative concurrent chemo-radiotherapy can improve both local control and overall survival in stage II/III rectal cancer patients. But elderly patients, especially patients over 75 years were hardly involved in related clinical trials considered of their fragility. Several retrospective study showed that old rectal cancer patients would also benefit from concurrent chemo-radiation, with acceptable toxicity. Several new drug, such as capecitabine, also seem to be safety for elderly cancer patients. But few prospective study has been carried out. The investigators designed this phase I study, to explore the maximum tolerant dose of capecitabine in preoperative concurrent chemoradiation for elderly stage II/III rectal cancer patients, as well as to evaluate safety.
Interventions
DRUGcapecitabine
oral pills, 1000mg/m2/d, split in two times, d1-14, d22-35 combined with concurrent pelvic radiation
DRUGCapecitabine
oral pills, 1200mg/m2/d, split in two times, d1-14, d22-35 combined with concurrent pelvic radiation
Sponsors
Chinese Academy of Medical Sciences
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
75 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* rectal adenocarcinoma, clinical stage II/III(T3-4 or N+, AJCC 7th). * KPS status no less than 70; Charlson comorbidity no more than 3. * life expectancy more than 6 months. * hemoglobin \>= 100g/L, white blood cell \>= 3.5\*10E9/L, neutrophil \>= 1.5\*10E9/L, platelet \>= 100\*10E9/L.Creatin normal, Total bilirubin normal, AST and AST normal, AKP normal. * do not have allergy history to thymidine phosphorylase. * do not receive surgery ( except palliative colostomy) or chemotherapy or other anti-cancer treatment * no previously pelvic irradiation history * informed consent signed
Exclusion criteria
* other cancer history, except curable non-melanoma skin cancer or cervix in-situ carcinoma * previous pelvic irradiation history * receiving surgery (except palliative colostomy), chemotherapy or other anti-cancer treatment * allergy history to thymidine phosphorylase * active infection existed * severe complication, such as acute myocardial infarction in 6 months, uncontrolled diabetes ( Plasma glucose concentrations in any time of a day≥11.1mmol/L）, severe cardiac arrhythmia， etc. * anticipate other clinical trials in four weeks before enrollment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Experienced Dose Limited Toxicity | up to 7 weeks from start of the treatment | Dose related toxicity is defined as follows:1. luecopenia \> grade 2; granular cell decrease \> grade 2; anemia \> grade 1; platelet \> grade 1;SGPT/SGOT elevation \> grade 1; ALP \> grade 1; GGT \> grade 1; Tbil \> grade 1;renal function damag \> grade 2;Non-gradular cell decreased fever \> grade 1;nausea/vomiting \> grade 1; fatigue \> grade 2; weight loss \> grade 2;gastritis \> grade 2; dairrea \> grade 2; abdominal pain \> grade 2; upper gastrointestinal bleeding \> grade 1;other toxic reaction \> grade 2;KPS \< 50 during the treatment |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 1000mg capecitabine 1000mg/m2/d d1-14, d22-25 combined with concurrent radiotherapy will be given to enrolled patients.
capecitabine: oral pills, 1000mg/m2/d, split in two times, d1-14, d22-35 combined with concurrent pelvic radiation | 3 |
| 1200mg capecitabine 1200mg/m2/d d1-14, d22-35 combined with concurrent radiotherapy will be given to enrolled patients.
Capecitabine: oral pills, 1200mg/m2/d, split in two times, d1-14, d22-35 combined with concurrent pelvic radiation | 6 |
| 1350mg capecitabine 1300mg/m2/d d1-14, d22-35 combined with concurrent radiotherapy will be given to enrolled patients.
Capecitabine: oral pills, 1350mg/m2/d, split in two times, d1-14, d22-35 combined with concurrent pelvic radiation | 6 |
| 1500mg capecitabine 1500mg/m2/d d1-14, d22-35 combined with concurrent radiotherapy will be given to enrolled patients.
Capecitabine: oral pills, 1500mg/m2/d, split in two times, d1-14, d22-35 combined with concurrent pelvic radiation | 3 |
| 1650mg capecitabine 1650mg/m2/d d1-14, d22-35 combined with concurrent radiotherapy will be given to enrolled patients.
Capecitabine: oral pills, 1650mg/m2/d, split in two times, d1-14, d22-35 combined with concurrent pelvic radiation | 6 |
| Total | 24 |
Baseline characteristics
| Characteristic | 1200mg | 1350mg | 1500mg | 1000mg | 1650mg | Total |
|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 6 Participants | 6 Participants | 3 Participants | 3 Participants | 6 Participants | 24 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 77 years | 78 years | 76 years | 77 years | 78 years | 78 years |
| Region of Enrollment China | 6 participants | 6 participants | 3 participants | 3 participants | 6 participants | 24 participants |
| Sex: Female, Male Female | 3 Participants | 2 Participants | 1 Participants | 1 Participants | 4 Participants | 11 Participants |
| Sex: Female, Male Male | 3 Participants | 4 Participants | 2 Participants | 2 Participants | 2 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 3 | 6 / 6 | 6 / 6 | 3 / 3 | 6 / 6 |
| serious Total, serious adverse events | 0 / 3 | 1 / 6 | 1 / 6 | 0 / 3 | 1 / 6 |
Outcome results
Primary
Number of Participants Experienced Dose Limited Toxicity
Dose related toxicity is defined as follows:1. luecopenia \> grade 2; granular cell decrease \> grade 2; anemia \> grade 1; platelet \> grade 1;SGPT/SGOT elevation \> grade 1; ALP \> grade 1; GGT \> grade 1; Tbil \> grade 1;renal function damag \> grade 2;Non-gradular cell decreased fever \> grade 1;nausea/vomiting \> grade 1; fatigue \> grade 2; weight loss \> grade 2;gastritis \> grade 2; dairrea \> grade 2; abdominal pain \> grade 2; upper gastrointestinal bleeding \> grade 1;other toxic reaction \> grade 2;KPS \< 50 during the treatment
Time frame: up to 7 weeks from start of the treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1000mg | Number of Participants Experienced Dose Limited Toxicity | 0 participants |
| 1200mg | Number of Participants Experienced Dose Limited Toxicity | 1 participants |
| 1350mg | Number of Participants Experienced Dose Limited Toxicity | 1 participants |
| 1500mg | Number of Participants Experienced Dose Limited Toxicity | 0 participants |
| 1650mg | Number of Participants Experienced Dose Limited Toxicity | 1 participants |