Rectal Neoplasms
Conditions
Keywords
rectal neoplasms, aged, radiotherapy, drug therapy, dose-escalation, capecitabine
Brief summary
The purpose of this study is to seek the proper dose of capecitabine in post-operative concurrent chemotherapy for stage II/III elderly rectal cancer patients receiving radical surgery, and evaluate the toleration of this modality in such patients.
Detailed description
For those younger locally advanced (stage II/III) rectal cancer patients (usually means patients less than 70), it is suggested that after radical surgery, patients should receive concurrent chemo-radiation. Capecitabine is a widely used chemotherapy medicine under such condition. Based on experience, the investigators think this modality can also be tolerated by patients over 70, and will increase local control rate as which has been proved in younger ones. As the first step to test this hypothesis, we designed this phase I study to seek the proper dose of capecitabine, a widely used oral chemotherapy medicine, in postoperative concurrent chemo-radiation for stage II/III rectal cancer patients over 70, and to evaluate the safety of this modality in this group of patients.
Interventions
DRUGCapecitabine
oral pills, 1000mg/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
71 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* rectal adenocarcinoma, pathological stage II/III(T3-4 or N+, UICC 2002), radical surgery received. * interval between surgery and enrollment no less than two week and no more than 3 months. * KPS status no less than 70; life expectancy no less than 6 months. * without life-threatening complications, such as severe hypertension, coronary heart disease, cerebral vascular disease, uncontrolled diabetes, etc. * without severe drug allergy history. * hemoglobin \>= 100g/L, white blood cell \>= 3.5\*10E9/L, neutrophil \>= 1.5\*10E9/L, platelet \>= 100\*10E9/L. * Creatin \<= 1.5\* ULN(upper limit of normal), Total bilirubin \<= 2.5 ULN, AST and AST \<= 2.5\* ULN, AKP \<= 2.5\*ULN * do not receive chemotherapy before six months from enrollment. * no previously pelvic irradiation history * informed consent signed
Exclusion criteria
* other cancer history, except curable non-melanoma skin cancer or cervix in-situ carcinoma * allergy history to thymidine phosphorylase * previous pelvic irradiation history * receiving adjuvant chemotherapy in six months before enrollment * 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. * life expectancy less than 6 months * estimated cannot finish treatment * attend other clinical trials in four weeks before enrollment * receive other anti-cancer treatment currently * other conditions which regarded illegal by censors with full reasons. for example, some conditions may conflict from the protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose Related Toxicity | up to 9 weeks | dose related toxicity is defined as follows:1. WBC damage \>= grade 3; granular cell decrease \>= grade 3; hemoglobin \>= grade 2; platelet \>= grade 2;SGPT/SGOT elevation \>= grade 2; ALP \>= grade 2; GGT \>= grade 2; Tbil \>= grade 2;renal function damage: BUN/Cr elevation \>= grade 2;Non-gradular cell decreased fever \>= grade 2;nausea/vomiting \>= grade 2; fatigue \>= grade 3; weight loss \>= grade 3;gastritis \>= grade 3; dairrea \>= grade 3; abdominal pain \>= grade 3; pancreatitis \>= grade 2; upper gastrointestinal bleeding \>= grade 2;other toxic reaction \>= grade 3;KPS \< 50 during the treatment |
Countries
China
Participant flow
Recruitment details
Between October 2010 and November 2013, 18 patients were enrolled in a hospital.
Participants by arm
| Arm | Count |
|---|---|
| 1000mg capecitabine 500mg/m2 twice daily. 6 patients enrolled | 6 |
| 1200mg capecitabine 600mg/m2 twice daily. 3 patients enrolled | 3 |
| 1400mg capecitabine 700mg/m2 twice daily. 3 patients enrolled | 3 |
| 1500mg capecitabine 750mg/m2 twice daily. 6 patients enrolled | 6 |
| Total | 18 |
Baseline characteristics
| Characteristic | 1000mg | 1200mg | 1400mg | 1500mg | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 6 Participants | 3 Participants | 3 Participants | 6 Participants | 18 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 75.5 years | 73.7 years | 75.7 years | 73.5 years | 74.5 years |
| Sex: Female, Male Female | 1 Participants | 0 Participants | 0 Participants | 4 Participants | 5 Participants |
| Sex: Female, Male Male | 5 Participants | 3 Participants | 3 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 |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 6 | 2 / 3 | 3 / 3 | 5 / 6 |
| serious Total, serious adverse events | 1 / 6 | 0 / 3 | 0 / 3 | 2 / 6 |
Outcome results
Primary
Dose Related Toxicity
dose related toxicity is defined as follows:1. WBC damage \>= grade 3; granular cell decrease \>= grade 3; hemoglobin \>= grade 2; platelet \>= grade 2;SGPT/SGOT elevation \>= grade 2; ALP \>= grade 2; GGT \>= grade 2; Tbil \>= grade 2;renal function damage: BUN/Cr elevation \>= grade 2;Non-gradular cell decreased fever \>= grade 2;nausea/vomiting \>= grade 2; fatigue \>= grade 3; weight loss \>= grade 3;gastritis \>= grade 3; dairrea \>= grade 3; abdominal pain \>= grade 3; pancreatitis \>= grade 2; upper gastrointestinal bleeding \>= grade 2;other toxic reaction \>= grade 3;KPS \< 50 during the treatment
Time frame: up to 9 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1000mg | Dose Related Toxicity | 1 event |
| 1200mg | Dose Related Toxicity | 0 event |
| 1400mg | Dose Related Toxicity | 0 event |
| 1500mg | Dose Related Toxicity | 3 event |