Esophageal Cancer
Conditions
Brief summary
The aim of this trial is to find the maximum tolerable dose of radiation that can be delivered combined with chemotherapy (DDP & Paclitaxel) in patients with inoperable or medically unresectable esophageal cancer.
Detailed description
The RTOG 8501 has established concurrent radiochemotherapy as the standard of care for cancer of the esophagus.However, locoregional remain problematic, with 25% of patients having persistence and 20% relapse of locoregional disease following the combined modality approach. New regimen is urgently needed for improving localregional control and survival.
Interventions
RADIATIONradiochemotherapy 1
concurrent radiochemotherapy: radiotherapy dose level 1: 50 Gy at 2 Gy/Fx/d, then 7.2 Gy at 1.2 Gy/Fx/bid; concurrent chemotherapy: carboplatin, area under the curve (AUC) 1.5-2, weekly; paclitaxel, 45-50 mg/m2, weekly
RADIATIONradiochemotherapy 2
concurrent radiochemotherapy: radiotherapy dose level 1: 50 Gy at 2 Gy/Fx/d, then 14.4 Gy at 1.2 Gy/Fx/bid; concurrent chemotherapy: carboplatin, area under the curve (AUC) 1.5-2,weekly; paclitaxel, 45-50 mg/m2, weekly
RADIATIONradiochemotherapy 3
concurrent radiochemotherapy: radiotherapy dose level 1: 50 Gy at 2 Gy/Fx/d, then 21.6 Gy at 1.2 Gy/Fx/bid; concurrent chemotherapy: carboplatin, area under the curve (AUC) 1.5-2,weekly; paclitaxel, 45-50 mg/m2, weekly
RADIATIONradiochemotherapy 4
concurrent radiochemotherapy: radiotherapy dose level 1: 50 Gy at 2 Gy/Fx/d, then 28.8 Gy at 1.2 Gy/Fx/bid; concurrent chemotherapy: carboplatin, area under the curve (AUC) 1.5-2,weekly; paclitaxel, 45-50 mg/m2, weekly
RADIATIONradiochemotherapy 5
concurrent radiochemotherapy: radiotherapy dose level 1: 50 Gy at 2 Gy/Fx/d, then 36 Gy at 1.2 Gy/Fx/bid; concurrent chemotherapy: carboplatin, area under the curve (AUC) 1.5-2,weekly; paclitaxel, 45-50 mg/m2, weekly;
RADIATIONradiochemotherapy 6
concurrent radiochemotherapy: radiotherapy dose level 1: 50 Gy at 2 Gy/Fx/d, then 43.2 Gy at 1.2 Gy/Fx/bid concurrent chemotherapy: carboplatin, area under the curve (AUC) 1.5-2,weekly; paclitaxel, 45-50 mg/m2, weekly
Sponsors
Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Masking description
open label
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Histologically confirmed primary squamous cell carcinoma of the esophagus 2. Age 1 8-75. 3. Patients must be deemed unresectable disease or patient is not deemed operable due to medical reasons. 4. Patients with distant metastasis and life expectancy \>/= 3 months are eligible. 5. Zubrod performance status 0 to 2 6. No prior radiation to the thorax that would overlap with the current treatment field. 7. Patients with nodal involvement are eligible 8. Adequate bone marrow, renal and hepatic functions as assessed by the following: Hemoglobin \>/= 10.0 g/dl, Platelet count \>/= 1 00,000/mm\^3,absolute granulocyte count (AGC) ≥2 × 10\^9 cells/L,bilirubin and Aspartate transaminase ≤1.5 ×upper limit of normal (ULN), Creatinine \</=1 .5 times ULN. 9. A signed informed consent must be obtained prior to therapy. 1 0. Induction chemotherapy is allowed.
Exclusion criteria
1. The presence of a fistula. 2. Prior radiotherapy that would overlap the radiation fields. 3. gastroesophageal junction cancer. 4. Uncontrolled concurrent illness including, but not limited to: Chronic Obstructive Pulmonary Disease(COPD) exacerbation or other respiratory illness, serious uncontrolled infection, symptomatic congestive heart failure (CHF),unstable angina pectoris, uncontrolled hypertension,or psychiatric illness/social situations that would limit compliance with the study requirements. 5. Known hypersensitivity to paclitaxel. 6. Any other condition or circumstance that would, in the opinion of the Investigator, make the patient unsuitable for participation in the study. 7. Acquired Immune Deficiency Syndrome. 8. Conditions precluding medical follow-up and protocol compliance
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Dose Limiting Toxicities (DLTs) Occurring in Participants | 15 months | The DLTs were defined as grade \>/=4 esophatitis, any other grade \>/=3 nonhematological toxicity (except nausea and vomiting), or grade \>/=4 hematological toxicity lasting more than 7 days, which are possibly, probably, or definitely associated with protocol treatment occurring during and after completion of the HFRT boost treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Local Failure | 15 months | Local failure will be assessed radiographically using endoscopy with biopsy, CT scan, and a positron emission computed tomography-CT scan. which was defined as persistence /recurrence of the tumor in the radiation therapy field. |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Radiochemotherapy 1 3 Patients will be treated with radiation therapy 57.2 Gy.
radiochemotherapy 1: concurrent radiochemotherapy: radiotherapy dose level 1: 50 Gy at 2 Gy/Fx/d, then 7.2 Gy at 1.2 Gy/Fx/bid; concurrent chemotherapy: carboplatin, area under the curve (AUC) 1.5-2, weekly; paclitaxel, 45-50 mg/m2, weekly | 3 |
| Radiochemotherapy 2 3 Patients will be treated with radiation therapy 64.4 Gy.
radiochemotherapy 2: concurrent radiochemotherapy: radiotherapy dose level 1: 50 Gy at 2 Gy/Fx/d, then 14.4 Gy at 1.2 Gy/Fx/bid; concurrent chemotherapy: carboplatin, area under the curve (AUC) 1.5-2,weekly; paclitaxel, 45-50 mg/m2, weekly | 3 |
| Radiochemotherapy 3 3 Patients will be treated with radiation therapy 71.6 Gy.
radiochemotherapy 3: concurrent radiochemotherapy: radiotherapy dose level 1: 50 Gy at 2 Gy/Fx/d, then 21.6 Gy at 1.2 Gy/Fx/bid; concurrent chemotherapy: carboplatin, area under the curve (AUC) 1.5-2,weekly; paclitaxel, 45-50 mg/m2, weekly | 3 |
| Radiochemotherapy 4 6 Patients will be treated with radiation therapy 78.8 Gy.
radiochemotherapy 4: concurrent radiochemotherapy: radiotherapy dose level 1: 50 Gy at 2 Gy/Fx/d, then 28.8 Gy at 1.2 Gy/Fx/bid; concurrent chemotherapy: carboplatin, area under the curve (AUC) 1.5-2,weekly; paclitaxel, 45-50 mg/m2, weekly | 6 |
| Radiochemotherapy 5 13 Patients will be treated with radiation therapy 86 Gy.
radiochemotherapy 5: concurrent radiochemotherapy: radiotherapy dose level 1: 50 Gy at 2 Gy/Fx/d, then 36 Gy at 1.2 Gy/Fx/bid; concurrent chemotherapy: carboplatin, area under the curve (AUC) 1.5-2,weekly; paclitaxel, 45-50 mg/m2, weekly; | 13 |
| Radiochemotherapy 6 3 Patients will be treated with radiation therapy 93.2 Gy.
radiochemotherapy 6: concurrent radiochemotherapy: radiotherapy dose level 1: 50 Gy at 2 Gy/Fx/d, then 43.2 Gy at 1.2 Gy/Fx/bid concurrent chemotherapy: carboplatin, area under the curve (AUC) 1.5-2,weekly; paclitaxel, 45-50 mg/m2, weekly | 3 |
| Total | 31 |
Baseline characteristics
| Characteristic | Radiochemotherapy 1 | Radiochemotherapy 2 | Radiochemotherapy 3 | Radiochemotherapy 4 | Radiochemotherapy 5 | Radiochemotherapy 6 | Total |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 1 Participants | 1 Participants | 3 Participants | 5 Participants | 2 Participants | 14 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 2 Participants | 2 Participants | 3 Participants | 8 Participants | 1 Participants | 17 Participants |
| Eastern Cooperative Oncology Group, ECOG performance status 0-1 | 3 Participants | 2 Participants | 3 Participants | 5 Participants | 12 Participants | 3 Participants | 28 Participants |
| Race and Ethnicity Not Collected | — | — | — | — | — | — | 0 Participants |
| Region of Enrollment China | 3 participants | 3 participants | 3 participants | 6 participants | 13 participants | 3 participants | 31 participants |
| Sex: Female, Male Female | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 5 Participants | 0 Participants | 8 Participants |
| Sex: Female, Male Male | 2 Participants | 3 Participants | 2 Participants | 5 Participants | 8 Participants | 3 Participants | 23 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 | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 6 | 0 / 13 | 1 / 3 |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 3 / 3 | 5 / 6 | 11 / 13 | 1 / 3 |
| serious Total, serious adverse events | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 6 | 0 / 13 | 2 / 3 |
Outcome results
Primary
Number of Dose Limiting Toxicities (DLTs) Occurring in Participants
The DLTs were defined as grade \>/=4 esophatitis, any other grade \>/=3 nonhematological toxicity (except nausea and vomiting), or grade \>/=4 hematological toxicity lasting more than 7 days, which are possibly, probably, or definitely associated with protocol treatment occurring during and after completion of the HFRT boost treatment.
Time frame: 15 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1: Radiochemotherapy 1 | Number of Dose Limiting Toxicities (DLTs) Occurring in Participants | 0 dose limiting toxicity |
| Arm 2: Radiochemotherapy 2 | Number of Dose Limiting Toxicities (DLTs) Occurring in Participants | 0 dose limiting toxicity |
| Arm 3：Radiochemotherapy 3 | Number of Dose Limiting Toxicities (DLTs) Occurring in Participants | 0 dose limiting toxicity |
| Arm 4: Radiochemotherapy 4 | Number of Dose Limiting Toxicities (DLTs) Occurring in Participants | 1 dose limiting toxicity |
| Arm 5: Radiochemotherapy 5 | Number of Dose Limiting Toxicities (DLTs) Occurring in Participants | 0 dose limiting toxicity |
| Arm 6: Radiochemotherapy 6 | Number of Dose Limiting Toxicities (DLTs) Occurring in Participants | 2 dose limiting toxicity |
Secondary
Local Failure
Local failure will be assessed radiographically using endoscopy with biopsy, CT scan, and a positron emission computed tomography-CT scan. which was defined as persistence /recurrence of the tumor in the radiation therapy field.
Time frame: 15 months
Population: the patients who completed the protocol treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1: Radiochemotherapy 1 | Local Failure | 0 Participants |
| Arm 2: Radiochemotherapy 2 | Local Failure | 1 Participants |
| Arm 3：Radiochemotherapy 3 | Local Failure | 1 Participants |
| Arm 4: Radiochemotherapy 4 | Local Failure | 0 Participants |
| Arm 5: Radiochemotherapy 5 | Local Failure | 0 Participants |
| Arm 6: Radiochemotherapy 6 | Local Failure | 0 Participants |