Adenocarcinoma of the Esophagus, Esophageal Cancer, Squamous Cell Carcinoma
Conditions
Keywords
Esophageal cancer, Localized esophageal cancer, Operable esophageal cancer, Loco-regional esophageal cancer, Esophagectomy, Phase 2, Paclitaxel, Tumor, Local, Chemotherapy, radiation therapy, surgery, OncoGel, Squamous cell carcinoma of the esophagus
Brief summary
OncoGel is a new experimental drug delivery system that allows the slow continuous release of paclitaxel (an approved intravenous anticancer drug), from a gel (ReGel) over a long period of time. The gel will disappear in 4 to 6 weeks as it releases the paclitaxel. The protocol is directed towards evaluating the efficacy and safety of paclitaxel delivered as a local, intralesional treatment when used in combination with chemotherapy (cisplatin and 5-FU) and radiation therapy before surgery.
Detailed description
The primary objective of this study is to evaluate the efficacy of OncoGel given in combination with standard chemotherapy (cisplatin and 5-FU) and radiation therapy in patients with previously untreated, resectable, local or local-regional adenosarcoma or squamous cell carcinoma. All patients will receive IV cisplatin on Day 1 and Day 29 and IV 5-FU given continuously for 96 hours starting on Day 1 and Day 29. All patients will also receive out-patient radiation therapy for 28 treatments once per day for 5 1/2 weeks starting on Day 1. Patients randomized to the OncoGel treatment group will have the OncoGel dose injected into their esophageal tumors during an endoscopic procedure just before starting systemic chemotherapy and radiation therapy. All patients will have CT scans for tumor measurements before starting chemotherapy and 12 weeks later after completion of the radiation therapy and both cycles of chemotherapy. During the chemotherapy and radiation therapy, physical exams, vital signs, routine blood tests will be performed. Patients will also be asked about their quality of life and ability to swallow. In-patient surgery will be scheduled 4 to 6 weeks after completion of chemotherapy and radiation therapy. The resected esophagus and lymph nodes will be evaluated for the presence of residual tumor. Patients will be followed at months 4, 5, 6, and then every 3 Months thereafter for survival and esophageal cancer status and treatment until the last patient enrolled has completed their Month 12 visit.
Interventions
DRUGOncoGel (Paclitaxel gel)
6.3 mg/mL tumor volume, injected into the esophagus during endoscopy, once, before starting chemoradiotherapy
DRUGcisplatin
75 mg/m2 IV (in the vein) once on Day 1 and Day 29
DRUG5-FU
1000 mg/m2/day, IV (in the vein) for 4 days (96 hours) for two cycles starting on Day 1 and Day 29
RADIATIONradiation therapy
50.4 Gy, given in 28 treatments, once per day for 5 1/2 weeks
PROCEDUREesophageal resection
Removal of esophagus after completion of chemotherapy and radiation therapy
Sponsors
Boston Scientific Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Histologically or cytologically confirmed squamous cell carcinoma or adenocarcinoma of the esophagus. Stage T2-T3, N any, M0 (no evidence of disseminated cancer except regional involvement which may be designated as M1a). No evidence of metastatic disease 2. Medically able to tolerate major abdominal and/or thoracic surgery 3. Able to undergo EUS procedure and pass EUS probe through esophageal lumen 4. Able to receive concurrent systemic chemotherapy (cisplatin and 5-FU) and RT 5. Clinical management plan includes esophagectomy after completion of two courses of chemoradiation therapy 6. Karnofsky Performance Status of ≥ 60 7. Minimum life expectancy of 4 months 8. Hematologic function * Absolute neutrophil count (ANC) ≥ 1500/mm3 * Platelet count ≥ 100,000/mm3 * Hemoglobin ≥ 9 g/dL 9. Hepatic function: * Total bilirubin \< 1.5 X upper limit of normal (ULN) * AST and ALT \< 3 X ULN * Albumin ≥ 3.0 g/dL or ≥ 2.0 g/dL if the lower level is considered by the investigator to be due to nutritional depletion 10. Serum creatinine \< 1.5 mg/dL and/or creatinine clearance ≥ 65 mL/min 11. ≥ 18 years old 12. If female, must be non-pregnant, nonlactating, of non-childbearing potential, or using adequate birth control 13. Capable of understanding and agreeing to fulfill the requirements of the protocol 14. Sign the IRB/EC approved consent form
Exclusion criteria
1. History of anaphylaxis to planned CT contrast agent 2. Prior esophageal stent insertion, laser, or photodynamic therapy 3. Prior chest RT or major esophageal surgery 4. Any prior receipt of cytotoxic chemotherapeutic agents 5. Prior receipt of other cancer treatments (ie, Chelation therapy), vaccines, or biological response modifiers/growth factors (ie, GM-CSF, IL-2) within the past 4 weeks. 6. Prior malignancy unless disease free for ≥ 3 years. Note: basal cell/squamous carcinoma of the skin, in situ cervical or breast carcinoma, or superficial transitional cell bladder carcinoma will be allowed. Subjects with a history of low risk prostatic carcinoma (ie, clinical stage 1 or 2a, Gleason score \< or = 6 and PSA \<10 ng/mL at diagnosis) will be allowed 7. Significant currently active systemic diseases including uncontrolled diabetes, severe heart disease (New York Heart Association Class III or IV), uncontrolled hypertension, myocardial infarction within 3 months, severe bronchial obstruction, uncontrolled seizure disorder, or peripheral neuropathy greater than CTCAE grade 1 8. Allergies to any of the active or inactive components of OncoGel (ie, allergies to degradable PLGA \[poly(lactide-co-glycolide) sutures\]) 9. Receipt of an investigational drug or device within 30 days prior to signing informed consent 10. Any medical condition or other circumstance that, in the Investigator's opinion, would prevent completion of the study, interfere with analysis of the study results, or potentially adversely affect subject safety 11. Known esophageal varices
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Tumor Response at the Primary Tumor Site Based on Measurement of Primary Tumor Volume (Excluding Involved Lymph Nodes) by Spiral CT | Screening and Week 12 | Per the Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and by Spiral CT assessment: Complete Response (CR) is the disappearance of all target lesions; Partial Response (PR) is a \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR |
Countries
Czechia, India, Poland, United States
Participant flow
Recruitment details
Patients were enrolled from 21 Jan 2008 through 05 Nov 2010 at 20 centers in 5 countries (United States, India, Poland, Czech Republic and Belgium).
Participants by arm
| Arm | Count |
|---|---|
| Group 1 OncoGel, radiation therapy and systemic chemotherapy (cisplatin plus 5-FU) prior to surgical resection. | 72 |
| Group 2 Radiation therapy and systemic chemotherapy (cisplatin plus 5-FU) prior to surgical resection. | 65 |
| Total | 137 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 10 | 8 |
Baseline characteristics
| Characteristic | Group 1 | Group 2 | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 17 Participants | 17 Participants | 34 Participants |
| Age, Categorical Between 18 and 65 years | 55 Participants | 48 Participants | 103 Participants |
| Age, Continuous | 58.4 years STANDARD_DEVIATION 7.2 | 57.6 years STANDARD_DEVIATION 10.9 | 58.0 years STANDARD_DEVIATION 9.1 |
| Region of Enrollment Belgium | 0 participants | 1 participants | 1 participants |
| Region of Enrollment Czech Republic | 14 participants | 11 participants | 25 participants |
| Region of Enrollment India | 37 participants | 35 participants | 72 participants |
| Region of Enrollment Poland | 8 participants | 9 participants | 17 participants |
| Region of Enrollment United States | 13 participants | 9 participants | 22 participants |
| Sex: Female, Male Female | 19 Participants | 21 Participants | 40 Participants |
| Sex: Female, Male Male | 53 Participants | 44 Participants | 97 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 67 / 72 | 55 / 65 |
| serious Total, serious adverse events | 30 / 72 | 20 / 65 |
Outcome results
Primary
Overall Tumor Response at the Primary Tumor Site Based on Measurement of Primary Tumor Volume (Excluding Involved Lymph Nodes) by Spiral CT
Per the Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and by Spiral CT assessment: Complete Response (CR) is the disappearance of all target lesions; Partial Response (PR) is a \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
Time frame: Screening and Week 12
Population: Subjects who received at least one treatment with OncoGel, systemic chemotherapy or external beam radiation therapy were included for analysis of efficacy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 | Overall Tumor Response at the Primary Tumor Site Based on Measurement of Primary Tumor Volume (Excluding Involved Lymph Nodes) by Spiral CT | 12.5 percentage of patients |
| Group 2 | Overall Tumor Response at the Primary Tumor Site Based on Measurement of Primary Tumor Volume (Excluding Involved Lymph Nodes) by Spiral CT | 20.0 percentage of patients |