Purpose: To evaluate the feasibility and efficacy of a combination of preoperative chemoradiation of Paclitaxel 50mg/m2 and Carboplatin AUC 2 given intravenously on day 1, 8,15, 22 and 29 in combination with 45 Gy (fractions of 1.8Gy) for locally…
ID
Source
Brief title
Condition
- Malignant and unspecified neoplasms gastrointestinal NEC
- Gastrointestinal neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is the possible delay in performing a curative resection
due to increased toxicity of more than 10% with a stopping point at a delay in
six patients.
Secondary outcome
Secondary endpoints are :
- efficacy
- occurence of downstaging and changes in pathology
Background summary
Rationale: The incidence of gastric cancer has been declining steadily since
the 1930s, but it remains a major cause of cancer death in the Western world.
The high mortality rate reflects the prevalence of advanced disease at
presentation. The five-year survival rate for patients with completely resected
early stage gastric cancer is approximately 75%, while it is 30% or less for
patients who have extensive lymph node involvement. However, nearly 70-80% of
the resected gastric carcinoma specimens have regional lymph nodes and over 80%
of patients who die from gastric cancer experience a local recurrence at some
time in their disease. These sobering results have gathered efforts to improve
treatment results for these patients using adjuvant (postoperative) or
neoadjuvant (preoperative) radiation therapy (RT) and/or chemotherapy. The
rational for chemoradiation is the risk for locoregional recurrence and distant
metastases. Radiation with surgery can improve locoregional control while
systematic chemotherapy can eliminate microscopic distant metastases. As
limited data that exist, fail to show a survival benefit from the addition of
postoperative RT alone in patients with resected gastric cancer, almost all
postoperative RT trials have included concurrent chemotherapy to improve the
efficacy of RT ("radiation sensitization"). Over time adjuvant chemoradiation
is considered as standard of care after curative surgery for adenocarcinoma of
stomach cancer in many countries. Preoperative chemoradiotherapy in locally
advanced gastric cancer results in significant down staging of the tumor with
improved rate of curative resections.
Chemotherapy may also function as a radiosensitiser, improving the effect of
radiation by double-stranded DNA breaks and inhibition of DNA repair by
blocking the cell cycle at the G2/M phase. Recent studies have shown activity
of Paclitaxel in conjunction with radiation in gastric cancer.
Study objective
Purpose: To evaluate the feasibility and efficacy of a combination of
preoperative chemoradiation of Paclitaxel 50mg/m2 and Carboplatin AUC 2 given
intravenously on day 1, 8,15, 22 and 29 in combination with 45 Gy (fractions of
1.8Gy) for locally advanced adenocarcinoma of the stomach.
Study design
Type: Interventional
Design: Non-Randomized, Open Label, Uncontrolled, Multi Group Assignment study
Intervention
Intervention is the use of chemoradiotherapy as an adjunct to the standard
surgical resectioen. As adjuvant chemoradiation has some disadvantages such as
an improved possibilty to abandon chemoradiotherapy because of postoperative
complications leading to a to long postoperative course. Therefore neoadjuvant
application has several advantages such as good performance status, better
response measuring and more curative resections (R0).
Study burden and risks
The burden or risk associated with this study is considered to be low and will
be subject of this study.
Postbus 30.001
9700 RB Groningen
Nederland
Postbus 30.001
9700 RB Groningen
Nederland
Listed location countries
Age
Inclusion criteria
- Histologically proven and documented adenocarcinoma of the stomach
- Surgical resectable gastric cancer stage IB-IVA: T1N1; T2-4, N0-1, M0 ( see appendix), as determined by Endoscopic Ultra Sound (EUS), Computed Tomography (CT).
- Age >= 18 and <= 75
- Ambulatory performance status (WHO scale 0 - 2; see appendix)
- No prior chemotherapy
- No prior radiotherapy
- If the tumor extends above the gastroesophageal (GE) junction into the esophagus, the bulk of the tumor(therefore more than 50%)must involve the stomach. The tumor must not extend more than 2 cm into esophagus.
- Adequate hematological, renal and hepatic functions defined as:
- White blood cell count >= 4.0 x 109/L
- Platelet count >= 100 x 109/L
- Serum bilirubin <= 1.5 x upper normal limit
- Calculated Creatinine Clearance >=50 ml/min (cockcroft formula)
-Two equally functioning kidneys determined with standard technology (renogram)
- Tumor negative laparoscopy when CT suggests peritoneal carcinomatosis
- Written, voluntary informed consent (interval between information and consent at least 7 days)
- Patients must be accessible to follow up and management in the treatment center
- Patients must sufficiently understand the Dutch language and must be able to sign the informed consent document.
Exclusion criteria
- T1N0 tumors and in situ carcinoma (endoscopic ultrasound) are not eligible
- Distant metastases
- In case of only one functional kidney
- Previous or current malignancies at other sites than entry diagnosis except for adequately treated basal or squamous cell carcinoma of the skin, or curatively treated carcinoma in situ of the cervix uteri
- Prior chest or upper abdomen radiotherapy, prior systemic chemotherapy, or prior esophageal or gastric surgery.
- Evidence of serious active infections
- Severe cardiac and/or pulmonary failure, uncontrolled hypertension, angina pectoris
- Clinical signs of myocardial ischaemia
- Dementia or altered mental status that would prohibit the understanding and giving of informed consent
- Pregnant or lactating women. Sexually active patients of childbearing potential must implement effective contraceptive practices during the study when treated with chemotherapy
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2007-003669-41-NL |
| CCMO | NL18509.042.07 |