Integration of Cetuximab, in Combination With Local Radiotherapy, in Perioperative Chemotherapy of Resectable and Locally Advanced Gastric Cancer. A Pilot Phase Ib-trial
18 Years
75 Years
Both
Gastric Cancer
Trial Information
Integration of Cetuximab, in Combination With Local Radiotherapy, in Perioperative Chemotherapy of Resectable and Locally Advanced Gastric Cancer. A Pilot Phase Ib-trial
OBJECTIVES:
Primary
• To determine the maximum tolerated dose of radio-chemo-immunotherapy - in patients with
localized or locally advanced gastric cancer
Secondary
- To determine the efficacy, as measured by major histopathological response rates (tumor
regression grade 1 and 2)
- Metabolic response
- Secondary resectability
- R-0 resection rate
- Surgical morbidity
- Toxicity
- Overall survival
- Time to local and systemic progression after R0-resection
- Feasibility
OUTLINE: Prospective, multicenter, open-label dose escalating phase Ib trial
During induction chemo-immuno-therapy, patients receive cetuximab IV over 1-2 hours on days
1, cisplatin IV over 1 hour on day 1 and capecitabine twice daily per os from the evening of
day 1 to the morning of day 15. Treatment repeats every 3 weeks for up to 3 courses in the
absence of disease progression or unacceptable toxicity.
Radiotherapy will start after the end of the third cycle of chemotherapy and be performed
concomitantly with weekly cetuximab and cisplatin.
Cohorts of 3-6 patients receive escalating doses of radiotherapy (levels of 36/39.6/45 Gy)
until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose
preceding that at which maximum 3 of 12 patients experience dose-limiting toxicity.
Gastric resection should be performed within 4-6 weeks after completion of neoadjuvant
treatment.
4-6 weeks after surgery, a further 3 cycles of chemo-immuno-therapy will be administered if
the patient has recovered from surgery and the treatment is considered as feasible by the
investigator.
For note: Cisplatin may be replaced by oxaliplatin during induction chemotherapy and
postoperative chemotherapy. In case if oxaliplatin is used to replace cisplatin during
induction chemotherapy, replacement of cisplatin by oxaliplatin during
radio-chemo-immunotherapy may also be considered by the investigator.
Capecitabine may be replaced by infusional 5-FU on day 1-5 every 21 days in case of
contraindications to capecitabine.
In case if both cisplatin and capecitabine are to be replaced, 4 cycles of FOLFOX-6 (d-l
leucovorin, followed by 5-FU bolus and a continuous infusion of over 46 hours every 2 weeks
should be administered in combination with cetuximab).
Patients undergo tumor tissue and blood sample collection periodically for biological
studies. Samples are analyzed for major histopathological response.
After completion of study treatment, patients are followed periodically for at least 5
years.
Inclusion Criteria:
- Histologically proven, localized (UICC stage I-II, T1-2, N1-2 or T3N0) or locally
advanced (UICC stage III, T3-4, N+) gastric or Siewert Type II and III GE-junction
adenocarcinoma. Tumor stage is determined by thoraco-abdominal CT-scan, EUS, as well
as mandatory laparoscopy to rule out peritoneal carcinomatosis within 28 days prior
to registration.
- ECOG-status 0-1
- Hematologic, liver, and renal function normal
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 12 months after
completion of study treatment
Exclusion Criteria:
- Peritoneal carcinomatosis, as diagnosed by mandatory laparoscopy or distant
metastasis
- Concurrent treatment with other experimental drugs or other anti-cancer therapy, or
treatment within a clinical trial within 30 days prior to trial entry
- Severe or uncontrolled cardiovascular disease (congestive heart failure NYHA III or
IV, no myocardial infarction within the last 12 months, unstable angina pectoris, or
significant arrhythmia)
- Active or uncontrolled infection.
- Definitive contraindications for the use of corticosteroids as premedication
- Prior systemic (chemo- or targeted) treatment. Prior radiotherapy to the upper
abdomen
- Any contraindication to treatment with cetuximab, capecitabine or cisplatin
- Any concomitant medication which is contraindicated for use with the trial drugs,
such as sorivudin or brivudin
- HER-2 over expression, as determined by immunohistochemistry (IHC 3+) or the
combination of IHC and FISH (IHC 2+/FISH+)
- Previous malignancy within 5 years, with the exception of adequately treated cervical
carcinoma in situ or localized non-melanoma skin cancer
- Known hypersensitivity against any of the study drugs (cetuximab, cisplatin or
capecitabine) or any component of the trial drugs
- Known deficit of dihydropyrimidine dehydrogenase
- Pre-existing peripheral neuropathy > grade I
- Due to known interactions of coumarin antagonists (e.g. warfarin) and capecitabine
patients requiring oral anticoagulation should be included in the study only after a
switch from oral anticoagulation to low molecular weight heparin
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Dose limiting toxicity
Outcome Time Frame:
Patients will be evaluated for dose limiting toxicities until four weeks after combined radio-chemo-immunotherapy
Safety Issue:
Yes
Principal Investigator
Anna Dorothea Wagner, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Centre Hospitalier Universitaire Vaudois
Authority:
Switzerland: Swissmedic
Study ID:
CHUV-CePO-B354re (gastric)
NCT ID:
NCT01611506
Start Date:
February 2012
Completion Date:
December 2012
Related Keywords:
- Gastric Cancer
- Stomach Neoplasms
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