Combination Chemotherapy, Cetuximab and Radiation for Patients With Localized Gastric Cancer

NCT01611506 | Terminated Phase 1 DMC

• 1 other identifier: CHUV-CePO-B354re (gastric)
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Radiotherapy is currently the most efficient way to induce pathologic responses, which are associated with a favorable prognosis in localized tumors. Novel radiotherapy techniques are associated with significantly less toxicity than traditional radiation protocols and permit to avoid the toxicity to adjacent organs. Established chemotherapy regimens, such as cisplatin and capecitabine, and monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Giving radiation therapy together with cisplatin and cetuximab before surgery aims to induce a pathological response and improve the prognosis after surgery. PURPOSE: This phase I trial is studying the side effects and best dose of radiation therapy when given together with cisplatin and cetuximab in treating patients who are undergoing surgery for locally advanced gastric cancer.

Conditions

Gastric Cancer

Outcome Measures

Primary Outcomes (1)

• Dose limiting toxicity

  Patients will be evaluated for dose limiting toxicities until four weeks after combined radio-chemo-immunotherapy

Secondary Outcomes (9)

• Metabolic response

  After 6 weeks of chemo-immunotherapy

• Secondary resectability

  Decided by a multidisciplinary team 3-5 weeks after the end of neoadjuvant treatment

• Major histopathological response rate

  at surgery 4-6 weeks after end of neoadjuvant therapy

• R-0 resection rate

  at surgery 4-6 weeks after the end of neoadjuvant therapy

• Surgical morbidity

  within 30 days after surgery

Study Arms (1)

Cetuximab, capecitabine, cisplatin based chemoradiation

EXPERIMENTAL

Induction chemotherapy: 3 cycles (of 3 weeks) with capecitabine, cisplatin and weekly cetuximab: Cetuximab 400mg/m2 (loading dose)on day 1 and 250mg/m2 weekly thereafter, Cisplatin 80mg/m2 on day 1 every three weeks, Capecitabine 1000mg/m2 twice daily from the evening of day 1 to the morning of day 15 within each 3 weeks cycle. Followed by: Radio-chemo-immunotherapy: Cetuximab 250mg/m2 weekly on day 1, Cisplatin 30mg/m2 weekly on day 1, Radiotherapy (dose escalation levels) 36/39.6/45 Gy(according to dose level) in 5 fractions of 1.8 Gy per week Surgery: Will be performed 4-6 weeks after neoadjuvant radiochemotherapy Postoperative treatment: 3 cycles of Chemo-immunotherapy with cetuximab, cisplatin and capecitabine -as described above- will be administered postoperatively if the patient has recovered adequately from surgery and the treatment is considered as feasible by the investigator.

Biological: Cetuximab; Drug: Capecitabine; Drug: Cisplatin

Interventions

Cetuximab BIOLOGICAL

Induction chemotherapy: Cetuximab 400mg/m2 (loading dose) on day 1 Cetuximab 250mg/m2 weekly thereafter Followed by: Cetuximab 250mg/m2 weekly on day 1 during chemoradiation Postoperative treatment: 3 cycles of Cetuximab 250mg/m2 weekly on day 1

Cetuximab, capecitabine, cisplatin based chemoradiation

Capecitabine DRUG

Induction chemotherapy: Capecitabine 1000mg/m2 twice daily from the evening of day 1 to the morning of day 15 within each 3 weeks cycle Postoperative treatment: Capecitabine 1000mg/m2 twice daily from the evening of day 1 to the morning of day 15 within each 3 weeks cycle

Cetuximab, capecitabine, cisplatin based chemoradiation

Cisplatin DRUG

Induction chemotherapy: Cisplatin 80mg/m2 on day 1 of each 21 day cycle Followed by: Cisplatin 30mg/m2 weekly on day 1 during chemoradiation Postoperative treatment: Cisplatin 80mg/m2 on day 1 of each 21 day cycle

Cetuximab, capecitabine, cisplatin based chemoradiation

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Dr Anna Dorothea Wagner: lead

Study Sites (1)

Centre Hospitalier Universitaire Vaudois

Lausanne, Switzerland

Location

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

Cetuximab; Capecitabine; Cisplatin

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Anna Dorothea Wagner, MD

  Centre Hospitalier Universitaire Vaudois

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Médecin associée

Study Record Dates

• First Submitted: May 15, 2012
• First Posted: June 5, 2012
• Study Start: February 1, 2012
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2012
• Last Updated: January 9, 2013

Record last verified: 2013-01

Locations

CH (1)