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

This study has been terminated.
(Outcome of EXPAND study (no benefit from adding cetuximab to the first-line chemotherapy in advanced gastric cancer in the overall patient population))
Sponsor:
Information provided by (Responsible Party):
Dr Anna Dorothea Wagner, Centre Hospitalier Universitaire Vaudois
ClinicalTrials.gov Identifier:
NCT01611506
First received: May 15, 2012
Last updated: January 8, 2013
Last verified: January 2013
  Purpose

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.


Condition Intervention Phase
Gastric Cancer
Biological: Cetuximab
Drug: Capecitabine
Drug: Cisplatin
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Integration of Cetuximab, in Combination With Local Radiotherapy, in Perioperative Chemotherapy of Resectable and Locally Advanced Gastric Cancer. A Pilot Phase Ib-trial

Resource links provided by NLM:


Further study details as provided by Centre Hospitalier Universitaire Vaudois:

Primary Outcome Measures:
  • Dose limiting toxicity [ Time Frame: Patients will be evaluated for dose limiting toxicities until four weeks after combined radio-chemo-immunotherapy ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Metabolic response [ Time Frame: After 6 weeks of chemo-immunotherapy ] [ Designated as safety issue: No ]
    Metabolic response, as measured by F-18-FDG PET-CT measurement of SUVmax

  • Secondary resectability [ Time Frame: Decided by a multidisciplinary team 3-5 weeks after the end of neoadjuvant treatment ] [ Designated as safety issue: No ]
  • Major histopathological response rate [ Time Frame: at surgery 4-6 weeks after end of neoadjuvant therapy ] [ Designated as safety issue: No ]
  • R-0 resection rate [ Time Frame: at surgery 4-6 weeks after the end of neoadjuvant therapy ] [ Designated as safety issue: No ]
  • Surgical morbidity [ Time Frame: within 30 days after surgery ] [ Designated as safety issue: Yes ]
  • Overall survival [ Time Frame: Measured by median, 1-, 2-, and 3- year survival rates ] [ Designated as safety issue: No ]
  • Time to local and systemic progression after R0-resection [ Time Frame: 5 years after completion of the trial treatement ] [ Designated as safety issue: No ]
  • Feasibility [ Time Frame: Defined as completion of preoperative therapy (including surgery in patients with initially resectable tumors) and being alive 30 days postoperatively. ] [ Designated as safety issue: No ]
  • Toxicity (according to NCI-CTCAE, Version 4.0) [ Time Frame: Within 30 days after completion of the trial treatement ] [ Designated as safety issue: Yes ]

Enrollment: 1
Study Start Date: February 2012
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cetuximab, capecitabine, cisplatin based chemoradiation

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

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

Drug: Capecitabine

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

Drug: Cisplatin

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


  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01611506

Locations
Switzerland
Centre Hospitalier Universitaire Vaudois
Lausanne, Switzerland
Sponsors and Collaborators
Dr Anna Dorothea Wagner
Investigators
Principal Investigator: Anna Dorothea Wagner, MD Centre Hospitalier Universitaire Vaudois
  More Information

No publications provided

Responsible Party: Dr Anna Dorothea Wagner, Médecin associée, Centre Hospitalier Universitaire Vaudois
ClinicalTrials.gov Identifier: NCT01611506     History of Changes
Other Study ID Numbers: CHUV-CePO-B354re (gastric)
Study First Received: May 15, 2012
Last Updated: January 8, 2013
Health Authority: Switzerland: Swissmedic

Additional relevant MeSH terms:
Stomach Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Capecitabine
Cetuximab
Cisplatin
Fluorouracil
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors

ClinicalTrials.gov processed this record on July 24, 2014