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Gastric CancerPhase 1/2NCT01611506

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

A Phase 1/2 study testing Cetuximab, Capecitabine and Cisplatin in people with Gastric Cancer, run by Dr Anna Dorothea Wagner at 1 site in Switzerland.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Gastric Cancer
What is being tested?
Cetuximab, Capecitabine and Cisplatin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1 participants
Where
1 siteSwitzerland
Study dates
Feb 2012to Dec 2012
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 14Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

Switzerland1 site
  • Centre Hospitalier Universitaire Vaudois

    Lausanne

Other trials in Switzerland

About this study

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

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.

Read the detailed description

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.

Conditions
Gastric Cancer
Medical subject headings
Stomach Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CetuximabBiological

    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

  • CapecitabineDrug

    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

  • CisplatinDrug

    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

Study groups in NCT01611506
Study groupRoleWhat they receive
Cetuximab, capecitabine, cisplatin based chemoradiationExperimentalInduction 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.
Receives: Biological: Cetuximab; Drug: Capecitabine; Drug: Cisplatin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dose limiting toxicity

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

Secondary outcomes (9)
  1. Metabolic response

    Metabolic response, as measured by F-18-FDG PET-CT measurement of SUVmax

    Measured: After 6 weeks of chemo-immunotherapy

  2. Secondary resectability

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

  3. Major histopathological response rate

    Measured: at surgery 4-6 weeks after end of neoadjuvant therapy

  4. R-0 resection rate

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

  5. Surgical morbidity

    Measured: within 30 days after surgery

  6. Overall survival

    Measured: Measured by median, 1-, 2-, and 3- year survival rates

  7. Time to local and systemic progression after R0-resection

    Measured: 5 years after completion of the trial treatement

  8. Feasibility

    Measured: Defined as completion of preoperative therapy (including surgery in patients with initially resectable tumors) and being alive 30 days postoperatively.

  9. Toxicity (according to NCI-CTCAE, Version 4.0)

    Measured: Within 30 days after completion of the trial treatement

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Jun 2012 (estimated)
  2. Study startFeb 2012
  3. Primary completionDec 2012
  4. Study completionDec 2012

Why it stopped: Outcome of EXPAND study (no benefit from adding cetuximab to the first-line chemotherapy in advanced gastric cancer in the overall patient population)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
1 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01611506
Sponsor's protocol ID
CHUV-CePO-B354re (gastric)
Status last verified
Jan 2013
First submitted
15 May 2012
Last updated
9 Jan 2013
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Cetuximab, Capecitabine and Cisplatin in people with Gastric Cancer, run by Dr Anna Dorothea Wagner at 1 site in Switzerland.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 9 Jan 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Outcome of EXPAND study (no benefit from adding cetuximab to the first-line chemotherapy in advanced gastric cancer in the overall patient population)). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose limiting toxicity (time frame: Patients will be evaluated for dose limiting toxicities until four weeks after combined radio-chemo-immunotherapy). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jan 2013.

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