Clinical Trials /

CAPOX, Bevacizumab and Trastuzumab for Patients With HER2-Positive Metastatic Esophagogastric Cancer

NCT01191697

Description:

The purpose of this study is to determine the safety and effectiveness of a combination of chemotherapy, capecitabine and oxaliplatin, plus the antibodies bevacizumab and trastuzumab. Trastuzumab (also called Herceptin) is an antibody that attacks HER2 protein in tumor cells. Bevacizumab (also called Avastin) works by slowing or stopping the growth of cells in cancer tumors by decreasing the blood supply of the tumors. If blood supply is decreased, oxygen and nutrients that are needed for tumor growth are decreased. The chemotherapy used in this trial is called CAPOX, which is an abbreviation of capecitabine and oxaliplatin.

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Esophageal Adenocarcinoma
  • Gastric Adenocarcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: CAPOX, Bevacizumab and Trastuzumab for Patients With HER2-Positive Metastatic Esophagogastric Cancer
  • Official Title: Phase II Trial of CAPOX, Bevacizumab and Trastuzumab for Patients With HER2-Positive Metastatic Esophagogastric Cancer

Clinical Trial IDs

  • ORG STUDY ID: 09-457
  • NCT ID: NCT01191697

Conditions

  • Esophageal Cancer
  • Gastric Cancer

Interventions

DrugSynonymsArms
bevacizumabAvastin
trastuzumabHerceptin
oxaliplatin
capecitabinexeloda

Purpose

The purpose of this study is to determine the safety and effectiveness of a combination of chemotherapy, capecitabine and oxaliplatin, plus the antibodies bevacizumab and trastuzumab. Trastuzumab (also called Herceptin) is an antibody that attacks HER2 protein in tumor cells. Bevacizumab (also called Avastin) works by slowing or stopping the growth of cells in cancer tumors by decreasing the blood supply of the tumors. If blood supply is decreased, oxygen and nutrients that are needed for tumor growth are decreased. The chemotherapy used in this trial is called CAPOX, which is an abbreviation of capecitabine and oxaliplatin.

Detailed Description

      -  We recommend that the participants have a vascular access device, more commonly known as
           a PORT, inserted prior to starting chemotherapy. A port is a small device that is
           inserted under the skin (usually near the collar bone) by a minor surgical procedure and
           is then connected to one of the large veins inside the chest. The port will be used to
           give the intravenous medications.

        -  During the first cycle, the participant will receive trastuzumab intravenously on Day 1.
           Cycle 2 will then start one week later. On this day, bevacizumab will be given
           intravenously first followed by trastuzumab and then oxaliplatin. The participant will
           then start taking capecitabine tablets orally twice a day for 14 days. Each treatment
           cycle is 21 days long.

        -  Participants will have the following tests and procedures at specific time points during
           study treatment; physical exam, blood tests, CT scan, MUGA scan or echocardiogram, and
           urine test.
    

Trial Arms

NameTypeDescriptionInterventions

Eligibility Criteria

        Inclusion Criteria:

          -  Confirmed HER2-positive esophageal, GE junction or gastric adenocarcinoma that is
             metastatic or unresectable.

          -  All patients must have available tumor sample (either paraffin block or 15 freshly
             cut, unstained slides) prior to study entry.

        Part II: Patient must have primary esophagogastric tumor in place or other tumor that is
        accessible for mandatory biopsy.

          -  Measurable disease, defined in RECIST 1.1

          -  18 years of age or older

          -  Life expectancy of greater than 12 weeks

          -  ECOG performance status of 0 or 1

          -  Organ and marrow function as outlined in the protocol

          -  Women of child-bearing potential and men must agree to use adequate contraception
             during study participation and for 30 days from the date of the last study drug
             administration.

          -  Part II only: Participant agrees to undergo mandatory pre and post loading dose of
             trastuzumab biopsy for correlative science.

        Exclusion Criteria:

          -  Prior therapy with any of the following; capecitabine, oxaliplatin, bevacizumab or
             trastuzumab is not allowed. May have received and completed adjuvant therapy at least
             6 months prior to study entry or one prior therapy for metastatic disease as long as
             it did not include any of the above agents.

          -  Chemotherapy or radiotherapy to greater then 25% of bone marrow within 4 weeks prior
             to entering the study.

          -  Palliative radiation therapy to isolated bone metastasis within 2 weeks of initiating
             therapy.

          -  Major surgery, open biopsy, significant traumatic injury within 4 weeks prior to study
             entry,.

          -  Minor surgery, including placement of vascular access device within 7 days prior to
             the first dose of bevacizumab.

          -  Residual toxicity from prior chemotherapy and/or radiation therapy of Grade 2 or
             greater.

          -  Participants may not be receiving any concurrent investigational agents

          -  Active brain or other CNS metastasis by history or clinical examination.

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to capecitabine, bevacizumab or trastuzumab. No known allergy or
             hypersensitivity to Chinese hamster ovary, or any of the study agents. No known DPD
             deficiency.

          -  Warfarin is prohibited; anticoagulation using low molecular weight heparin is allowed.

          -  Uncontrolled, intercurrent illness

          -  Patients with a history of other malignancy are not eligible except for the following
             circumstances: disease-free for at least 3 years and are deemed to be at low risk for
             recurrence of that malignancy; cervical cancer in situ, basal cell or squamous cell
             carcinoma of the skin that was treated with curative intent within the past 5 years.

          -  Known HIV seropositivity, hepatitis C, acute or chronic hepatitis B or other serious
             active infection

          -  LVEF less than 50% as determined by MUGA scan or echocardiogram within 28 days prior
             to initiation of therapy

          -  Inadequately controlled hypertension

          -  History of prior hypertensive crisis or hypertensive encephalopathy

          -  History of any arterial thrombosis, CVA, TIA, MI or unstable angina in past 6 months.

          -  Evidence of bleeding diathesis or coagulopathy

          -  Serious, unhealed wounds, bone fractures or skin ulcers

          -  Pregnant or breast feeding

          -  Greater than grade 1 peripheral neuropathy at baseline

          -  Lack of physical integrity of the upper gastrointestinal tract or malabsorption
             syndrome.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Response Rate
Time Frame:2 years
Safety Issue:
Description:To determine the major response rate of CAPOX plus bevacizumab plus trastuzumab for patients with HER2-positive metastatic or unresectable esophagogastric adenocarcinoma.

Secondary Outcome Measures

Measure:Toxicity profile
Time Frame:2 years
Safety Issue:
Description:To determine the toxicity profile
Measure:Duration of response
Time Frame:2 years
Safety Issue:
Description:Determine the duration of response

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Dana-Farber Cancer Institute

Trial Keywords

  • HER2 positive

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