Clinical Trials /

MetronomIc CApecitabine and DOcetaxel as Second-line Chemotherapy for Advanced Gastric Cancer

NCT02007148

Description:

Second-line chemotherapy represents an option in gastric cancer, especially for patients with adequate performance status. Two randomized phase III trials comparing 2nd-line docetaxel with best-supportive care have reported a benefit in favor of chemotherapy. Capecitabine is a fluoropyrimidine carbamate, which has a broader spectrum of antitumor activity than other fluoropyrimidines. In gastric cancer xenografts. metronomic capecitabine inhibited angiogenesis, growth of gastric cancer and improved survival with less toxicity. Given its potential low toxicity, the combination of docetaxel and metronomic capecitabine needs to be evaluated to assess efficacy and tolerability in patients with advanced gastric cancer previously treated with a fluoropyrimidine-based and platinum-based chemotherapy.

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

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: MetronomIc CApecitabine and DOcetaxel as Second-line Chemotherapy for Advanced Gastric Cancer
  • Official Title: MetronomIc CApecitabine and DOcetaxel as Second-line Chemotherapy for Advanced Gastric Cancer Patients Previously Treated With Fluoropyrimidine and Platinum Agents MiCADO Study

Clinical Trial IDs

  • ORG STUDY ID: MICADO01
  • SECONDARY ID: MICADO
  • NCT ID: NCT02007148

Conditions

  • Gastric Adenocarcinoma
  • Gastroesophageal Junction Adenocarcinoma

Interventions

DrugSynonymsArms
capecitabinexelodamicado
Docetaxeltaxoteremicado

Purpose

Second-line chemotherapy represents an option in gastric cancer, especially for patients with adequate performance status. Two randomized phase III trials comparing 2nd-line docetaxel with best-supportive care have reported a benefit in favor of chemotherapy. Capecitabine is a fluoropyrimidine carbamate, which has a broader spectrum of antitumor activity than other fluoropyrimidines. In gastric cancer xenografts. metronomic capecitabine inhibited angiogenesis, growth of gastric cancer and improved survival with less toxicity. Given its potential low toxicity, the combination of docetaxel and metronomic capecitabine needs to be evaluated to assess efficacy and tolerability in patients with advanced gastric cancer previously treated with a fluoropyrimidine-based and platinum-based chemotherapy.

Detailed Description

      Despite a declining incidence in many developed countries, gastric cancer remains the second
      most common cause of cancer deaths, and it is responsible for about 12% of all cancer-related
      deaths worldwide. More than two-thirds of patients diagnosed with gastric cancer will have
      unresectable disease and despite the fact that surgical pathological resection can be
      curative for many patients, most of them develop recurrent disease. Evidence supports the use
      of palliative chemotherapy with the aims of improving symptoms, quality of life, and possibly
      prolonging survival. Combination chemotherapy regimens have been developed in the hopes of
      improving response rate and overall survival (OS). Unfortunately, the benefits of combination
      chemotherapy have been modest. In general, regimens containing fluoropyrimidine and platinum
      agents are widely accepted as potential standard therapies. Although a large proportion of
      patients with metastatic or recurrent gastric cancer may initially respond to chemotherapy,
      they ultimately progress. In addition, many patients have primary refractory disease. The
      median survival at progression after first-line chemotherapy for metastatic gastric cancer is
      about 2.5 months.

      Docetaxel is one of the most active single agents in the treatment of gastric cancer. In the
      first line setting, at a dose of 60-100 mg/m2 repeated every 3 weeks, response rates ranged
      from 17% to 20%. Docetaxel is the only taxane that has been evaluated in the context of a
      phase III study.

      Low-dose metronomic chemotherapy represents a new strategy to treat solid tumors by
      exhibiting stronger anti-angiogenic activity and less side effects, especially in combination
      with other anti-angiogenic agents. Capecitabine is a fluoropyrimidine carbamate, which has a
      broader spectrum of antitumor activity than other fluoropyrimidines. In gastric cancer
      xenografts. metronomic capecitabine inhibited angiogenesis, growth of gastric cancer and
      improved survival with less toxicity. In combination with other drugs, the treatment with
      metronomic capecitabine has proven its efficacy with minimal toxicity in breast cancer, in
      metastatic renal-cell carcinoma, in advanced adrenocortical carcinoma, in hepatocellular
      carcinoma, in prostate cancer.

      The "metronomic" strategy was also considered in pretreated elderly patients with advanced
      gastric cancer. Eligible patients with advanced gastric cancer were treated with capecitabine
      until disease progression or significant toxicity. Metronomic chemotherapy achieved a disease
      control rate at 8 weeks of 51.1% , and the objective response rate was 20.9% . The median
      time-to-progression and median overall survival were 3.6 months and 7.6 months, respectively.
      Grade II neutropenia and thrombocytopenia were observed in 13.3 and 2.2% of patients,
      respectively. Grade II/III nonhematological toxicities included diarrhea (4.4%), stomatitis
      (13.4%), and hand-foot syndrome (15.5%). No grade 4 toxicity, neutropenic fever or
      treatment-related deaths occurred.

      Based on these premises and to the fact that the role of metronomic chemotherapy remains
      controversial, its optimal therapeutic use has not yet been defined, we designed this phase
      II study with tha aim to assess efficacy and tolerability of metronomic capecitabine in
      combination with the conventional use of docetaxel in patients with advanced gastric cancer
      previously treated with a fluoropyrimidine-based and platinum-based chemotherapy.
    

Trial Arms

NameTypeDescriptionInterventions
micadoExperimentalCAPECITABINE 500 mg twice a day, orally, continuously DOCETAXEL 60 mg/sqm i.v. over 1 hr on day 1 cycles repeated every 3 weeks Duration of treatment: Chemotherapy should be continued until: progressive disease; unacceptable toxicities; patients' refusal; or upon investigator's judgement is in the best interest for the patient.
  • capecitabine
  • Docetaxel

Eligibility Criteria

        Inclusion Criteria:

          1. At least 18 years of age

          2. Histologically or cytologically confirmed gastric adenocarcinoma, including gastric or
             gastroesophageal-junction adenocarcinoma (GEJ)

          3. Measurable disease based on computed tomography

          4. Eastern Cooperative Oncology Group performance status 0 or 1

          5. Treatment with only 1 prior regimen (as first-line therapy) that must have included a
             fluoropyrimidine and a platinum agent

          6. Disease progression after the start of the prior regimen based on computed tomography
             (or magnetic resonance imaging in the event of allergy to contrast medium)

          7. Adequate bone marrow, hepatic, and renal function,

          8. At least 4 weeks and recovery from effects of prior major surgery or radiation therapy

          9. If previously administered as treatment for gastric cancer, prior to study entry a
             washout period equivalent to at least 5 half-lives for antibodies and of at least 28
             days for chemotherapy (Concurrent use of bisphosphonates is permitted.)

         10. Ability to swallow an oral solid-dosage form of medication, including when a feeding
             tube is present

         11. A negative serum pregnancy test within 7 days prior to accrual in women of
             childbearing potential

         12. Agreement to use an effective form of contraception

         13. Signed written informed consent.

         14. Ability to comprehend and to comply with the requirements of the study.

        Exclusion Criteria:

          1. Squamous cell gastric carcinoma

          2. Bone-only metastatic disease

          3. History or presence of brain metastasis or leptomeningeal disease

          4. Operable gastric or GEJ cancer

          5. Herceptin 2 (HER2) -positive disease if the subject has not previously been treated
             with an anti-HER2 agent

          6. Uncontrolled diarrhea, defined as more than 3 loose bowel movements above the
             subject's usual number of bowel movements on at least 3 days within the 14 days prior
             to study entry

          7. Nausea or vomiting for at least 3 consecutive days within the 14 days prior to study
             entry despite the administration of standard antiemetic therapy

          8. Known malabsorptive disorder

          9. Second cancer (except for adequately treated basal cell or squamous cell skin cancer,
             in situ cervical cancer, or other cancer for which the subject has been disease-free
             for 5 or more years)

         10. Human immunodeficiency virus infection based on history of positive serology

         11. Significant medical disease other than gastric cancer, including but not limited to
             uncontrolled diabetes mellitus, active angina or heart failure, uncontrolled
             hypertension, or an active psychiatric condition that would prevent consistent and
             compliant participation in the study

         12. Presence of neuropathy > Grade 1

         13. Prior treatment including docetaxel

         14. Prior radiation therapy to more than 25% of the bone marrow

         15. Need for other anticancer treatment (such as chemotherapy, radiation therapy, or
             biologic therapy with an approved or investigational agent) while receiving protocol
             therapy

         16. History of severe or unexpected reaction to fluoropyrimidine therapy

         17. History of hypersensitivity to fluoropyrimidine agents or any of their ingredients.

         18. Known dihydropyrimidine dehydrogenase deficiency

         19. Pregnancy or lactation
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:tumor response
Time Frame:6 months
Safety Issue:
Description:CT scan evaluated with RECIST 1.1

Secondary Outcome Measures

Measure:progression-free survival
Time Frame:6 months
Safety Issue:
Description:progression-free survival
Measure:overall survival
Time Frame:12 months
Safety Issue:
Description:overall survival
Measure:number of patients with Adverse Events
Time Frame:6 months
Safety Issue:
Description:number of patients with Adverse Events
Measure:time to treatment failure
Time Frame:6 months
Safety Issue:
Description:time to treatment failure

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:International Group of Endovascular Oncology

Trial Keywords

  • gastric adenocarcinoma,
  • capecitabine,
  • second line treatment,
  • recurrent or metastatic disease,
  • overall survival,
  • tumor response,
  • quality of life

Last Updated

February 26, 2019