Phase II Study of Cabazitaxel in Refractory Metastatic Gastric or Gastroesophageal Adenocarcinoma
Condition: Gastric Adenocarcinoma; Gastroesophageal Adenocarcinoma; Distal Esophageal Adenocarcinoma
MeSH terms: Adenocarcinoma
Intervention: Cabazitaxel
Intervention description: 20mg IV over 1 hour every 3 weeks
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 85.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Gastric Cancer

Summary:

      Cabazitaxel will be administered 20 mg/m2 IV over 1 hour every 3 weeks, as is the standard
      administration dose and schedule. This application is a non-labeled indication for
      cabazitaxel and will inform future drug development in gastroesophageal malignancies, where
      docetaxel remains an approved first line agent, but is not routinely used due to excessive
      toxicity and marginal efficacy.

      At the conclusion of this study, we hope to demonstrate activity of single agent cabazitaxel
      in refractory gastric cancer, with preferential activity in one or more gastric cancer
      subtypes
    

Eligibility criteria:

        Inclusion Criteria:

          1. Subject must have histologically or cytologically confirmed gastric, or
             gastroesophageal adenocarcinoma, or distal esophageal adenocarcinoma.

          2. Subject must have unresectable or metastatic gastroesophageal adenocarcinoma.

          3. Subject must have evaluable disease as per RECIST criteria.

          4. Subject must have had at least one prior cytotoxic chemotherapy regimen for
             unresectable or metastatic disease. Prior taxane therapy is allowed.

          5. Age >/=18 years old.

          6. ECOG performance status status >/= 2

          7. Subject must have normal organ and marrow function as defined below:

               -  WBC >/= 3,000/uL

               -  Total Bilirubin ≤ 1.5 x upper limits of normal

               -  AST (SGOT) ≤ 2.5 x upper limits of normal

               -  ALT (SGPT) ≤ 2.5 x upper limits of normal

               -  Hgb > 7.5 g/dl (without transfusion within 7 days)

               -  ANC > 1000 /ml

               -  Plt > 75 K/ml (without transfusion)

               -  Creatinine* < 2.0 g/dl *or a calculated creatinine clearance > 45/cc (using
                  Cockroft-Gault formula)

        9. Women of child-bearing potential and men must agree to use adequate contraception
        (hormonal or barrier method of birth control; abstinence) prior to study entry and for the
        duration of study participation. 10. Ability to understand and the willingness to sign a
        written informed consent document.

        Exclusion Criteria:

          1. Subject with previously untreated unresectable or metastatic gastroesophageal
             adenocarcinoma.

          2. Subject with more than 2 prior cytotoxic therapies (not including treatment
             administered for locally curable disease) for unresectable or metastatic
             gastroesophageal adenocarcinoma.

          3. Subject with CNS metastases with active neurologic dysfunction. These patients are
             excluded because of their poor prognosis and because they often develop progressive
             neurologic dysfunction that would confound the evaluation of neurologic and other
             adverse event.

          4. Significant medical co-morbidity that would preclude safe administration of cytotoxic
             therapy, including but not limited to:

             a.Cardiac disease i. Unstable angina ii. Myocardial infarction < 3 months prior to
             study initiation b. Ongoing serious infection i. Bacteremia or sepsis requiring
             intravenous antibiotics ii. HIV with AIDS defining illness c.Inadequate oral
             nutritional intake i. Requirement for daily intravenous fluids or total parenteral
             nutrition. d. Psychiatric illness/social situations that would limit compliance with
             study requirement

          5. Subject who has had chemotherapy or radiotherapy within 4 weeks (6 weeks for
             nitrosoureas or mitomycin C) prior to entering the study or those who have not
             recovered from prior treatment related toxicity with persistent symptoms >/= grade 2
             due to agents administered more than 4 weeks earlier.

          6. Subject may not receive another investigational agent.

          7. History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to Cabazitaxel, or to drugs formulated with polysorbate 80.

          8. Pregnant (positive pregnancy test) and lactating women are excluded from the study
             because the risks to an unborn fetus or potential risks in nursing infants are
             unknown.