Irinotecan Hydrochloride With or Without Alvocidib in Treating Patients With Advanced Stomach or Gastroesophageal Junction Cancer That Cannot Be Removed By Surgery
Condition: Adenocarcinoma of the Gastroesophageal Junction; Diffuse Adenocarcinoma of the Stomach; Intestinal Adenocarcinoma of the Stomach; Mixed Adenocarcinoma of the Stomach; Recurrent Gastric Cancer; Stage IIIA Gastric Cancer; Stage IIIB Gastric Cancer; Stage IIIC Gastric Cancer; Stage IV Gastric Cancer
MeSH terms: Adenocarcinoma; Stomach Neoplasms
Intervention: alvocidib; irinotecan hydrochloride; laboratory biomarker analysis
Intervention description: Given IV; Given IV; Correlative studies
Intervention MeSH terms: Irinotecan; Alvocidib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 19.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase II trial studies how well giving irinotecan hydrochloride with or
      without alvocidib works in treating patients with advanced stomach or gastroesophageal
      junction cancer that cannot be removed by surgery. Drugs used in chemotherapy, such as
      irinotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by
      killing the cells or by stopping them from dividing. Alvocidib may stop the growth of tumor
      cells by blocking some of the enzymes needed for cell growth. It is not yet known whether
      irinotecan hydrochloride is more effective with or without alvocidib.
    

Eligibility criteria:

        Inclusion Criteria:

          -  The patient must have pathologically confirmed carcinoma of the stomach or GEJ
             (Siewert's type I, II, or III); confirmation will be performed locally at each
             participating institution

          -  The patient must have advanced disease not amenable to surgical resection

          -  Patients must have disease that can be evaluated radiographically; this may be
             measurable disease or non-measurable disease; measurable disease is defined as that
             which can be measured in at least one dimension as > 20 mm with conventional
             techniques, or > 10 mm by high resolution imaging; disease that is identified on
             radiology studies, but does not meet the criteria for measurable disease, is
             considered non-measurable

          -  The patient must have received one prior chemotherapy regimen for his or her
             unresectable or metastatic disease; this does not include therapy administered in the
             adjuvant or neoadjuvant setting

          -  At least 2 weeks must have elapsed since the patient received prior chemotherapy,
             anti-angiogenic therapy, or other targeted therapy; 2 weeks since prior radiation
             therapy; or, 4 weeks if the last regimen included carmustine (BCNU) or mitomycin C

          -  The patient must have a Karnofsky performance status of >= 60

          -  Serum creatinine =< 2 mg/dl

          -  Total serum bilirubin =< 2 mg/dl

               -  If the patient has Gilbert's disease and has a serum bilirubin greater than 2.0
                  mg/dl, the case must be discussed with the principal investigator; such a patient
                  may be considered eligible on a case-by-case basis

          -  Serum aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
             [SGOT])/ alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
             =< 3 times the upper limit of normal, or

          -  Serum AST (SGOT)/ ALT (SGPT) =< 5 times the upper limit of normal in case of liver
             metastases

          -  White blood cell (WBC) >= 3000/mm^3

          -  Absolute neutrophil count (ANC) >= 1000/mm^3

          -  Platelets >= 75,000/mm^3

          -  The patient must have available tumor tissue for assessment of p53 status by
             immunohistochemistry (IHC) (=< 20% cutoff for positivity)

          -  Tumor must be p53 wild type as defined as =< %20 nuclear staining on
             immunohistochemistry

          -  Women of child-bearing potential and sexually active males must be counseled to use an
             accepted and effective method of contraception (including intrauterine device [IUD],
             oral contraceptives, or barrier devices) while on treatment and for at least two
             months after their last treatment on this study; woman also must agree to refrain from
             nursing during the duration of this study and for at least two months after their last
             treatment on this study; women of child-bearing potential must have a negative serum
             pregnancy test to be eligible for this study

          -  The patient must have the mental capacity to understand the nature of this study and
             provide informed consent to participate

        Exclusion Criteria:

          -  The patient may not have previously received irinotecan or flavopiridol

          -  The patient may not be receiving any other investigational agents

          -  The patient may not have any ongoing grade 2 or greater toxicity from a prior
             treatment

          -  The patient may not have an ongoing uncontrolled illness including, but not limited to
             active infection, symptomatic congestive heart failure, myocardial infarction in the
             past 6 months, or new cardiac arrhythmia in the past 6 months

          -  Patients with a diagnosis of active human immunodeficiency virus (HIV) infection, on
             anti-retroviral therapy, or with a cluster of differentiation 4 (CD4) count less than
             200 are ineligible due to potential interactions between irinotecan, flavopiridol, and
             anti-retroviral medications as well as possible immunosuppressive activity of the
             study treatment