Irinotecan Hydrochloride With or Without Alvocidib in Treating Patients With Advanced Stomach Cancer or Gastroesophageal Junction Cancer

OBJECTIVES:

Primary

- To examine the antitumor efficacy of irinotecan hydrochloride with vs without alvocidib
in patients with p53 wild type advanced gastric or gastroesophageal junction
adenocarcinoma.

Secondary

- To evaluate the safety and toxicity of these regimens in these patients.

- To examine other measures of antitumor activity of these regimens, including response
rate (in patients with measurable disease) and overall survival.

Tertiary

- To evaluate pre- and post-treatment tumor biopsy samples for p21 and Rad51 expression
in patients who agree to undergo tumor biopsies (Memorial Sloan-Kettering Cancer Center
[MSKCC] only).

- To explore the response to these regimens by DNA microarray technology using pre- and
post-treatment tumor biopsy samples (MSKCC only).

OUTLINE: This is a multicenter study. Patients are randomized to 1 of 2 treatment arms.

- Arm I: Patients receive irinotecan hydrochloride IV over 30 minutes and alvocidib IV
over 1 hour on days 1 and 8.

- Arm II: Patients receive irinotecan hydrochloride IV over 30 minutes on days 1 and 8.

In both arms, courses repeat every 21 days in the absence of disease progression or
unacceptable toxicity.

Tumor tissue samples may be collected pre- and post-treatment for correlative laboratory
studies.

After completion of study treatment, patients are followed up every 3 months for 1 year.

DISEASE CHARACTERISTICS:

- Pathologically confirmed adenocarcinoma of the stomach or gastroesophageal junction
(Siewert type I, II, or II)

- Advanced disease not amenable to surgical resection

- Tumor tissue must be available for assessment of p53 status (an additional tumor
biopsy is required if there is not sufficient primary tumor tissue available for
microdissection under high power microscopy, DNA extraction, and sequencing for p53
mutations)

- Tumor must be p53 wild type, defined as ≤ 20% nuclear staining on IHC

- Radiographically evaluable disease (measurable or non-measurable disease)

- Measurable disease is defined as that which can be measured in ≥ 1 dimension as
> 20 mm by 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 disease

- Must have received 1 prior chemotherapy regimen for unresectable or metastatic
disease (not including treatment administered in the adjuvant and/or neoadjuvant
setting)

- No known CNS metastasis

PATIENT CHARACTERISTICS:

- Karnofsky performance status 60-100%

- WBC ≥ 3,000/mm^3

- ANC ≥ 1,000/mm^3

- Platelet count ≥ 75,000/mm^3

- Serum creatinine ≤ 2 mg/dL

- Total serum bilirubin ≤ 2.0 mg/dL

- Patients with a serum bilirubin > 2.0 mg/dL who have Gilbert disease may be
eligible on a case-by-case basis after discussion with the principal
investigator

- Serum AST and ALT ≤ 3 times upper limit of normal (ULN) (≤ 5 times ULN in the case of
liver metastases)

- CD4 count > 200/mm^3

- Not pregnant or nursing during and for ≥ 2 months after completion of study treatment

- Negative pregnancy test

- Fertile patients must use effective contraception during and for ≥ 2 months after
completion of study treatment

- Has the mental capacity to understand the nature of this study and provide informed
consent

- No ongoing toxicity ≥ grade 2 from prior treatment

- No ongoing uncontrolled illness including, but not limited to, any of the following:

- Active infection

- Symptomatic congestive heart failure

- Myocardial infarction within the past 6 months

- New cardiac arrhythmia within the past 6 months

- No diagnosis of active HIV infection

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- No prior irinotecan hydrochloride or alvocidib

- At least 2 weeks since prior chemotherapy (4 weeks if the last regimen included
carmustine or mitomycin C), antiangiogenic therapy, other targeted therapy, or
radiotherapy

- No other concurrent investigational agents

- No concurrent antiretroviral therapy