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A Multicenter Random Assignment Phase II Study of Irinotecan and Alvocidib (Flavopiridol) Versus Irinotecan Alone for Patients With p53 Wild Type Gastric Adenocarcinoma

Phase 2
18 Years
Open (Enrolling)
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

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Trial Information

A Multicenter Random Assignment Phase II Study of Irinotecan and Alvocidib (Flavopiridol) Versus Irinotecan Alone for Patients With p53 Wild Type Gastric Adenocarcinoma


I. To examine the antitumor efficacy of irinotecan (irinotecan hydrochloride) followed by
flavopiridol (alvocidib) (Arm A) and of irinotecan alone (Arm B) in patients with advanced
gastric/ gastroesophageal junction (GEJ) adenocarcinoma wild type for p53.


I. To evaluate the safety and toxicity of both study arms in patients with advanced
gastric/GEJ adenocarcinoma.

II. To examine other measures of antitumor activity in both study arms, including response
rate (in patients with measurable disease) and overall survival.


I. To evaluate pre- and post-treatment tumor biopsies for p21 and RAD51 homolog (S.
cerevisiae) (Rad51) expression in patients who agree to tumor biopsies (Memorial
Sloan-Kettering Cancer Center [MSKCC] and Weill-Cornell only).

II. To explore the response to irinotecan and flavopiridol and to irinotecan alone by
deoxyribonucleic acid (DNA) microarray technology on pre- and post-treatment tumor biopsies
(MSKCC and Weill-Cornell only).

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM A: Patients receive irinotecan hydrochloride intravenously (IV) over 30 minutes and
alvocidib IV over 1 hour on days 1 and 8. Courses repeat every 21 days in the absence of
disease progression or unacceptable toxicity.

ARM B: Patients receive irinotecan hydrochloride as in Arm A. Courses repeat every 21 days
in the absence of disease progression or unacceptable toxicity.

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

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

- 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

- 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

- 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

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Outcome Measure:

Progression-free survival (PFS) according to Response Evaluation Criteria in Solid Tumors (RECIST)

Outcome Time Frame:

Up to 3 months

Safety Issue:


Principal Investigator

Yelena Janjigian

Investigator Role:

Principal Investigator

Investigator Affiliation:

Memorial Sloan-Kettering Cancer Center at Saint Claires


United States: Food and Drug Administration

Study ID:




Start Date:

September 2009

Completion Date:

Related Keywords:

  • 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
  • Adenocarcinoma
  • Adenocarcinoma, Mucinous
  • Stomach Neoplasms



Memorial Sloan-Kettering Cancer Center at Saint ClairesDenville, New Jersey  07834