Irinotecan Hydrochloride With or Without Alvocidib in Treating Patients With Advanced Stomach or Gastroesophageal Junction Cancer That Cannot Be Removed By Surgery

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00991952
First received: October 7, 2009
Last updated: May 9, 2014
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
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
Drug: alvocidib
Drug: irinotecan hydrochloride
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Multicenter Random Assignment Phase II Study of Irinotecan and Alvocidib (Flavopiridol) Versus Irinotecan Alone for Patients With p53 Wild Type Gastric Adenocarcinoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Overall Response Rate [ Time Frame: From the start of treatment for up to 3 months ] [ Designated as safety issue: No ]
    Response was determined as indicated in the protocol.


Enrollment: 19
Study Start Date: September 2009
Study Completion Date: April 2014
Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A (irinotecan hydrochloride, alvocidib)
Patients receive irinotecan hydrochloride 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.
Drug: alvocidib
Given IV
Other Names:
  • FLAVO
  • flavopiridol
  • HMR 1275
  • L-868275
Drug: irinotecan hydrochloride
Given IV
Other Names:
  • Campto
  • Camptosar
  • CPT-11
  • irinotecan
  • U-101440E
Other: laboratory biomarker analysis
Correlative studies
Active Comparator: Arm B (irinotecan hydrochloride)
Patients receive irinotecan hydrochloride as in Arm A. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Drug: irinotecan hydrochloride
Given IV
Other Names:
  • Campto
  • Camptosar
  • CPT-11
  • irinotecan
  • U-101440E
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

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.

TERTIARY OBJECTIVES:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00991952

Locations
United States, California
City of Hope
Duarte, California, United States, 91010
UC Davis Comprehensive Cancer Center
Sacramento, California, United States, 95817
United States, Illinois
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States, 60637-1470
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
Sponsors and Collaborators
Investigators
Principal Investigator: Yelena Janjigian Memorial Sloan-Kettering Cancer Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00991952     History of Changes
Other Study ID Numbers: NCI-2011-03825, NCI-2011-03825, CDR0000655636, MSKCC-8060, 8060, 09-074, 8060, N01CM00038
Study First Received: October 7, 2009
Results First Received: November 7, 2013
Last Updated: May 9, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Adenocarcinoma
Stomach Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Irinotecan
Camptothecin
Flavopiridol
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Growth Inhibitors
Growth Substances
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on July 24, 2014