NCT00064259

Brief Summary

Drugs used in chemotherapy such as cisplatin and fluorouracil use different ways to stop tumor cells from dividing so they stop growing or die. Oblimersen may increase the effectiveness of chemotherapy by making tumor cells more sensitive to the drugs. This phase I/II trial is studying the side effects and best dose of oblimersen when given with cisplatin and fluorouracil and to see how well they work in treating patients with locally advanced, recurrent, or metastatic cancer of the esophagus, gastroesophageal junction, or stomach.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
15

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Jun 2003

Longer than P75 for phase_1

Geographic Reach
1 country

1 active site

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

June 1, 2003

Completed
1 month until next milestone

First Submitted

Initial submission to the registry

July 8, 2003

Completed
1 day until next milestone

First Posted

Study publicly available on registry

July 9, 2003

Completed
6.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2010

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2010

Completed
5.4 years until next milestone

Results Posted

Study results publicly available

June 29, 2015

Completed
Last Updated

February 17, 2021

Status Verified

January 1, 2021

Enrollment Period

6.7 years

First QC Date

July 8, 2003

Results QC Date

June 10, 2015

Last Update Submit

January 29, 2021

Conditions

Outcome Measures

Primary Outcomes (1)

  • Maximum Tolerated Dose (MTD) of Oblimersen in Combination With Cisplatin and 5-FU

    Adverse events were evaluated according to the National Cancer Institute Common Toxicity Criteria (version 2.0). DLT was defined as grade 3 to 4 hematologic toxicity lasting more than 1 week after 5-FU/cisplatin, grade 3 to 4 nausea or vomiting occurring later than 11 days after cisplatin, grade 3 to 4 diarrhea occurring later than 10 days after 5-FU, and grade 3 to 4 mucositis at the beginning of the next cycle.

    21 days

Secondary Outcomes (1)

  • Microarray Data

    Up to 12 weeks

Study Arms (1)

Treatment (oblimersen sodium)

EXPERIMENTAL

Phase I: Patients receive oblimersen IV continuously on days 1-7, fluorouracil IV continuously on days 4-8, and cisplatin IV on day 4. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of oblimersen until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. An additional 12 patients are treated at the MTD. Phase II: Patients receive treatment as in phase I with oblimersen at the MTD.

Biological: oblimersen sodiumDrug: cisplatinDrug: fluorouracil

Interventions

Given IV

Also known as: augmerosen, G3139, G3139 bcl-2 antisense oligodeoxynucleotide, Genasense
Treatment (oblimersen sodium)

Given IV

Also known as: CACP, CDDP, CPDD, DDP
Treatment (oblimersen sodium)

Given IV

Also known as: 5-fluorouracil, 5-Fluracil, 5-FU
Treatment (oblimersen sodium)

Eligibility Criteria

Age19 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Histologically or cytologically confirmed adenocarcinoma of the esophagus, gastro- esophageal junction, or stomach; patients with squamous cell carcinoma of the esophagus will also be eligible, patients must have locally advanced, recurrent or metastatic disease, not amenable to complete surgical resection or definitive radiation therapy
  • Measurable and/or evaluable disease
  • May have had prior surgery, radiation therapy, combined modality chemo- radiation, or at most one prior chemotherapy regimen for advanced, recurrent or metastatic disease;
  • Life expectancy of greater than 12 weeks
  • ECOG performance status =\<2 (Karnofsky \>= 60%)
  • Absolute neutrophil count \>= 1,500/uL
  • Platelets \>= 100,000/uL
  • Total bilirubin within normal institutional limits
  • Creatinine =\< 1.5 OR creatinine clearance \>= 60 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal
  • Ability to understand and the willingness to sign a written informed consent document
  • Patients with accessible tumors are obliged to participate in biopsies 1 and 2; accessible tumors are defined as tumors reachable by EGD, or metastases, which, in the opinion of the treating physician can be biopsied with commonly utilized biopsy methods (such as CT guided biopsy); biopsy #3 on day 6 is optional; patients who do not have have accessible tumor tissue may participate in the study if at least one tumor deposit is measurable

You may not qualify if:

  • Patients who have had chemotherapy or radiotherapy within 21 days (6 weeks for nitrosoureas or mitomycin C, two weeks if prior treatment was a weekly regimen) prior to entering the study or those who have not recovered from adverse events (grade 2 or worse) due to agents administered earlier
  • Patients who have had photodynamic therapy within 4 weeks of proposed study entry will be excluded; patients will be allowed to receive concurrent photodynamic therapy for obstruction untreatable by stent, laser, or dilation; patients who do require concurrent photodynamic therapy and who are participating in the serial biopsy portion of the study must wait until after cycle 1 and its biopsies are completed
  • Patients may not be receiving any other investigational agents
  • Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to anti- sense oligonucleotides, cisplatin, fluorouracil or other agents used in the study
  • Patients may not have received G3139 previously
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study because G3139 is an anti- sense oligonucleotide agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with G3139, breastfeeding should be discontinued if the mother is treated with G3139; these potential risks may also apply to other agents used in this study
  • Because patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy, HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with G3139 or other agents administered during the study; appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Montefiore Medical Center

The Bronx, New York, 10467-2490, United States

Location

Related Publications (1)

  • Raab R, Sparano JA, Ocean AJ, Christos P, Ramirez M, Vinciguerra V, Kaubisch A. A phase I trial of oblimersen sodium in combination with cisplatin and 5-fluorouracil in patients with advanced esophageal, gastroesophageal junction, and gastric carcinoma. Am J Clin Oncol. 2010 Feb;33(1):61-5. doi: 10.1097/COC.0b013e3181a31ad0.

MeSH Terms

Conditions

Adenocarcinoma Of EsophagusEsophageal NeoplasmsStomach NeoplasmsEsophageal Squamous Cell Carcinoma

Interventions

oblimersenCisplatinFluorouracil

Condition Hierarchy (Ancestors)

Gastrointestinal NeoplasmsDigestive System NeoplasmsNeoplasms by SiteNeoplasmsHead and Neck NeoplasmsDigestive System DiseasesEsophageal DiseasesGastrointestinal DiseasesStomach DiseasesCarcinoma, Squamous CellCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasms, Squamous Cell

Intervention Hierarchy (Ancestors)

Chlorine CompoundsInorganic ChemicalsNitrogen CompoundsPlatinum CompoundsUracilPyrimidinonesPyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic Compounds

Results Point of Contact

Title
NYCC Regulatory Coordinator
Organization
Montefiore Medical Center - New York

Study Officials

  • Andreas Kaubisch

    Montefiore Medical Center

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
LTE60
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 8, 2003

First Posted

July 9, 2003

Study Start

June 1, 2003

Primary Completion

February 1, 2010

Study Completion

February 1, 2010

Last Updated

February 17, 2021

Results First Posted

June 29, 2015

Record last verified: 2021-01

Locations