Study of TKI 258 in Combination With Xeloda and Oxaliplatin in Advanced Colorectal and Gastric Cancer

March 25, 2016 updated by: National Cancer Centre, Singapore

A Phase 1 Study of TKI 258 in Combination With Xeloda and Oxaliplatin in Upfront Treatment of Advanced Colorectal and Gastric Cancer With a Dose Expansion Cohort in Advanced Gastric Cancer

Standard "3+3" dose escalation design of TKI258/XELOX in advanced gastric/gastro-oesophageal and colorectal cancer.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

This is a "3+3" dose escalation design with 4 pre-defined TKI258 dose levels (200mg, 300mg, 400mg and 500mg daily with 5 days on and 2 days off schedule) in combination with a fixed standard dose of XELOX (Capecitabine and Oxaliplatin) to establish the recommended phase 2 dose.

Study Type

Interventional

Enrollment (Actual)

3

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Singapore
      • Singapore, Singapore
        • National Cancer Centre Singapore

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Patients must have histologically confirmed gastric, gastro-oesophageal or colorectal adenocarcinoma.
  2. The gastric or gastro-oesophageal cancer must be locally advanced unresectable or metastatic. Colorectal cancer must be metastatic and for which subsequent resection of all metastatic disease is assessed not to be feasible.
  3. Age >18 years.
  4. Eastern Cooperative Oncology Group (ECOG) performance status <2 (Karnofsky >60%, see Appendix A).
  5. Life expectancy of greater than 3 months

  6. Patients must have normal organ and marrow function as defined below:

    • leukocytes >3,000/mcL
    • absolute neutrophil count >1,500/microliter (mcL) TKI258/XELOX phase 1 protocol version 3.3 Dated 30 November 2011 1 3
    • platelets >100,000/mcL
    • total bilirubin <= 1.5 x upper limit of normal (ULN)
    • aspartate aminotransferase (AST)/alanine aminotransferase (ALT) <2.5 X institutional upper limit of normal
    • creatinine within normal institutional limits OR
    • creatinine clearance >55 mL/min for patients with creatinine levels above institutional normal.
  7. The effects of TKI258 and XELOX on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
  8. Baseline left ventricular ejection fraction (LVEF) >= 50%
  9. Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

  1. Patients are not considered to have a "currently active" malignancy if they have TKI258/XELOX phase 1 protocol version 3.3 Dated 30 November 2011 1 4 completed therapy and are considered to have a less than 30% risk of relapse.
  2. Pregnant women are excluded from this study because of 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 TKI258 or XELOX, breastfeeding should be discontinued if the mother is treated with TKI258 or XELOX.
  3. Patients with prior history of transient ischemia attack or cerebrovascular disease or prior history of ischemia heart disease or myocardia infarction and 2 or more risk factors: ever smoker with > 30 packs per year exposure or on medication for diabetes mellitus or hypertension or hyperlipidemia.

  4. In addition for the Beginning at dose expansion cohort, the following exclusion criteria apply:

    • Patients who are not agreeable for collection of tumor tissue for correlative studies
    • Patients from whom tumor tissue for correlative studies cannot be safely obtained.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: TKI258 combined with Xeloda/Oxaliplatin
TKI258 200 mg once a day (OD) 5 days on/2 days off Capecitabine (Xeloda) 2000 mg/m2 bid d1-14 Oxaliplatin 130mg/m2 d1 q21days
Drug: Xeloda,
Capecitabine (xeloda): 2000mg/m2, twice a day on Day 1-14;
Other Names:
  • capecitabine
Drug: Oxaliplatin
Oxaliplatin: 130mg/m2 day 1 every 21days
Drug: TKI258
4 dose levels of TKI258: 200mg, 300mg, 400mg, 500mg once daily, 5days on and 2 days off;

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Determine the recommended phase 2 dose of TKI258 in combination with XELOX (Capecitabine and Oxaliplatin)
Time Frame: 42 days
42 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Describe the toxic effects of TKI258 when administered in combination with XELOX chemotherapy.
Time Frame: one year
Toxicity will be graded using CTCAE version 4.0
one year
Measure the Area under the plasma concentration versus time curve (AUC) of TKI258 at specific timepoints
Time Frame: 42 days
42 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Centre, Singapore

Collaborators

Novartis

Investigators

  • Principal Investigator: Iain BH Tan, Dr, National Cancer Centre, Singapore

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2011

Primary Completion (Actual)

January 1, 2012

Study Completion (Actual)

January 1, 2012

Study Registration Dates

First Submitted

May 14, 2012

First Submitted That Met QC Criteria

March 25, 2016

First Posted (Estimate)

March 28, 2016

Study Record Updates

Last Update Posted (Estimate)

March 28, 2016

Last Update Submitted That Met QC Criteria

March 25, 2016

Last Verified

March 1, 2016

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCC 10-03

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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