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

NCT02720926 | Terminated Phase 1

• 1 other identifier: NCC 10-03
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Colorectal Cancer; Gastric Cancer

Outcome Measures

Primary Outcomes (1)

• Determine the recommended phase 2 dose of TKI258 in combination with XELOX (Capecitabine and Oxaliplatin)

  42 days

Secondary Outcomes (2)

• Describe the toxic effects of TKI258 when administered in combination with XELOX chemotherapy.

  one year

• Measure the Area under the plasma concentration versus time curve (AUC) of TKI258 at specific timepoints

  42 days

Study Arms (1)

TKI258 combined with Xeloda/Oxaliplatin

EXPERIMENTAL

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,; Drug: Oxaliplatin; Drug: TKI258

Interventions

Xeloda, DRUG

Capecitabine (xeloda): 2000mg/m2, twice a day on Day 1-14;

Also known as: capecitabine

TKI258 combined with Xeloda/Oxaliplatin

Oxaliplatin DRUG

Oxaliplatin: 130mg/m2 day 1 every 21days

TKI258 combined with Xeloda/Oxaliplatin

TKI258 DRUG

4 dose levels of TKI258: 200mg, 300mg, 400mg, 500mg once daily, 5days on and 2 days off;

TKI258 combined with Xeloda/Oxaliplatin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically confirmed gastric, gastro-oesophageal or colorectal adenocarcinoma.
• 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.
• Age \>18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status \<2 (Karnofsky \>60%, see Appendix A).
• Life expectancy of greater than 3 months
• 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.
• 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.
• Baseline left ventricular ejection fraction (LVEF) \>= 50%

You may not qualify if:

• 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.
• 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.
• 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.
• 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.

Sponsors & Collaborators

• National Cancer Centre, Singapore: lead
• Novartis: collaborator

Study Sites (1)

National Cancer Centre singapore

Singapore, Singapore

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Stomach Neoplasms

Interventions

Capecitabine; Oxaliplatin; 4-amino-5-fluoro-3-(5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl)quinolin-2(1H)-one

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Coordination Complexes; Organic Chemicals

Study Officials

• Iain BH Tan, Dr

  National Cancer Centre, Singapore

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: May 14, 2012
• First Posted: March 28, 2016
• Study Start: September 1, 2011
• Primary Completion: January 1, 2012
• Study Completion: January 1, 2012
• Last Updated: March 28, 2016

Record last verified: 2016-03

Data Sharing

• IPD Sharing: Will not share

Locations

SG (1)