Genotype Guided Chemotherapy in Gastric Cancer Patients

NCT02204306 | Completed Phase 2 DMC

• 2 other identifiers: 1000 Talents-CSU-GC1000 Plan
• Study Type: interventional
• Target: 330
• Locations: 1 country
• Sites: 1

Brief Summary

In gastric cancer patients treated with 5-FU and cisplatin, higher tumor TS levels were associated with a less favorable response (29% vs. 68%; p=0.024). Similarly, in a study in which patients were treated with high dose 5-FU, patients with high TS expression had a response rate of only 12.5%. Conversely a response rate of 92.9% was observed in patients with low tumor TS expression. A longer but not statistically significant survival advantage was observed in patients with the TSER\*2 allele compared with the TSER\*3/\*3 patients. Additionally, a review by Patel et al. identified approximately 20 gastric cancer studies that have found a positive association between TSER genotype and clinical response (in either direction). Therefore, the primary goal of this proposal is to prospectively genotype patients, select patients with "good risk" TSER genotypes (TSER\*2\*/\*2 or \*2/\*3) and treat them with a standard 5-FU containing regimen (FOLFOX) in order to improve clinical outcomes, while randomize patients with the "poor risk" TSER genotype (\*3/\*3) to either the standard 5-FU containing regimen or another non-5-FU-based regimen (docetaxel/cisplatin).

Conditions

Metastatic Gastric Cancer

Outcome Measures

Primary Outcomes (1)

• disease control rate

  Determine whether the disease control rate (DCR) at 6 and 12 weeks in TSER\*3/\*3 patients with metastatic gastric cancer will be increased by using a non fluoropyrimidine containing regimen compared to fluoropyrimidine-containing regimens.

  6 and 12 weeks after the first chemotherapy

Secondary Outcomes (2)

• time to progression

  2 years maximum

• median overall survival

  2 years maximum

Other Outcomes (1)

• drug toxicities

  2 years maximum

Study Arms (3)

TSER *2/*2 *2/*3

OTHER

Patients with TSER \*2/\*2 \*2/\*3 genotypes will be assigned to this group and receive standard chemotherapy contains fluorouracil. (FOLFOX 6/XELOX/SOX)

Genetic: TSER

TSER*3/*3 (fluorouracil)

OTHER

Patients with TSER\*3/\*3 genotype will be randomly assigned to fluorouracil group (FOLFOX 6/XELOX/SOX) or non-fluorouracil group (DC or DO).

Genetic: TSER

TSER*3/*3 (non-fluorouracil)

OTHER

Patients with TSER\*3/\*3 genotype will be randomly assigned to fluorouracil group (FOLFOX 6/XELOX/SOX) or non-fluorouracil group (DC or DO).

Genetic: TSER

Interventions

TSER GENETIC

TS gene will be genotyped for each patients prior to chemotherapy. Patients will be assigned to different arms according to specific TSER genotype.

Also known as: TSER genotypes: *2/*2 *2/*3 *3/*3

TSER *2/*2 *2/*3; TSER*3/*3 (fluorouracil); TSER*3/*3 (non-fluorouracil)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically or cytologically confirmed metastatic adenocarcinoma of the stomach.
• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as \>20 mm with conventional techniques or as \>10 mm with spiral CT scan. See section 9.2 for the evaluation of measurable disease.
• No prior therapy for metastatic disease. Prior neo-adjuvant or adjuvant therapy is permitted if the disease free interval has been longer than 12 months.
• Age between 18 and 70 years. Because no dosing or adverse event data are currently available on the use of these regimens in patients \<18 years of age, children are excluded from this study.
• Life expectancy of greater than 3 months.
• ECOG performance status \< 2 (Karnofsky \>60%; see Appendix A).
• Patients must have normal organ and marrow function as defined below:
• Leukocytes \>3,000/microliter
• Absolute neutrophil count \>1,500/microliter
• Platelets \>100,000/microliter
• Total bilirubin \< 1.5 x ULN
• AST(SGOT)/ALT(SGPT) \<2.5 x ULN if not liver metastases \< 5 x ULN if known liver metastases
• Creatinine clearance \<1.5 x ULN
• Not pregnant. Not breast feeding. If the patient or partner is of childbearing potential, the couple will use adequate birth control in accordance with local IRB policies:
• For woman of childbearing potential:

You may not qualify if:

• Patients may not be receiving any other chemotherapy agents.
• Patients with known active brain metastases. Patients with treated brain metastases are permitted if stable off steroids for at least 30 days. A screening head CT/MRI is not required in asymptomatic patients for this protocol.
• History of allergic reactions to 5-FU, oxaliplatin, docetaxel, or cisplatin.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements.
• Patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy. Therefore, HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with the chemotherapies.

Sponsors & Collaborators

• Central South University: lead

Study Sites (1)

Institute of Clinical Pharmacology

Changsha, Hunan, 410005, China

Location

MeSH Terms

Conditions

Stomach Neoplasms

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: July 21, 2014
• First Posted: July 30, 2014
• Study Start: April 1, 2014
• Primary Completion: March 1, 2016
• Study Completion: December 1, 2016
• Last Updated: November 18, 2019

Record last verified: 2019-11

Locations

CN (1)