Trial Outcomes & Findings for Pharmacogenomically Selected Treatment for Gastric and Gastroesophageal Junction (GEJ) Tumors (NCT NCT00515216)

Results Overview

* ORR = complete response + partial response * Complete response - disappearance of all target and non-target lesions * Partial response - at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

26 participants

Primary outcome timeframe

2 years

Results posted on

2016-01-07

Participant Flow

This study opened to participant enrollment in June 2008 and closed to participant enrollment in October 2010.

Participant milestones

Participant milestones
Measure	Oxaliplatin/Leucovorin/5-FU "Good risk" patients with the TSER\2/\2 or \2/\3 genotype or low TS expression genotype Chemotherapy: 5-FU, leucovorin and oxaliplatin (FOLFOX)
Overall Study STARTED	26
Overall Study COMPLETED	25
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Oxaliplatin/Leucovorin/5-FU "Good risk" patients with the TSER\2/\2 or \2/\3 genotype or low TS expression genotype Chemotherapy: 5-FU, leucovorin and oxaliplatin (FOLFOX)
Overall Study Withdrawal by Subject	1

Baseline Characteristics

Pharmacogenomically Selected Treatment for Gastric and Gastroesophageal Junction (GEJ) Tumors

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Oxaliplatin/Leucovorin/5-FU n=26 Participants "Good risk" patients with the TSER\2/\2 or \2/\3 genotype or low TS expression genotype received treatment of oxaliplatin, leucovorin given over 2 hours along with 5-FU given as intravenous push followed by 5-FU given as intravenous infusion of 46 hours. This treatment was repeated every 2 weeks.
Age, Continuous	56 years n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants
Sex: Female, Male Male	16 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants
Race (NIH/OMB) White	23 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Region of Enrollment United States	26 participants n=5 Participants
TSER genotypes TSER2/2	5 participants n=5 Participants
TSER genotypes TSER2/3	21 participants n=5 Participants
ECOG Performance Status 0	5 participants n=5 Participants
ECOG Performance Status 1	13 participants n=5 Participants
ECOG Performance Status 2	8 participants n=5 Participants
Primary tumor type Gastric	19 participants n=5 Participants
Primary tumor type Gastroesophageal junction	7 participants n=5 Participants
Incidence of prior neoadjuvant or adjuvant therapy (>6 months)	8 percentage of participants n=5 Participants

PRIMARY outcome

Timeframe: 2 years

* ORR = complete response + partial response * Complete response - disappearance of all target and non-target lesions * Partial response - at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter

Outcome measures

Outcome measures
Measure	Oxaliplatin/Leucovorin/5-FU n=25 Participants "Good risk" patients with the TSER\2/\2 or \2/\3 genotype or low TS expression genotype received treatment of oxaliplatin, leucovorin given over 2 hours along with 5-FU given as intravenous push followed by 5-FU given as intravenous infusion of 46 hours. This treatment was repeated every 2 weeks.
Overall Response Rate (ORR)	39.1 percentage of participants Interval 22.2 to 59.2

SECONDARY outcome

Timeframe: 4 years

Outcome measures

Outcome measures
Measure	Oxaliplatin/Leucovorin/5-FU n=25 Participants "Good risk" patients with the TSER\2/\2 or \2/\3 genotype or low TS expression genotype received treatment of oxaliplatin, leucovorin given over 2 hours along with 5-FU given as intravenous push followed by 5-FU given as intravenous infusion of 46 hours. This treatment was repeated every 2 weeks.
Overall Survival	11.4 months Interval 6.3 to 16.3

SECONDARY outcome

Timeframe: 4 years

Progressive disease - at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions

Outcome measures

Outcome measures
Measure	Oxaliplatin/Leucovorin/5-FU n=25 Participants "Good risk" patients with the TSER\2/\2 or \2/\3 genotype or low TS expression genotype received treatment of oxaliplatin, leucovorin given over 2 hours along with 5-FU given as intravenous push followed by 5-FU given as intravenous infusion of 46 hours. This treatment was repeated every 2 weeks.
Progression-free Survival (PFS)	6.2 months Interval 5.2 to 8.6

SECONDARY outcome

Timeframe: 2 years

DCR - complete response, partial response, and stable disease * Complete response - disappearance of all target and non-target lesions * Partial response - at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter * Stable disease - neither sufficient shrinkage to qualify for partial response not sufficient increase to qualify for progressive disease

Outcome measures

Outcome measures
Measure	Oxaliplatin/Leucovorin/5-FU n=25 Participants "Good risk" patients with the TSER\2/\2 or \2/\3 genotype or low TS expression genotype received treatment of oxaliplatin, leucovorin given over 2 hours along with 5-FU given as intravenous push followed by 5-FU given as intravenous infusion of 46 hours. This treatment was repeated every 2 weeks.
Disease Control Rate (DCR)	95.7 percentage of participants Interval 79.0 to 99.2

SECONDARY outcome

Timeframe: 4 years

Population: This was not completed as the archived tumor samples were not of sufficient quality for DNA extraction or analysis.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 4 years

Population: 9 out of 25 participants had a partial response.

This outcome looks at what genotypes of the TYMS 5'-UTR TSER + G\>C (rs34743033) gene had a partial tumor response.

Outcome measures

Outcome measures
Measure	Oxaliplatin/Leucovorin/5-FU n=9 Participants "Good risk" patients with the TSER\2/\2 or \2/\3 genotype or low TS expression genotype received treatment of oxaliplatin, leucovorin given over 2 hours along with 5-FU given as intravenous push followed by 5-FU given as intravenous infusion of 46 hours. This treatment was repeated every 2 weeks.
Genetic Polymorphisms That May Alter Treatment Outcomes (Partial Response) TYMS, TSER2/2	5 participants
Genetic Polymorphisms That May Alter Treatment Outcomes (Partial Response) TYMS, TSER2/3 (G)	2 participants
Genetic Polymorphisms That May Alter Treatment Outcomes (Partial Response) TYMS, TSER2/3 (C)	2 participants

SECONDARY outcome

Timeframe: 4 years

Population: 9 out of 25 participants had a partial response.

This outcome looks at what genotypes of the TYMS 3'-UTR 1494delTTAAAG(6 bp) (rs34489327) gene had a partial tumor response.

Outcome measures

Outcome measures
Measure	Oxaliplatin/Leucovorin/5-FU n=9 Participants "Good risk" patients with the TSER\2/\2 or \2/\3 genotype or low TS expression genotype received treatment of oxaliplatin, leucovorin given over 2 hours along with 5-FU given as intravenous push followed by 5-FU given as intravenous infusion of 46 hours. This treatment was repeated every 2 weeks.
Genetic Polymorphisms That May Alter Treatment Outcomes (Partial Response) +6 bp/+6 bp	5 participants
Genetic Polymorphisms That May Alter Treatment Outcomes (Partial Response) +6 bp/-6 bp	4 participants

SECONDARY outcome

Timeframe: 4 years

Population: 9 out of 25 participants had a partial response.

This outcome looks at what genotypes of the ERCC1 c.354C\>T (rs11615) gene had a partial tumor response.

Outcome measures

Outcome measures
Measure	Oxaliplatin/Leucovorin/5-FU n=9 Participants "Good risk" patients with the TSER\2/\2 or \2/\3 genotype or low TS expression genotype received treatment of oxaliplatin, leucovorin given over 2 hours along with 5-FU given as intravenous push followed by 5-FU given as intravenous infusion of 46 hours. This treatment was repeated every 2 weeks.
Genetic Polymorphisms That May Alter Treatment Outcomes (Partial Response) C/C	2 participants
Genetic Polymorphisms That May Alter Treatment Outcomes (Partial Response) C/T	4 participants
Genetic Polymorphisms That May Alter Treatment Outcomes (Partial Response) T/T	3 participants

SECONDARY outcome

Timeframe: 4 years

Population: 9 out of 25 participants had a partial response.

This outcome looks at what genotypes of the ERCC2 c.2251A\>C (rs13181) gene had a partial response.

Outcome measures

Outcome measures
Measure	Oxaliplatin/Leucovorin/5-FU n=9 Participants "Good risk" patients with the TSER\2/\2 or \2/\3 genotype or low TS expression genotype received treatment of oxaliplatin, leucovorin given over 2 hours along with 5-FU given as intravenous push followed by 5-FU given as intravenous infusion of 46 hours. This treatment was repeated every 2 weeks.
Genetic Polymorphisms That May Alter Treatment Outcomes (Partial Response) A/A	5 participants
Genetic Polymorphisms That May Alter Treatment Outcomes (Partial Response) A/C	3 participants
Genetic Polymorphisms That May Alter Treatment Outcomes (Partial Response) C/C	1 participants

SECONDARY outcome

Timeframe: 4 years

Population: 9 out of 25 participants had a partial response.

This outcome looks at what genotypes of the GSTP1 c.313A\>G (rs1695) gene had a partial response.

Outcome measures

Outcome measures
Measure	Oxaliplatin/Leucovorin/5-FU n=9 Participants "Good risk" patients with the TSER\2/\2 or \2/\3 genotype or low TS expression genotype received treatment of oxaliplatin, leucovorin given over 2 hours along with 5-FU given as intravenous push followed by 5-FU given as intravenous infusion of 46 hours. This treatment was repeated every 2 weeks.
Genetic Polymorphisms That May Alter Treatment Outcomes (Partial Response) A/A	4 participants
Genetic Polymorphisms That May Alter Treatment Outcomes (Partial Response) A/G	3 participants
Genetic Polymorphisms That May Alter Treatment Outcomes (Partial Response) G/G	2 participants

SECONDARY outcome

Timeframe: 4 years

Population: 9 out of 25 participants had a partial response.

This outcome looks at what genotypes of the XRCC1 c.1196G\>A (rs25487) gene had a partial response.

Outcome measures

Outcome measures
Measure	Oxaliplatin/Leucovorin/5-FU n=9 Participants "Good risk" patients with the TSER\2/\2 or \2/\3 genotype or low TS expression genotype received treatment of oxaliplatin, leucovorin given over 2 hours along with 5-FU given as intravenous push followed by 5-FU given as intravenous infusion of 46 hours. This treatment was repeated every 2 weeks.
Genetic Polymorphisms That May Alter Treatment Outcomes (Partial Response) A/A	1 participants
Genetic Polymorphisms That May Alter Treatment Outcomes (Partial Response) G/A	6 participants
Genetic Polymorphisms That May Alter Treatment Outcomes (Partial Response) G/G	2 participants

SECONDARY outcome

Timeframe: 4 years

Population: 9 out of 25 participants had a partial response.

This outcome looks at what genotypes of the MDR1 c.3435C\>T (rs1045642) gene had a partial response.