Trial Outcomes & Findings for A Study of Herceptin (Trastuzumab) in Combination With Standard Chemotherapy in Patients With HER Positive Metastatic Gastric Cancer (NCT NCT01260194)

NCT ID: NCT01260194

Last Updated: 2016-11-02

Results Overview

The PFS was defined as the median time between the day of enrollment and the first documentation of progressive disease (PD) or date of death, whichever occurred first. PD was defined as at least 20 percent (%) increase (including an absolute increase of at least 5 millimeters \[mm\]) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. The censoring date was the last date of "last tumor measurement," "last date of study drug treatment," or "last follow-up." The median PFS time with 95% confidence interval (CI) was estimated using Kaplan Meier method.

• Recruitment status: TERMINATED
• Study phase: PHASE4
• Target enrollment: 4 participants
• Primary outcome timeframe: Baseline up to PD or death (maximum up to 22 months)
• Results posted on: 2016-11-02

Participant Flow

Participant milestones

Measure	Trastuzumab Trastuzumab was administered at a loading dose of 8 milligram per kilogram (mg/kg) body weight on Day 1, followed by 6 mg/kg intravenous infusion every 3 weeks plus standard chemotherapy as per Investigator's discretion or as per institutional practice, until disease progression, early withdrawal due to unmanageable toxicity, or consent withdrawal.
Overall Study STARTED	4
Overall Study COMPLETED	3
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Measure	Trastuzumab Trastuzumab was administered at a loading dose of 8 milligram per kilogram (mg/kg) body weight on Day 1, followed by 6 mg/kg intravenous infusion every 3 weeks plus standard chemotherapy as per Investigator's discretion or as per institutional practice, until disease progression, early withdrawal due to unmanageable toxicity, or consent withdrawal.
Overall Study Withdrawal of Consent	1

Baseline Characteristics

A Study of Herceptin (Trastuzumab) in Combination With Standard Chemotherapy in Patients With HER Positive Metastatic Gastric Cancer

Baseline characteristics by cohort

Measure	Trastuzumab n=4 Participants Trastuzumab was administered at a loading dose of 8 mg/kg on Day 1, followed by 6 mg/kg intravenous infusion every 3 weeks plus standard chemotherapy as per Investigator's discretion or as per institutional practice, until disease progression, early withdrawal due to unmanageable toxicity, or consent withdrawal.
Age, Continuous	64.8 years STANDARD_DEVIATION 7.27 • n=5 Participants
Gender Female	1 Participants n=5 Participants
Gender Male	3 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline up to PD or death (maximum up to 22 months)

Population: ITT population.

The PFS was defined as the median time between the day of enrollment and the first documentation of progressive disease (PD) or date of death, whichever occurred first. PD was defined as at least 20 percent (%) increase (including an absolute increase of at least 5 millimeters [mm]) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. The censoring date was the last date of "last tumor measurement," "last date of study drug treatment," or "last follow-up." The median PFS time with 95% confidence interval (CI) was estimated using Kaplan Meier method.

Outcome measures

Measure	Trastuzumab n=4 Participants Trastuzumab was administered at a loading dose of 8 mg/kg on Day 1, followed by 6 mg/kg intravenous infusion every 3 weeks plus standard chemotherapy as per Investigator's discretion or as per institutional practice, until disease progression, early withdrawal due to unmanageable toxicity, or consent withdrawal.
Median Progression Free Survival (PFS)	254.0 days Interval 52.0 to 508.0

SECONDARY outcome

Timeframe: Baseline up to death (maximum up to 22 months)

Population: ITT population.

OS was defined as the time from the date of enrollment to the date of the death (from any cause). If no death was observed, censored observations were taken into account in the analysis. The censoring date was the last date of "last tumor measurement," "last date in drug log," or "last follow-up." The median overall survival time with 95% CI was estimated using Kaplan Meier method.

Outcome measures

Measure	Trastuzumab n=4 Participants Trastuzumab was administered at a loading dose of 8 mg/kg on Day 1, followed by 6 mg/kg intravenous infusion every 3 weeks plus standard chemotherapy as per Investigator's discretion or as per institutional practice, until disease progression, early withdrawal due to unmanageable toxicity, or consent withdrawal.
Overall Survival (OS)	508.0 days Interval 82.0 to Data could not be estimated due to insufficient number of deaths (less than or equal to \[\<=\] 50% participants).

SECONDARY outcome

Timeframe: Baseline up to PD or death (maximum up to 22 months)

Population: ITT population.

Overall tumor response was defined as the occurrence of either a confirmed complete response (CR) or a partial response (PR) as best overall response as determined by the Response Evaluation Criteria In Solid Tumors (RECIST) criteria version (v) 1.1 from confirmed radio-graphic evaluations of target and non-target lesions. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease; all nodes, both target and non-target, must decrease to normal (short axis less than [<]10 mm); no new lesions. PR was defined as greater than or equal to (>=) 30% decrease under baseline of the sum of diameters of all target lesions (the short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions); no unequivocal progression of non-target disease; no new lesions.

Outcome measures

Measure	Trastuzumab n=4 Participants Trastuzumab was administered at a loading dose of 8 mg/kg on Day 1, followed by 6 mg/kg intravenous infusion every 3 weeks plus standard chemotherapy as per Investigator's discretion or as per institutional practice, until disease progression, early withdrawal due to unmanageable toxicity, or consent withdrawal.
Percentage of Participants With Overall Tumor Response	50 percentage of participants Interval 9.4 to 99.2

SECONDARY outcome

Timeframe: Baseline up to PD or death (maximum up to 22 months)

Population: ITT population.

CBR was defined as any response among stable disease (SD) for 6 weeks or longer, CR, or PR as determined by the RECIST v 1.1. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease; all nodes, both target and non-target, must decrease to normal (short axis <10 mm); no new lesions. PR was defined as >=30% decrease under baseline of the sum of diameters of all target lesions (the short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions); no unequivocal progression of non-target disease; no new lesions. PD was defined as at least 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. SD was defined as not qualifying for CR, PR, or PD.

Outcome measures

Measure	Trastuzumab n=4 Participants Trastuzumab was administered at a loading dose of 8 mg/kg on Day 1, followed by 6 mg/kg intravenous infusion every 3 weeks plus standard chemotherapy as per Investigator's discretion or as per institutional practice, until disease progression, early withdrawal due to unmanageable toxicity, or consent withdrawal.
Percentage of Participants With Clinical Benefit Response (CBR)	75.0 percentage of participants Interval 29.2 to 100.0

SECONDARY outcome

Timeframe: Baseline up to PD or death (maximum up to 22 months)

Population: ITT population. The number of participants analyzed signifies the number of participants analyzed for this outcome measure.

DR was based on RECIST criteria v1.1 and was defined as time from date the CR or PR was first recorded to the date on which PD was first noted. CR: complete disappearance of all target lesions and non-target disease, with the exception of nodal disease; all nodes, both target and non-target, must decrease to normal (short axis <10 mm); no new lesions. PR: >=30% decrease under baseline of the sum of diameters of all target lesions; no unequivocal progression of non-target disease; no new lesions. PD: at least 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions and/or appearance of 1 or more new lesions. For the participants with no documented progression after CR or PR, the censored date (the date of "death," the "last tumor measurement," "last date in drug log," or "last follow-up") was taken into consideration. The median duration of response with 95% CI was estimated using Kaplan Meier method.

Outcome measures

Measure	Trastuzumab n=2 Participants Trastuzumab was administered at a loading dose of 8 mg/kg on Day 1, followed by 6 mg/kg intravenous infusion every 3 weeks plus standard chemotherapy as per Investigator's discretion or as per institutional practice, until disease progression, early withdrawal due to unmanageable toxicity, or consent withdrawal.
Duration of Response (DR)	NA days Data could not be estimated because disease progression was not documented.

SECONDARY outcome

Timeframe: Baseline up to 6 month after last dose of study drug (maximum up to 22 months)

Population: Safety population included all participants who had received at least 1 dose of study drug.

An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in participant hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both serious and non-serious AEs.

Outcome measures

Measure	Trastuzumab n=4 Participants Trastuzumab was administered at a loading dose of 8 mg/kg on Day 1, followed by 6 mg/kg intravenous infusion every 3 weeks plus standard chemotherapy as per Investigator's discretion or as per institutional practice, until disease progression, early withdrawal due to unmanageable toxicity, or consent withdrawal.
Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) AEs	4 participants
Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) SAEs	2 participants

SECONDARY outcome

Timeframe: Baseline up to 6 month after last dose of study drug (maximum up to 22 months)

Population: Safety population.

Lab parameters assessed during the study were serum chemistry, biochemistry - serum electrolytes, hematology, 12 lead electrocardiogram, and urinalysis - protein, glucose, blood and other lab tests. Laboratory tests were graded according to the National Cancer Institute-Common Toxicity Criteria (NCI-CTC) version 3.

Outcome measures

Measure	Trastuzumab n=4 Participants Trastuzumab was administered at a loading dose of 8 mg/kg on Day 1, followed by 6 mg/kg intravenous infusion every 3 weeks plus standard chemotherapy as per Investigator's discretion or as per institutional practice, until disease progression, early withdrawal due to unmanageable toxicity, or consent withdrawal.
Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters	0 participants

SECONDARY outcome

Timeframe: Baseline, thereafter every 12 weeks (maximum up to 22 months)

Population: Safety population.

The LVEF was measured using Multi Gated Acquisition (MUGA) or echocardiography (echocardiography was preferred), using the same technique throughout for consistency in an individual participant. Baseline LVEF assessments were done within 21 days prior to the start of treatment. Participants with clinically significant change from baseline (that is, absolute drop in LVEF of >=15%, and drop to a value <50%) have been reported.

Outcome measures

Measure	Trastuzumab n=4 Participants Trastuzumab was administered at a loading dose of 8 mg/kg on Day 1, followed by 6 mg/kg intravenous infusion every 3 weeks plus standard chemotherapy as per Investigator's discretion or as per institutional practice, until disease progression, early withdrawal due to unmanageable toxicity, or consent withdrawal.
Number of Participants With Clinically Significant Change From Baseline in Left Ventricular Ejection Fraction (LVEF)	0 participants

SECONDARY outcome

Timeframe: Baseline

Population: Safety population.

The HER2 status was determination by using immunohistochemistry (IHC) and confirmatory Fluorescent In Situ Hybridization (FISH) techniques. Only participants with HER2 positivity were allowed to receive study medication.

Outcome measures

Measure	Trastuzumab n=4 Participants Trastuzumab was administered at a loading dose of 8 mg/kg on Day 1, followed by 6 mg/kg intravenous infusion every 3 weeks plus standard chemotherapy as per Investigator's discretion or as per institutional practice, until disease progression, early withdrawal due to unmanageable toxicity, or consent withdrawal.
Number of Participants With Human Epidermal Growth Factor Receptor 2 (HER2) Positive Gastric Cancer	4 participants

Adverse Events

Trastuzumab

Serious events: 2 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Measure	Trastuzumab n=4 participants at risk Trastuzumab was administered at a loading dose of 8 mg/kg on Day 1, followed by 6 mg/kg intravenous infusion every 3 weeks plus standard chemotherapy as per Investigator's discretion or as per institutional practice, until disease progression, early withdrawal due to unmanageable toxicity, or consent withdrawal.
Blood and lymphatic system disorders Anaemia	25.0% 1/4 • 22 months
Blood and lymphatic system disorders Deep vein thrombosis	25.0% 1/4 • 22 months
Gastrointestinal disorders Diarrhoea	25.0% 1/4 • 22 months
Respiratory, thoracic and mediastinal disorders Dyspnoea	25.0% 1/4 • 22 months
General disorders Fatigue	25.0% 1/4 • 22 months
Infections and infestations Gastroenteritis	25.0% 1/4 • 22 months
Gastrointestinal disorders Melaena	25.0% 1/4 • 22 months
Infections and infestations Pulmonary tuberculosis	25.0% 1/4 • 22 months
Gastrointestinal disorders Vomiting	25.0% 1/4 • 22 months

Other adverse events

Measure	Trastuzumab n=4 participants at risk Trastuzumab was administered at a loading dose of 8 mg/kg on Day 1, followed by 6 mg/kg intravenous infusion every 3 weeks plus standard chemotherapy as per Investigator's discretion or as per institutional practice, until disease progression, early withdrawal due to unmanageable toxicity, or consent withdrawal.
Gastrointestinal disorders Diarrhoea	25.0% 1/4 • 22 months
Gastrointestinal disorders Mouth ulceration	25.0% 1/4 • 22 months
General disorders Fatigue	25.0% 1/4 • 22 months
General disorders Pyrexia	25.0% 1/4 • 22 months
Hepatobiliary disorders Jaundice cholestatic	25.0% 1/4 • 22 months
Infections and infestations Furuncle	25.0% 1/4 • 22 months
Investigations Blood creatinine increased	25.0% 1/4 • 22 months
Investigations Neutrophil count decreased	25.0% 1/4 • 22 months
Nervous system disorders Neuropathy peripheral	25.0% 1/4 • 22 months
Nervous system disorders Paraesthesia	25.0% 1/4 • 22 months
Nervous system disorders Peripheral sensory neuropathy	25.0% 1/4 • 22 months

Additional Information

Medical Communications

Hoffmann-LaRoche

Phone: 800-821-8590

Email: genentech@druginfo.com

Results disclosure agreements

• Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
• Publication restrictions are in place

Restriction type: OTHER