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

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01260194
First received: December 13, 2010
Last updated: August 1, 2016
Last verified: August 2016
  Purpose
This open-label, multi-center study will evaluate the efficacy and safety of Herceptin (trastuzumab) in combination with standard chemotherapy as first-line treatment in patients with HER2 positive metastatic adenocarcinoma of the stomach or gastro-esophageal junction. Patients will receive standard chemotherapy for a maximum of 6 cycles, and 8 mg/kg Herceptin as loading dose on day 1, followed by 6 mg/kg intravenous infusion every 3 weeks until disease progression.

Condition Intervention Phase
Gastric Cancer
Drug: trastuzumab [Herceptin]
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-label, Multicentre Phase IV Study of Trastuzumab in Combination With the Standard Therapy (as Per Routine Clinical Practice) as First-line Therapy in Patients With HER2 Positive Metastatic Gastric Cancer

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Median Progression Free Survival (PFS) [ Time Frame: Baseline up to PD or death (maximum up to 22 months) ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Overall Survival (OS) [ Time Frame: Baseline up to death (maximum up to 22 months) ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Overall Tumor Response [ Time Frame: Baseline up to PD or death (maximum up to 22 months) ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Clinical Benefit Response (CBR) [ Time Frame: Baseline up to PD or death (maximum up to 22 months) ] [ Designated as safety issue: No ]
    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.

  • Duration of Response (DR) [ Time Frame: Baseline up to PD or death (maximum up to 22 months) ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) [ Time Frame: Baseline up to 6 month after last dose of study drug (maximum up to 22 months) ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters [ Time Frame: Baseline up to 6 month after last dose of study drug (maximum up to 22 months) ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With Clinically Significant Change From Baseline in Left Ventricular Ejection Fraction (LVEF) [ Time Frame: Baseline, thereafter every 12 weeks (maximum up to 22 months) ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With Human Epidermal Growth Factor Receptor 2 (HER2) Positive Gastric Cancer [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    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.


Enrollment: 4
Study Start Date: June 2011
Study Completion Date: January 2015
Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: trastuzumab [Herceptin]
Loading dose of 8 mg/kg on day 1, followed by 6 mg/kg intravenous infusion every 3 weeks until disease progression in combination with standard chemotherapy

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adult patients, >/=18 years of age
  • Histologically confirmed adenocarcinoma of the stomach or gastro-esophageal junction with advanced or metastatic disease, not amenable to curative therapy
  • Measurable disease, according to the Response Evaluation Criteria in Solid Tumors (RECIST)
  • HER2 positive tumor (primary tumor or metastasis
  • ECOG Performance status 0, 1 or 2
  • Life expectancy of at least 3 months

Exclusion Criteria:

  • Previous chemotherapy for advanced or metastatic disease less than 6 month before study start
  • Lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome (patients with partial or total gastrectomy are allowed to participate in the study)
  • Patients with active (significant or uncontrolled) gastrointestinal bleeding
  • Residual relevant toxicity resulting from previous chemotherapy
  • Other malignancy within the last 5 years (except carcinoma in situ of the cervix, or basal cell carcinoma)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01260194

Locations
India
New Delhi, Delhi, India, 110085
Bangalore, Karnataka, India, 560027
Bangalore, India, 560029
Nagpur, India, 440012
Noida, India, 201 301
Vishakpatnam, India, 530002
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01260194     History of Changes
Other Study ID Numbers: ML25477 
Study First Received: December 13, 2010
Results First Received: February 15, 2016
Last Updated: August 1, 2016
Health Authority: India: Drug Controller General

Additional relevant MeSH terms:
Stomach Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Trastuzumab
Antineoplastic Agents

ClinicalTrials.gov processed this record on September 26, 2016