A Continuation Study of Herceptin (Trastuzumab) in Participants With Metastatic or Locally Advanced Cancer

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02721641
• Collaborator: (none)
• Enrollment: 69
• Locations: 41
• Arm: 1
• Duration (Months): 188.1
• Patients Per Site: 1.7
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This study is designed to provide continued access to intravenous (IV) Herceptin and to evaluate long-term outcomes and overall safety in participants with stable disease and human epidermal growth factor 2 (HER2)-overexpressing metastatic or locally advanced cancer who have completed a prior study with IV Herceptin.

Condition or Disease	Intervention/Treatment	Phase
Neoplasms	Drug: Herceptin	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 69 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Single Arm, Multi-Center, International, Continuation Trial of Recombinant Humanized Antibody Herceptin (Trastuzumab) in Patients With HER2-Overexpressing Tumors
• Study Start Date: Jun 1, 1999
• Actual Primary Completion Date: Feb 1, 2015
• Actual Study Completion Date: Feb 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Herceptin Participants with stable disease and HER2-overexpressing metastatic or locally advanced cancer will receive expanded access to IV Herceptin until disease progression, unacceptable toxicity, death, or decision by the investigator or participant to discontinue treatment.	Drug: Herceptin; Herceptin will be administered as either 2 milligrams per kilogram (mg/kg) once weekly (first dose as a 4-mg/kg loading dose) or 6 mg/kg every 3 weeks (first dose as an 8-mg/kg loading dose) via IV infusion over 90 minutes.; Other Names: Trastuzumab

Outcome Measures

Primary Outcome Measures

1. On-Study Duration of Trial Treatment [From date of enrollment until death or premature withdrawal (maximum 7.4 years of follow-up)]

2. Number of Participants With Drop in Left Ventricular Ejection Fraction (LVEF) Below 45 Percent (%) [From date of enrollment until disease progression, death, or premature withdrawal; assessed per investigator discretion (maximum 7.4 years of follow-up)]

3. Number of Participants Withdrawn From Study Because of LVEF Dysfunction [From date of enrollment until death or premature withdrawal (maximum 7.4 years of follow-up)]

   LVEF dysfunction was defined as low LVEF measured on two consecutive assessments, with the second assessment performed after 3 weeks of study medication being withheld. Low LVEF included values less than or equal to 39% or values between 40% and 45% (inclusive) with a decrease of 10 or more percentage points from Baseline.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Ongoing participants from any completed global Roche-sponsored Herceptin trial

• Participants enrolled in any Roche-sponsored Herceptin trial who have at least stable disease (or whose disease has not recurred) during Herceptin therapy at the end of the lead-in trial

• Available study termination data (including tumor assessment and laboratory data) on the Case Report Form for the lead-in trial

• Judged eligible by the investigator following a thorough risk/benefit assessment, if signs of chronic heart failure developed during the lead-in trial

Exclusion Criteria:

• Pregnant or nursing women

• Women of childbearing potential unless using effective contraception as determined by the investigator

• Severe dyspnea at rest requiring supplementary oxygen therapy

• Severe uncontrolled systemic disease

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Liverpool	New South Wales	Australia	2170
2		Waratah	New South Wales	Australia	2298
3		Brisbane	Queensland	Australia	4006
4		Brisbane	Queensland	Australia	4066
5		Fitzroy	Victoria	Australia	3065
6		Geelong	Victoria	Australia	3220
7		Parkville	Victoria	Australia	3052
8		Brussel		Belgium	1090
9		Beijing		China	100021
10		Beijing		China	100142
11		Marseille		France	13273
12		Berlin		Germany	12203
13		Göttingen		Germany	37075
14		Hamburg		Germany	20246
15		Heidelberg		Germany	69120
16		Lübeck		Germany	23538
17		Muenchen		Germany	80637
18		Muenchen		Germany	81377
19		Trier		Germany	54290
20		Guatemala City		Guatemala	01010
21		Budapest		Hungary	1122
22		Debrecen		Hungary	4032
23		Ramat Gan		Israel	5262100
24		Bundang City		Korea, Republic of	463-802
25		Seoul		Korea, Republic of	03080
26		Seoul		Korea, Republic of	120-752
27		Seoul		Korea, Republic of	138-736
28		Auckland		New Zealand	1023
29		Panama City		Panama	0832-00752
30		Gdansk		Poland	80-214
31		Lisboa		Portugal	1099-023
32		Izhevsk		Russian Federation	426009
33		Moscow		Russian Federation	115478
34		Saint-Petersburg		Russian Federation	197758
35		Belgrade		Serbia	11000
36		Alicante		Spain	3010
37		Barcelona		Spain	08035
38		Edinburgh		United Kingdom	EH4 2XU
39		Glasgow		United Kingdom	G12 0YN
40		London		United Kingdom	SE1 9RT
41		Nottingham		United Kingdom	NG5 1PB

Sponsors and Collaborators

• Hoffmann-La Roche

Investigators

• Study Chair: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT02721641
• Other Study ID Numbers: BO15943; 2007-000348-28
• First Posted: Mar 29, 2016
• Last Update Posted: Mar 31, 2017
• Last Verified: Feb 1, 2017

• Additional relevant MeSH terms: Trastuzumab

Study Results

Participant Flow

Arm/Group Title	Herceptin
Arm/Group Description	Participants received intravenous (IV) Herceptin until disease progression, unacceptable toxicity, death, or decision by the investigator or participant to discontinue treatment. Herceptin was administered at the discretion of the investigator as either 2 milligrams per kilogram (mg/kg) once weekly (first dose as a 4-mg/kg loading dose) or 6 mg/kg every 3 weeks (first dose as an 8-mg/kg loading dose) via IV infusion over 90 minutes.
Period Title: Overall Study
STARTED	69
COMPLETED	69
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Herceptin
Arm/Group Description	Participants received IV Herceptin until disease progression, unacceptable toxicity, death, or decision by the investigator or participant to discontinue treatment. Herceptin was administered at the discretion of the investigator as either 2 mg/kg once weekly (first dose as a 4-mg/kg loading dose) or 6 mg/kg every 3 weeks (first dose as an 8-mg/kg loading dose) via IV infusion over 90 minutes.
Overall Participants	69
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58.0 (11.00)
Sex/Gender, Customized (participants) [Number]

Outcome Measures

1. Primary Outcome

Title	On-Study Duration of Trial Treatment
Time Frame	From date of enrollment until death or premature withdrawal (maximum 7.4 years of follow-up)

Outcome Measure Data

Analysis Population Description

Analysis was performed on all enrolled participants.

Arm/Group Title	Herceptin
Arm/Group Description	Participants received IV Herceptin until disease progression, unacceptable toxicity, death, or decision by the investigator or participant to discontinue treatment. Herceptin was administered at the discretion of the investigator as either 2 mg/kg once weekly (first dose as a 4-mg/kg loading dose) or 6 mg/kg every 3 weeks (first dose as an 8-mg/kg loading dose) via IV infusion over 90 minutes.
Measure Participants	69
Median (Full Range) [days]	386.0

2. Primary Outcome

Title	Number of Participants With Drop in Left Ventricular Ejection Fraction (LVEF) Below 45 Percent (%)
Time Frame	From date of enrollment until disease progression, death, or premature withdrawal; assessed per investigator discretion (maximum 7.4 years of follow-up)

Outcome Measure Data

Analysis Population Description

All enrolled participants with available LVEF data were included in the analysis.

Arm/Group Title	Herceptin
Arm/Group Description	Participants received IV Herceptin until disease progression, unacceptable toxicity, death, or decision by the investigator or participant to discontinue treatment. Herceptin was administered at the discretion of the investigator as either 2 mg/kg once weekly (first dose as a 4-mg/kg loading dose) or 6 mg/kg every 3 weeks (first dose as an 8-mg/kg loading dose) via IV infusion over 90 minutes.
Measure Participants	26
Count of Participants [Participants]	0 0%

3. Primary Outcome

Title	Number of Participants Withdrawn From Study Because of LVEF Dysfunction
Description	LVEF dysfunction was defined as low LVEF measured on two consecutive assessments, with the second assessment performed after 3 weeks of study medication being withheld. Low LVEF included values less than or equal to 39% or values between 40% and 45% (inclusive) with a decrease of 10 or more percentage points from Baseline.
Time Frame	From date of enrollment until death or premature withdrawal (maximum 7.4 years of follow-up)

Outcome Measure Data

Analysis Population Description

All enrolled participants with available LVEF data were included in the analysis.

Arm/Group Title	Herceptin
Arm/Group Description	Participants received IV Herceptin until disease progression, unacceptable toxicity, death, or decision by the investigator or participant to discontinue treatment. Herceptin was administered at the discretion of the investigator as either 2 mg/kg once weekly (first dose as a 4-mg/kg loading dose) or 6 mg/kg every 3 weeks (first dose as an 8-mg/kg loading dose) via IV infusion over 90 minutes.
Measure Participants	26
Count of Participants [Participants]	0 0%

Adverse Events

Time Frame	From date of enrollment until disease progression, unacceptable toxicity, death, or decision by the investigator or participant to discontinue treatment (up to approximately 7.4 years)
Adverse Event Reporting Description	Only serious adverse events were collected during the trial. Terms were reported verbatim as provided by the reporter and were not re-coded. Analysis was performed on all enrolled participants.
Arm/Group Title	Herceptin
Arm/Group Description	Participants received IV Herceptin until disease progression, unacceptable toxicity, death, or decision by the investigator or participant to discontinue treatment. Herceptin was administered at the discretion of the investigator as either 2 mg/kg once weekly (first dose as a 4-mg/kg loading dose) or 6 mg/kg every 3 weeks (first dose as an 8-mg/kg loading dose) via IV infusion over 90 minutes.
All Cause Mortality
	Herceptin
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Herceptin
	Affected / at Risk (%)	# Events
Total	11/69 (15.9%)
Gastrointestinal disorders
Nausea	1/69 (1.4%)
Upper gastrointestinal haemorrhage	1/69 (1.4%)
Vomiting	1/69 (1.4%)
General disorders
Pain	1/69 (1.4%)
Infections and infestations
Arthritis bacterial	1/69 (1.4%)
Erysipelas	1/69 (1.4%)
Urinary tract infection	1/69 (1.4%)
Injury, poisoning and procedural complications
Fibula fracture	1/69 (1.4%)
Lower limb fracture	1/69 (1.4%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm malignant	1/69 (1.4%)
Nervous system disorders
Headache	1/69 (1.4%)
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	1/69 (1.4%)
Surgical and medical procedures
Pain management	1/69 (1.4%)
Other (Not Including Serious) Adverse Events
	Herceptin
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.