Breast CancerPhase 1/2NCT00033514

Trastuzumab and Erlotinib as First-Line Therapy in Treating Women With Metastatic Breast Cancer Associated With HER2/Neu Overexpression

A Phase 1/2 study testing trastuzumab and erlotinib hydrochloride in people with Breast Cancer, run by Jonsson Comprehensive Cancer Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

RATIONALE: Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Biological therapies such as erlotinib may interfere with the growth of tumor cells and slow the growth of the tumor. Read more about this study

Who is it for?: Ages 18 years and older, women only
Conditions the study is for: Breast Cancer
What is being tested?: trastuzumab and erlotinib hydrochloride
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 27 participants
Where: 1 siteUnited States
Study dates: Aug 2001to Dec 2011
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
Women only
No healthy volunteers
Adult, Older adult

Who may be able to join

Women aged > 18 years
Histologically documents metastatic breast cancer
HER2 positive using Fluorescence In Situ Hybridization (FISH)
For phase I, patients who have previously received treatment for their metastatic disease are allowed to participate.
For the phase II portion of the study, patients must have measureable disease (> 2 cm; > 1 cm on spiral CT scan)
Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
A life expectancy of > 3 months
Use of effective means of contraception

Who cannot join

For Phase II, prior cytotoxic chemotherapy and/or prior Herceptin for their metastatic disease. Prior treatment in the adjuvant setting is allowed.

Trial locations and contacts

1 site in 1 country.

United States1 site

Jonsson Comprehensive Cancer Center at UCLA
Los Angeles, California, 90095-1781

Other trials in United States

About this study

Official title: Phase I/II Study Of Herceptin Combined With OSI-774 In The First-Line Treatment Of Metastatic Breast Cancer Associated With HER2/Neu Overexpression

PURPOSE: Phase II trial to study the effectiveness of combining trastuzumab with erlotinib as first-line therapy in treating women who have metastatic breast cancer associated with HER2/neu overexpression.

Read the detailed description

OBJECTIVES:

Determine the maximum tolerated dose and recommended phase II dose of erlotinib when combined with trastuzumab (Herceptin) as first-line therapy in women with metastatic breast cancer associated with HER2/neu overexpression. (Phase I closed to accrual as of 01/2004)
Determine the safety profile of this regimen in these patients.
Determine the rate and duration of objective response in patients treated with this regimen.
Determine the pharmacologic behavior of this regimen in these patients.
Determine time to disease progression and duration of survival in patients treated with this regimen.
Correlate the antitumor activity of this regimen with epidermal growth factor receptor expression in these patients.

OUTLINE: This is a dose-escalation study of erlotinib. (Phase I closed to accrual as of 01/2004).

Patients receive oral erlotinib once daily beginning on day 2 and trastuzumab (Herceptin) IV over 30-90 minutes (1-4 hours after erlotinib) once weekly beginning on day 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, additional patients are treated at the recommended phase II dose.

Patients are followed every 2 months.

PROJECTED ACCRUAL: A total of 3-18 patients will be accrued for the phase I portion (closed to accrual as of 01/2004) and 27-81 patients will be accrued for the phase II portion of this study.

Conditions: Breast Cancer
Being tested: trastuzumab, erlotinib hydrochloride
Keywords: stage IV breast cancer, recurrent breast cancer
Medical subject headings: Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

trastuzumabBiological
Also called Herceptin
Day 1 4mg/kg IV 2 mg/kg IV weekly.
erlotinib hydrochlorideDrug
Also called OSI-774
100 mg daily on Course 1 Day 2. After three weeks patients who have not experienced specific adverse events, dose will be escalated to 150 mg daily. Patients who have experienced specific adverse events dose will remain 100 mg daily or dose reduced as necessary per protocol.

Study groups in NCT00033514
Study group	Role	What they receive
treatment	Experimental	please see intervention description Receives: Biological: trastuzumab; Drug: erlotinib hydrochloride

What is being measured

The primary outcome is the main question the study is designed to answer.

The Objective Response Rate as Defined as Stable Disease or the Rate of Complete and Partial Responses Determined on Two Consecutive Occasions Greater Than or Equal to 4 Weeks Apart.
Complete Response:
The disappearance of all signs of cancer in response to treatment. This does not always mean the cancer has been cured. Also called complete remission.
Partial Response:
A decrease in the size of a tumor, or in the extent of cancer in the body, in response to treatment. Also called partial remission.
Measured: 5 years
Recommended Dose for Phase II
Measured: treatment period

Secondary outcomes (3)

Duration of Objective Response
Measured: 5 years
Incidence of Adverse Events
Measured: 5 years
Serum Concentration of Herceptin at Specified Time-points.
Measured: 4 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Aug 2001Dec 2011

First posted27 Jan 2003 (estimated)
Study startAug 2001
Primary completionDec 2011
Study completionDec 2011

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Breast CancerStudies of the same condition, open and under way.
More trials run by Jonsson Comprehensive Cancer CenterThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 27 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00033514
Sponsor's protocol ID: 01-06-020
Other IDs: CDR0000069295, GENENTECH-OSI2365s, NCI-G02-2057
Status last verified: Feb 2016
First submitted: 9 Apr 2002
Last updated: 8 Oct 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Britten CD, Finn RS, Bosserman LD, Wong SG, Press MF, Malik M, Lum BL, Slamon DJ. A phase I/II trial of trastuzumab plus erlotinib in metastatic HER2-positive breast cancer: a dual ErbB targeted approach. Clin Breast Cancer. 2009 Feb;9(1):16-22. doi: 10.3816/CBC.2009.n.003.
PubMed 19299235

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
RecruitingPhase 2
Gene Signatures to Guide HR+MBC Therapy in a Diverse Cohort
Invasive Mammary Carcinoma, Metastatic Breast Cancer
Not yet recruitingObservational study
Comparison of Reliability, Time Cost, and Participant Comfort of Lymphedema Assessments in Upper Extremity
Lymphedema, Upper Extremity Lymphedema
RecruitingPhase 3
A Study of Camrelizumab Plus Chemotherapy in Combination With or Without Famitinib as Neoadjuvant Therapy in Participants With Triple Negative Breast Cancer (BCTOP-T-N01)
TNBC - Triple-Negative Breast Cancer
RecruitingPhase 3
Testing Whether Hormone Therapy With Ribociclib is as Effective as Chemotherapy Followed by Hormone Therapy With Ribociclib for the Treatment of High Anatomic Stage Breast Cancer With Low Recurrence Risk, The RxFINE-Low Trial
Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8

All Breast Cancer trials

Study at a glance

From the registry record, last updated by the sponsor on 8 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase I/II Study Of Herceptin Combined With OSI-774 In The First-Line Treatment Of Metastatic Breast Cancer Associated With HER2/Neu Overexpression
ClinicalTrials.gov ID: NCT00033514
Acronym / sponsor ID: 01-06-020
Conditions: Breast Cancer
Keywords: stage IV breast cancer, recurrent breast cancer
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 27 participants (actual)
Lead sponsor: Jonsson Comprehensive Cancer CenterUniversity, hospital or other
Collaborators: Genentech, Inc.
Study start: Aug 2001
Primary completion: Dec 2011 (actual)
Study completion: Dec 2011 (actual)
First posted: 27 Jan 2003 (estimated)
Results: Posted 11 Apr 2016

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

OBJECTIVES:

Determine the maximum tolerated dose and recommended phase II dose of erlotinib when combined with trastuzumab (Herceptin) as first-line therapy in women with metastatic breast cancer associated with HER2/neu overexpression. (Phase I closed to accrual as of 01/2004)
Determine the safety profile of this regimen in these patients.
Determine the rate and duration of objective response in patients treated with this regimen.
Determine the pharmacologic behavior of this regimen in these patients.
Determine time to disease progression and duration of survival in patients treated with this regimen.
Correlate the antitumor activity of this regimen with epidermal growth factor receptor expression in these patients.

OUTLINE: This is a dose-escalation study of erlotinib. (Phase I closed to accrual as of 01/2004).

Patients are followed every 2 months.

PROJECTED ACCRUAL: A total of 3-18 patients will be accrued for the phase I portion (closed to accrual as of 01/2004) and 27-81 patients will be accrued for the phase II portion of this study.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
treatment	Experimental	Biological: trastuzumab, Drug: erlotinib hydrochlorideplease see intervention description

Who may qualify

Ages: 18 years and older
Sex: Female only
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (8 listed)

Women aged > 18 years
Histologically documents metastatic breast cancer
HER2 positive using Fluorescence In Situ Hybridization (FISH)
For phase I, patients who have previously received treatment for their metastatic disease are allowed to participate.
For the phase II portion of the study, patients must have measureable disease (> 2 cm; > 1 cm on spiral CT scan)

Key exclusion criteria (1 listed)

For Phase II, prior cytotoxic chemotherapy and/or prior Herceptin for their metastatic disease. Prior treatment in the adjuvant setting is allowed.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
trastuzumabAlso: HerceptinDay 1 4mg/kg IV 2 mg/kg IV weekly.	Biological	treatment
erlotinib hydrochlorideAlso: OSI-774100 mg daily on Course 1 Day 2. After three weeks patients who have not experienced specific adverse events, dose will be escalated to 150 mg daily. Patients who have experienced specific adverse events dose will remain 100 mg daily or dose reduced as necessary per protocol.	Drug	treatment

Primary outcome

The Objective Response Rate as Defined as Stable Disease or the Rate of Complete and Partial Responses Determined on Two Consecutive Occasions Greater Than or Equal to 4 Weeks Apart.
Time frame: 5 years
Complete Response: The disappearance of all signs of cancer in response to treatment. This does not always mean the cancer has been cured. Also called complete remission. Partial Response: A decrease in the size of a tumor, or in the extent of cancer in the body, in response to treatment. Also called partial remission.
Recommended Dose for Phase II
Time frame: treatment period

3 secondary outcomes

Duration of Objective Response
Time frame: 5 years
Incidence of Adverse Events
Time frame: 5 years
Serum Concentration of Herceptin at Specified Time-points.
Time frame: 4 months

Results and safety

Results posted to the registry on 11 Apr 2016, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Treatment Phase 1	16	15
Treatment Phase 2	11	7

Primary outcome: The Objective Response Rate as Defined as Stable Disease or the Rate of Complete and Partial Responses Determined on Two Consecutive Occasions Greater Than or Equal to 4 Weeks Apart.

Time frame: 5 years. Number. Unit: participants

Measure	Treatment Phase 1 Plus Phase 2 n = 12
Partial Response	4
Stable Disease	1

Population analysed: 12 patients with measurable disease and no prior trastuzumab in the metastatic setting considered evaluable at the recommended phase II dose level. 2 from phase 1 and 10 from phase 2 Excluded : 14 from Phase I: no measureable disease or previous trastuzumab. Phase II: Withdrawn due to disease complications

Primary outcome: Recommended Dose for Phase II

Time frame: treatment period. Number. Unit: participants receiving each dose

Measure	Treatment Phase 1 n = 14
50 dose mg/day	6
100 dose mg/day	3
150 dose mg/day	5

Population analysed: patients who have not experienced specific adverse events, dose will be escalated to 150 mg daily. Patients who have experienced specific adverse events dose will remain 100 mg daily or dose reduced as necessary per protocol.

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: 9.4 years. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Treatment Phase 1 Plus Phase 2	16 of 27 (59.3%)	22 of 27 (81.5%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 8 Oct 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 19299235Britten CD, Finn RS, Bosserman LD, Wong SG, Press MF, Malik M, Lum BL, Slamon DJ. A phase I/II trial of trastuzumab plus erlotinib in metastatic HER2-positive breast cancer: a dual ErbB targeted approach. Clin Breast Cancer. 2009 Feb;9(1):16-22. doi: 10.3816/CBC.2009.n.003.

Related trials for Breast Cancer

Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
RecruitingPhase 2
Gene Signatures to Guide HR+MBC Therapy in a Diverse Cohort
Invasive Mammary Carcinoma, Metastatic Breast Cancer
Not yet recruitingObservational study
Comparison of Reliability, Time Cost, and Participant Comfort of Lymphedema Assessments in Upper Extremity
Lymphedema, Upper Extremity Lymphedema
RecruitingPhase 3
A Study of Camrelizumab Plus Chemotherapy in Combination With or Without Famitinib as Neoadjuvant Therapy in Participants With Triple Negative Breast Cancer (BCTOP-T-N01)
TNBC - Triple-Negative Breast Cancer
RecruitingPhase 3
Testing Whether Hormone Therapy With Ribociclib is as Effective as Chemotherapy Followed by Hormone Therapy With Ribociclib for the Treatment of High Anatomic Stage Breast Cancer With Low Recurrence Risk, The RxFINE-Low Trial
Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Carolyn Britten, MD principal investigator

Jonsson Comprehensive Cancer Center

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing trastuzumab and erlotinib hydrochloride in people with Breast Cancer, run by Jonsson Comprehensive Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 11 Apr 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The Objective Response Rate as Defined as Stable Disease or the Rate of Complete and Partial Responses Determined on Two Consecutive Occasions Greater Than or Equal to 4 Weeks Apart. (time frame: 5 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00033514, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Oct 2020.