Metastatic Breast CancerPhase 2NCT00570258

Randomized, Double Blind Multicenter Phase II Study of Time to Progression on Fulvestrant in Combination With Erlotinib or Placebo in Hormone Receptor-Positive Metastatic Breast Cancer (MBC) Subjects Who Progressed on First Line Hormonal Therapy

A Phase 2 study testing Fulvestrant and erlotinib in people with Metastatic Breast Cancer, run by University of Arkansas at 6 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

This is a multicenter, randomized, double-blind study of fulvestrant plus erlotinib versus fulvestrant plus placebo for subjects with metastatic breast cancer whose disease progression after first line hormonal therapy. 1. Read more about this study

Who is it for?: Ages 18 to 55 years, women only
Conditions the study is for: Metastatic Breast Cancer
What is being tested?: Fulvestrant and erlotinib
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 27 participants
Where: 6 sitesUnited States
Study dates: Sep 2006to Dec 2017
Phase: Phase 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 to 55 years
Women only
No healthy volunteers
Adult

Who may be able to join

Subjects must sign a written consent.
Subjects must have estrogen- and/or progesterone-receptor-positive histologically confirmed adenocarcinoma of the breast with recurrent or metastatic carcinoma of the breast.
Baseline measurements and evaluations of involved sites should be performed as close as possible to study entry, but must be within 4 weeks prior to randomization.
Subjects fulfilling one of the following criteria are eligible to participate in the study: Subjects with measurable disease as per RECIST criteria. This is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as over 20 mm with conventional technique or as over 10 mm with spiral CT scan or MRI. Subjects with bone lesions, lytic or mixed (lytic + sclerotic), in the absence of measurable disease as defined by RECIST criteria. The lytic component of at least one bone lesion should measure 20 mm with conventional techniques or 10 mm with spiral CT scan or MRI. At least one bone lesion satisfying these criteria must be outside any previously irradiated area.
All subjects must be postmenopausal females defined by:
Prior bilateral oophorectomy OR No menstrual period for 12 months or longer. If age 55 years or less and on tamoxifen within the prior 6 months, must have an estradiol level in the postmenopausal range.

Who cannot join

1. Subjects must not have had more than 1 prior chemotherapy regimen for metastatic disease and no chemotherapy within 3 weeks prior to randomization. 2. No concurrent chemotherapy is allowed while on protocol therapy. Subjects whose adjuvant hormonal therapy was discontinued more than 12 months ago must have had only 1 prior hormonal therapy for metastatic disease. Subjects who relapsed while receiving adjuvant hormonal therapy or less than 12 months after completing adjuvant hormonal therapy may be enrolled directly in the trial.
3. No prior therapy with an estrogen receptor down-regulator (e.g. fulvestrant). Non-protocol concurrent hormonal therapy is not allowed. Subjects must not have had prior therapy with agents that target EGFR. Previous, but not concomitant, therapy with trastuzumab (Herceptin) is allowed. Subjects must not receive trastuzumab (Herceptin) within 3 weeks prior to randomization.
4. Subjects must have ECOG performance status of 0, 1, or 2. 5. Subjects must have adequate hematologic, hepatic, and renal function defined by the following within 4 weeks prior to randomization: Neutrophils > 1500/mm3 and platelets over 100,000/mm3 Total Bilirubin under 1.25 x Institutional upper limit of normal SGPT (ALT) and SGOT (AST) under 2.5 x Institutional upper limit of normal if no demonstrable liver metastases or under 5 x Institutional upper limit of normal in the presence of liver metastases Calculated creatinine clearance over 30ml/min using the following formula: Ccr = (140 - age in years) times (weight in kgs) times 0.085 72 x serum creatinine in mg/dL INR, PT and PTT under 1.5 x Institutional upper limit of normal.
6. Subjects must not be receiving therapy with anticoagulants or have other contraindication to IM injections.
7. Subjects must be age over 18 years. 8. Subjects must not have a history of central nervous system metastasis. 9. Subjects may receive concurrent radiation therapy to painful sites of bony disease or areas of impending fracture as long as the radiation therapy is initiated prior to study entry and sites of measurable disease outside the radiation therapy port are available to follow.
10. Subjects must not take the following medications while enrolled in this trial: ketoconazole, erythromycin, verapamil.

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11. Subjects age less than 55 years must not be receiving LHRH agonists or antagonists within 3 months prior to randomization.
12. Subjects who have an ocular inflammation or infection should be fully treated before entry into the trial.
13. Subjects with a neuropathic keratopathy or diabetes or those with anterior basement membrane disease must be advised of the need for frequent ophthalmologic exams.
14. Subjects who continue to wear contact lenses must be advised that they have an increased risk of ocular events. The decision to wear contact lenses should be discussed with the patient's treating oncologist and ophthalmologist.
15. Subjects must not suffer from medical or psychiatric conditions that would interfere with protocol compliance, the ability to provide informed consent, or assessment of response or anticipated toxicities.
16. Subjects must be disease-free of prior invasive malignancies for over 5 years with the exception of curatively-treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix.

Trial locations and contacts

6 sites in 1 country.

City, postcode or hospital

6 sites in 1 country

United States6 sites

Emory University
Atlanta, Georgia, 30322
Hackensack University
Hackensack, New Jersey, 07601
NEA Clinic
Jonesboro, Arkansas, 72401
St. Luke's Cancer Institute
Kansas City, Missouri, 64111
University of Arkansas for Medical Sciences
Little Rock, Arkansas, 72205
Highlands oncology Group
Springdale, Arkansas, 72764

Other trials in United States

About this study

To obtain preliminary estimates of the magnitude and variability of the efficacy of fulvestrant in combination with erlotinib in this subject population, and
To obtain historically up-to-date estimates of the magnitude and variability of the efficacy of fulvestrant as the sole active agent in this subject population.

The measure of efficacy for both primary objectives will be time to progression.

Read the detailed description

Total number of subjects planned for the trial is 130 subjects, that is, approximately 65 subjects in each arm.
Subjects will be randomized to receive fulvestrant/erlotinib (arm A) or fulvestrant/placebo (arm B) and stratified based on accrual center.
The study is a parallel-arm double-blind study, with fulvestrant + placebo on the monotherapy arm, and fulvestrant + erlotinib on the combination arm.
The primary variable outcome is time to progression.
Subjects whose metastatic disease was diagnosed more than 12 months after completing adjuvant hormonal therapy are eligible to this study if their breast cancer is hormone-receptor-positive and after disease progression on first line hormonal therapy in the metastatic setting. Subjects may have received no more than one line of chemotherapy. While receiving one line of hormonal therapy in the metastatic setting is a requirement, receiving chemotherapy is not, and one line of chemotherapy in the metastatic setting would not exclude these subjects from the trial. Subjects who had a recurrence while on adjuvant hormonal treatment or within 12 months of completion of the adjuvant hormonal treatment are also eligible without the need to receive first line hormonal therapy in the metastatic setting.

Conditions: Metastatic Breast Cancer
Being tested: Fulvestrant, erlotinib, Placebo
Medical subject headings: Breast Neoplasms

What participants receive

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

FulvestrantDrug
Fulvestrant: 250 mg IM Q 4 weeks
erlotinibDrug
150 mg PO QD
FulvestrantDrug
250 mg IM Q 4 weeks
PlaceboDrug
Placebo 150 mg PO QD

Study groups in NCT00570258
Study group	Role	What they receive
2	Placebo comparator	Fulvestrant: 250 mg IM Q 4 weeks Placebo: 150 mg PO QD Receives: Drug: Fulvestrant; Drug: Placebo
1	Active comparator	Fulvestrant: 250 mg IM Q 4 weeks Erlotinib: 150 mg PO QD Receives: Drug: Fulvestrant; Drug: erlotinib

What is being measured

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

Number of Participants With Progression-free Survival
This will be defined as the date from randomization onset to first documented occurrence of PD. Death will be regarded as a progression event in those subjects who die before disease progression. Subjects without documented objective progression at the time of the final analysis will be censored at the date of their last tumor assessment.
Measured: through study completion, an average of 3 years

Secondary outcomes (1)

Number of Participants Achieving Either Complete Response or Partial Response
evaluate response rate and the clinical benefit of fulvestrant alone or in combination with erlotinib
Measured: through study completion, an average of 3 years

Timeline

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

Sep 2006Dec 2017

First posted10 Dec 2007 (estimated)
Study startSep 2006
Primary completionDec 2010
Study completionDec 2017

Why it stopped: FDA approved higher dose of study drug. Dose used in protocol lower than SOC - enrollment stopped, those on treatment were given option to opt out.

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.
Other trials for Metastatic Breast CancerStudies of the same condition, open and under way.
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 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 27 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00570258
Sponsor's protocol ID: 57485
Other IDs: UARK 2004-19
Status last verified: Mar 2021
First submitted: 6 Dec 2007
Last updated: 30 Mar 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

Study at a glance

From the registry record, last updated by the sponsor on 30 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Randomized, Double Blind Multicenter Phase II Study of Time to Progression on Fulvestrant in Combination With Erlotinib or Placebo in Hormone Receptor-Positive Metastatic Breast Cancer (MBC) Subjects Who Progressed on First Line Hormonal Therapy
ClinicalTrials.gov ID: NCT00570258
Acronym / sponsor ID: 57485
Conditions: Metastatic Breast Cancer
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: FDA approved higher dose of study drug. Dose used in protocol lower than SOC - enrollment stopped, those on treatment were given option to opt out.
Enrolment: 27 participants (actual)
Lead sponsor: University of ArkansasUniversity, hospital or other
Collaborators: OSI Pharmaceuticals
Study start: Sep 2006
Primary completion: Dec 2010 (actual)
Study completion: Dec 2017 (actual)
First posted: 10 Dec 2007 (estimated)
Results: Posted 6 Feb 2019

Clinical summary

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

To obtain preliminary estimates of the magnitude and variability of the efficacy of fulvestrant in combination with erlotinib in this subject population, and
To obtain historically up-to-date estimates of the magnitude and variability of the efficacy of fulvestrant as the sole active agent in this subject population.

The measure of efficacy for both primary objectives will be time to progression.

Detailed description

Total number of subjects planned for the trial is 130 subjects, that is, approximately 65 subjects in each arm.
Subjects will be randomized to receive fulvestrant/erlotinib (arm A) or fulvestrant/placebo (arm B) and stratified based on accrual center.
The study is a parallel-arm double-blind study, with fulvestrant + placebo on the monotherapy arm, and fulvestrant + erlotinib on the combination arm.
The primary variable outcome is time to progression.
Subjects whose metastatic disease was diagnosed more than 12 months after completing adjuvant hormonal therapy are eligible to this study if their breast cancer is hormone-receptor-positive and after disease progression on first line hormonal therapy in the metastatic setting. Subjects may have received no more than one line of chemotherapy. While receiving one line of hormonal therapy in the metastatic setting is a requirement, receiving chemotherapy is not, and one line of chemotherapy in the metastatic setting would not exclude these subjects from the trial. Subjects who had a recurrence while on adjuvant hormonal treatment or within 12 months of completion of the adjuvant hormonal treatment are also eligible without the need to receive first line hormonal therapy in the metastatic setting.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 2

Arm	Type	Receives
2	Placebo comparator	Drug: Fulvestrant, Drug: PlaceboFulvestrant: 250 mg IM Q 4 weeks Placebo: 150 mg PO QD
1	Active comparator	Drug: Fulvestrant, Drug: erlotinibFulvestrant: 250 mg IM Q 4 weeks Erlotinib: 150 mg PO QD

Who may qualify

Ages: 18 to 55 years
Sex: Female only
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (6 listed)

Subjects must sign a written consent.
Subjects must have estrogen- and/or progesterone-receptor-positive histologically confirmed adenocarcinoma of the breast with recurrent or metastatic carcinoma of the breast.
Baseline measurements and evaluations of involved sites should be performed as close as possible to study entry, but must be within 4 weeks prior to randomization.
Subjects fulfilling one of the following criteria are eligible to participate in the study: Subjects with measurable disease as per RECIST criteria. This is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as over 20 mm with conventional technique or as over 10 mm with spiral CT scan or MRI. Subjects with bone lesions, lytic or mixed (lytic + sclerotic), in the absence of measurable disease as defined by RECIST criteria. The lytic component of at least one bone lesion should measure 20 mm with conventional techniques or 10 mm with spiral CT scan or MRI. At least one bone lesion satisfying these criteria must be outside any previously irradiated area.
All subjects must be postmenopausal females defined by:

Key exclusion criteria (12 listed)

1. Subjects must not have had more than 1 prior chemotherapy regimen for metastatic disease and no chemotherapy within 3 weeks prior to randomization. 2. No concurrent chemotherapy is allowed while on protocol therapy. Subjects whose adjuvant hormonal therapy was discontinued more than 12 months ago must have had only 1 prior hormonal therapy for metastatic disease. Subjects who relapsed while receiving adjuvant hormonal therapy or less than 12 months after completing adjuvant hormonal therapy may be enrolled directly in the trial.
3. No prior therapy with an estrogen receptor down-regulator (e.g. fulvestrant). Non-protocol concurrent hormonal therapy is not allowed. Subjects must not have had prior therapy with agents that target EGFR. Previous, but not concomitant, therapy with trastuzumab (Herceptin) is allowed. Subjects must not receive trastuzumab (Herceptin) within 3 weeks prior to randomization.
4. Subjects must have ECOG performance status of 0, 1, or 2. 5. Subjects must have adequate hematologic, hepatic, and renal function defined by the following within 4 weeks prior to randomization: Neutrophils > 1500/mm3 and platelets over 100,000/mm3 Total Bilirubin under 1.25 x Institutional upper limit of normal SGPT (ALT) and SGOT (AST) under 2.5 x Institutional upper limit of normal if no demonstrable liver metastases or under 5 x Institutional upper limit of normal in the presence of liver metastases Calculated creatinine clearance over 30ml/min using the following formula: Ccr = (140 - age in years) times (weight in kgs) times 0.085 72 x serum creatinine in mg/dL INR, PT and PTT under 1.5 x Institutional upper limit of normal.
6. Subjects must not be receiving therapy with anticoagulants or have other contraindication to IM injections.
7. Subjects must be age over 18 years. 8. Subjects must not have a history of central nervous system metastasis. 9. Subjects may receive concurrent radiation therapy to painful sites of bony disease or areas of impending fracture as long as the radiation therapy is initiated prior to study entry and sites of measurable disease outside the radiation therapy port are available to follow.

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
FulvestrantFulvestrant: 250 mg IM Q 4 weeks	Drug	1
erlotinib150 mg PO QD	Drug	1
Fulvestrant250 mg IM Q 4 weeks	Drug	2
PlaceboPlacebo 150 mg PO QD	Drug	2

Primary outcome

Number of Participants With Progression-free Survival
Time frame: through study completion, an average of 3 years
This will be defined as the date from randomization onset to first documented occurrence of PD. Death will be regarded as a progression event in those subjects who die before disease progression. Subjects without documented objective progression at the time of the final analysis will be censored at the date of their last tumor assessment.

1 secondary outcome

Number of Participants Achieving Either Complete Response or Partial Response
Time frame: through study completion, an average of 3 years

Results and safety

Results posted to the registry on 6 Feb 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Fulvestrant Plus Placebo	12	0
Fulvestrant Plus Erlotinib	15	0

Primary outcome: Number of Participants With Progression-free Survival

Time frame: through study completion, an average of 3 years

Population analysed: Early termination due to a change in drug FDA approval. No subject completed study. No data analysis was completed. No data collected.

1 secondary outcome is reported in the full results.

Adverse events

Time frame: 5 years. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Fulvestrant Plus Placebo	2 of 12 (16.7%)	3 of 12 (25%)	8 of 12
Fulvestrant Plus Erlotinib	3 of 15 (20%)	5 of 15 (33.3%)	3 of 15

Limitations and caveats (from the sponsor): Early termination due to a change in drug FDA approval. Outcome measures not computed because data would not be statistically relevant.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 30 Mar 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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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.

Issam Makhoul, MD principal investigator

University of Arkansas

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

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Fulvestrant and erlotinib in people with Metastatic Breast Cancer, run by University of Arkansas at 6 sites 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 6 inclusion and 12 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: stopped early, as of the sponsor's last update on 30 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

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 6 Feb 2019). 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?

Number of Participants With Progression-free Survival (time frame: through study completion, an average of 3 years). 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 NCT00570258.

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 30 Mar 2021.