Metastatic Breast CancerPhase 1NCT00426556
Efficacy and Safety of Everolimus in Combination Therapy, in Patients With HER2-overexpressing Metastatic Breast Cancer
A Phase 1 study testing Everolimus, Trastuzumab and Paclitaxel in people with Metastatic Breast Cancer, run by Novartis Pharmaceuticals at 20 sites in 5 countries.
Trial summary
Phase I: will look at different dose levels and regimens of everolimus combined with weekly trastuzumab and paclitaxel therapy in patients with HER-2 overexpressing metastatic breast cancer. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Metastatic Breast Cancer
- What is being tested?
- Everolimus, Trastuzumab and Paclitaxel
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 88 participants
- Where
- 20 sitesin 5 countries
- Study dates
- Jul 2007to Mar 2014
- Phase
- Phase 1
- 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
- Female or male patients ≥ 18 years old with WHO performance status ≤ 1
- HER-2 over-expressing metastatic breast cancer cells confirmed by histology
- Progressive disease on prior trastuzumab alone/or in combination with other anticancer agents, or relapsed any time after completion of this therapy (phase l)
- Patient resistance to trastuzumab and taxanes (Phase ll)
- Measurable disease according to RECIST (Phase ll)
- Patients neurologically stable with adequate bone marrow, liver and renal function
Who cannot join
- Patients receiving endocrine therapy for breast cancer ≤ 2 weeks prior to study treatment start
- Patients currently receiving chemotherapy, immunotherapy or radiotherapy or who have received these ≤ 4 weeks prior to study treatment start or patients who have received lapatinib ≤ 2 weeks prior to study treatment start
- Patients who have previously received mTOR inhibitors
- Other protocol-defined inclusion/exclusion criteria may apply
Trial locations and contacts
20 sites in 5 countries.
20 sites in 5 countries
United States11 sites
Wilshire Oncology Medical Group La Verne
*see Various Departments*, California
Emory University School of Medicine/Winship Cancer Institute Dept. of Hematology (2)
Atlanta, Georgia, 30322
Sammons Cancer Center - Texas Oncology
Dallas, Texas, 78246
Florida Cancer Research Institute
Davie, Florida, 33328
North Shore University Health System
Evanston, Illinois, 60201
Compassionate Cancer Care Medical Group Dept.ofCCCMG
Fountain Valley, California, 92708
Cancer Centers of the Carolinas CC of C -Eastside
Greenville, South Carolina, 29605
Loma Linda University Dept.ofLomaLindaCancerCent(3)
Loma Linda, California, 92354
University of California at Los Angeles Dept.of UCLA Dept.ofMed.
Los Angeles, California, 90095
Peninsula Regional Medical Center Deptof Oncology and Hematology
Salisbury, Maryland, 21801
Washington University School Of Medicine-Siteman Cancer Ctr StudyCoordinator:CRAD001J2101
St Louis, Missouri, 63110
France4 sites
Novartis Investigative Site
Paris, 75970
Novartis Investigative Site
Saint-Herblain Cédex, 44805
Novartis Investigative Site
Toulouse, 31059
Novartis Investigative Site
Villejuif, 94805
Belgium3 sites
Novartis Investigative Site
Charleroi, 6000
Novartis Investigative Site
Liège, 4000
Novartis Investigative Site
Turnhout, 2300
About this study
Official title: A Phase Ib/II Study Investigating the Combination of Everolimus With Trastuzumab and Paclitaxel in Patients With HER2-overexpressing Metastatic Breast Cancer
Phase I: will look at different dose levels and regimens of everolimus combined with weekly trastuzumab and paclitaxel therapy in patients with HER-2 overexpressing metastatic breast cancer.
Phase II: will assess the efficacy and safety of the 10mg daily dose of everolimus combined with weekly trastuzumab and paclitaxel therapy in patients with HER-2 overexpressing metastatic breast cancer.
- Conditions
- Metastatic Breast Cancer
- Being tested
- Everolimus, Trastuzumab, Paclitaxel
- Keywords
- Breast cancer, Cancer of the breast, Human mammary carcinoma, HER-2, Metastatic, everolimus, trastuzumab, paclitaxel
- Medical subject headings
- Breast Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EverolimusDrug
Also called RAD001
Everolimus (RAD001) was supplied as tablets in 3 different dosage strengths, 2.5, 5, and 10 mg. The drug was packaged in blisters containing 10 tablets per blister. Blisters and packaging labels were compliant with local regulations and were printed in local language.
TrastuzumabDrug
Commercially-available trastuzumab was used in this study. A 4 mg/kg loading dose was administered, intra-venous (IV), over 90 minutes on Day 1 (if patient was not already receiving trastuzumab); this was followed by weekly trastuzumab 2 mg/kg IV administered over 30 minutes. For patients who continued to receive trastuzumab and everolimus after completion/discontinuation of chemotherapy in the core treatment phase, trastuzumab may have been administered once every 3 weeks at a dose of 6 mg/kg. PT = Paclitaxel \& Trastuzumab
PaclitaxelDrug
Commercially-available paclitaxel was used in this study. Paclitaxel infusion was administered on Days 1, 8, and 15 of each 28-day cycle, after administration of trastuzumab. Paclitaxel (80 mg/m2) was administered as a 60-minute continuous IV infusion after standard premedication. Patients received paclitaxel for 6 cycles. At the investigator's discretion, treatment with paclitaxel could continue beyond 6 cycles.
| Study group | Role | What they receive |
|---|---|---|
| Phase I - RAD001 5mg + PT, daily | Experimental | Daily dosing schedule of EPT = Paclitaxel \& Trastuzumab verolimus 5mg plus Paclitaxel plus Trastuzumab. Receives: Drug: Everolimus; Drug: Trastuzumab; Drug: Paclitaxel |
| Phase I - RAD001 10mg + PT, daily | Experimental | Daily dosing schedule of Everolimus 10mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel \& Trastuzumab Receives: Drug: Everolimus; Drug: Trastuzumab; Drug: Paclitaxel |
| Phase I - RAD001 30mg + PT, weekly | Experimental | Weekly dosing schedule of Everolimus 30mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel \& Trastuzumab. Receives: Drug: Everolimus; Drug: Trastuzumab; Drug: Paclitaxel |
| Phase II - RAD001 10mg + PT, daily | Experimental | Daily dosing schedule of Everolimus 10mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel \& Trastuzumab Receives: Drug: Everolimus; Drug: Trastuzumab; Drug: Paclitaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase II: Overall Response Rate
The primary objective of this phase II study was to evaluate the efficacy of the dose level/regimen of everolimus recommended from the Phase I with trastuzumab and paclitaxel (PT) therapy in patients with HER2-overexpressing metastatic breast cancer whose disease progressed on/after trastuzumab mono-and/or combination therapy based on the evaluation of objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Objective response rate (ORR) was defined as the proportion of patients with a best overall response (BOR) of complete response (CR) or partial response (PR). Only patients with measurable disease (the presence of at least one measurable lesion) at baseline were included in the study. CR = Disappearance of all target lesions; PR = At least a 30% decrease in the sum of the longest diameter of all target lesions, taking as reference the baseline sum of the longest diameters.
Measured: every 8 - 9 weeks until disease progression or a new lesion is identified
Secondary outcomes (3)
Phase I: Best Overall Response (BOR)
BOR was determined based on investigator assessment of overall lesion response using RECIST criteria guidelines. BOR = objective responses rate (ORR), disease control rate (DCR) or clinical benefit rate (CBR). ORR = (complete response (CR) or partial response(PR); DCR = (CR or PR or Stable disease (SD); CBR = (CR or PR or SD >= 24 weeks).CR = Disappearance of all target lesions; PR = At least a 30% decrease in the sum of the longest diameter of all target lesions, taking as reference the baseline sum of the longest diameters; SD = Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for partial disease (PD). PD = At least a 20% increase in the sum of the longest diameter of all measured target lesions, taking as reference the smallest sum of longest diameter of all target lesions recorded at or after baseline.
Measured: every 8 - 9 weeks until disease progression or a new lesion is identified
Phase II: Progression Free Survival (PFS)
PFS is defined as the time from start of treatment to the date of first documented progression or death due to any cause. If a patient has not had an event, PFS will be censored at the date of last adequate tumor assessment.
Measured: every 8 - 9 weeks until disease progression or a new lesion is identified
Phase II: Overall Survival (OS)
Overall survival (OS) is defined as the time from start of treatment to the date of death due to any cause. If a patient is not known to have died, survival was censored at the last date of contact. OS was to be reported at extension and after 3-year follow-up. The Kaplan-Meier median was used to analyze the OS.
Measured: every 3 months until death
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jan 2007 (estimated)
- Study startJul 2007
- Primary completionMar 2014
- Study completionMar 2014
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.
- More trials run by Novartis PharmaceuticalsThe 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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 88 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00426556
- Sponsor's protocol ID
- CRAD001J2101
- Other IDs
- 2006-001596-37
- Status last verified
- Nov 2015
- First submitted
- 23 Jan 2007
- Last updated
- 28 Dec 2015
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 28 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib/II Study Investigating the Combination of Everolimus With Trastuzumab and Paclitaxel in Patients With HER2-overexpressing Metastatic Breast Cancer
- ClinicalTrials.gov ID
- NCT00426556
- Acronym / sponsor ID
- CRAD001J2101
- Conditions
- Metastatic Breast Cancer
- Keywords
- Breast cancer, Cancer of the breast, Human mammary carcinoma, HER-2, Metastatic, everolimus, trastuzumab, paclitaxel
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 88 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Jul 2007
- Primary completion
- Mar 2014 (actual)
- Study completion
- Mar 2014 (actual)
- First posted
- 24 Jan 2007 (estimated)
- Results
- Posted 31 Mar 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Phase I: will look at different dose levels and regimens of everolimus combined with weekly trastuzumab and paclitaxel therapy in patients with HER-2 overexpressing metastatic breast cancer.
Phase II: will assess the efficacy and safety of the 10mg daily dose of everolimus combined with weekly trastuzumab and paclitaxel therapy in patients with HER-2 overexpressing metastatic breast cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Phase I - RAD001 5mg + PT, daily | Experimental | Drug: Everolimus, Drug: Trastuzumab, Drug: PaclitaxelDaily dosing schedule of EPT = Paclitaxel \& Trastuzumab verolimus 5mg plus Paclitaxel plus Trastuzumab. |
| Phase I - RAD001 10mg + PT, daily | Experimental | Drug: Everolimus, Drug: Trastuzumab, Drug: PaclitaxelDaily dosing schedule of Everolimus 10mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel \& Trastuzumab |
| Phase I - RAD001 30mg + PT, weekly | Experimental | Drug: Everolimus, Drug: Trastuzumab, Drug: PaclitaxelWeekly dosing schedule of Everolimus 30mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel \& Trastuzumab. |
| Phase II - RAD001 10mg + PT, daily | Experimental | Drug: Everolimus, Drug: Trastuzumab, Drug: PaclitaxelDaily dosing schedule of Everolimus 10mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel \& Trastuzumab |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Female or male patients ≥ 18 years old with WHO performance status ≤ 1
- HER-2 over-expressing metastatic breast cancer cells confirmed by histology
- Progressive disease on prior trastuzumab alone/or in combination with other anticancer agents, or relapsed any time after completion of this therapy (phase l)
- Patient resistance to trastuzumab and taxanes (Phase ll)
- Measurable disease according to RECIST (Phase ll)
Key exclusion criteria (4 listed)
- Patients receiving endocrine therapy for breast cancer ≤ 2 weeks prior to study treatment start
- Patients currently receiving chemotherapy, immunotherapy or radiotherapy or who have received these ≤ 4 weeks prior to study treatment start or patients who have received lapatinib ≤ 2 weeks prior to study treatment start
- Patients who have previously received mTOR inhibitors
- Other protocol-defined inclusion/exclusion criteria may apply
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 |
|---|---|---|
| EverolimusAlso: RAD001Everolimus (RAD001) was supplied as tablets in 3 different dosage strengths, 2.5, 5, and 10 mg. The drug was packaged in blisters containing 10 tablets per blister. Blisters and packaging labels were compliant with local regulations and were printed in local language. | Drug | Phase I - RAD001 10mg + PT, daily, Phase I - RAD001 30mg + PT, weekly, Phase I - RAD001 5mg + PT, daily, Phase II - RAD001 10mg + PT, daily |
| TrastuzumabCommercially-available trastuzumab was used in this study. A 4 mg/kg loading dose was administered, intra-venous (IV), over 90 minutes on Day 1 (if patient was not already receiving trastuzumab); this was followed by weekly trastuzumab 2 mg/kg IV administered over 30 minutes. For patients who continued to receive trastuzumab and everolimus after completion/discontinuation of chemotherapy in the core treatment phase, trastuzumab may have been administered once every 3 weeks at a dose of 6 mg/kg. PT = Paclitaxel \& Trastuzumab | Drug | Phase I - RAD001 10mg + PT, daily, Phase I - RAD001 30mg + PT, weekly, Phase I - RAD001 5mg + PT, daily, Phase II - RAD001 10mg + PT, daily |
| PaclitaxelCommercially-available paclitaxel was used in this study. Paclitaxel infusion was administered on Days 1, 8, and 15 of each 28-day cycle, after administration of trastuzumab. Paclitaxel (80 mg/m2) was administered as a 60-minute continuous IV infusion after standard premedication. Patients received paclitaxel for 6 cycles. At the investigator's discretion, treatment with paclitaxel could continue beyond 6 cycles. | Drug | Phase I - RAD001 10mg + PT, daily, Phase I - RAD001 30mg + PT, weekly, Phase I - RAD001 5mg + PT, daily, Phase II - RAD001 10mg + PT, daily |
Primary outcome
Phase II: Overall Response Rate
Time frame: every 8 - 9 weeks until disease progression or a new lesion is identified
The primary objective of this phase II study was to evaluate the efficacy of the dose level/regimen of everolimus recommended from the Phase I with trastuzumab and paclitaxel (PT) therapy in patients with HER2-overexpressing metastatic breast cancer whose disease progressed on/after trastuzumab mono-and/or combination therapy based on the evaluation of objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Objective response rate (ORR) was defined as the proportion of patients with a best overall response (BOR) of complete response (CR) or partial response (PR). Only patients with measurable disease (the presence of at least one measurable lesion) at baseline were included in the study. CR = Disappearance of all target lesions; PR = At least a 30% decrease in the sum of the longest diameter of all target lesions, taking as reference the baseline sum of the longest diameters.
3 secondary outcomes
Phase I: Best Overall Response (BOR)
Time frame: every 8 - 9 weeks until disease progression or a new lesion is identified
Phase II: Progression Free Survival (PFS)
Time frame: every 8 - 9 weeks until disease progression or a new lesion is identified
Phase II: Overall Survival (OS)
Time frame: every 3 months until death
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Dec 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Visit NovartisClinicalTrials.com: Pre-qualify for a trial, and view a list of trials and participating study centers.Link provided by the sponsor.
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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.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
20 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Everolimus, Trastuzumab and Paclitaxel in people with Metastatic Breast Cancer, run by Novartis Pharmaceuticals at 20 sites in 5 countries.
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 4 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 28 Dec 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites in United States, France, Belgium, Netherlands, Spain. 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 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.
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 31 Mar 2015). 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?
Phase II: Overall Response Rate (time frame: every 8 - 9 weeks until disease progression or a new lesion is identified). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 28 Dec 2015.