Breast CancerPhase 1NCT00068757
Lonafarnib, Trastuzumab, and Paclitaxel in Treating Patients With HER2/Neu-Overexpressing Stage IIIB, Stage IIIC, or Stage IV Breast Cancer
A Phase 1 study testing trastuzumab, lonafarnib and paclitaxel in people with Breast Cancer, run by European Organisation for Research and Treatment of Cancer - EORTC at 3 sites in 3 countries.
Trial summary
RATIONALE: Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop tumor cells from dividing so they stop growing or die. Lonafarnib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer
- What is being tested?
- trastuzumab, lonafarnib and paclitaxel
- How many people
- 23 participants
- Where
- 3 sitesin 3 countries
- Study dates
- Aug 2003to Nov 2007
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- All sexes
- No healthy volunteers
- Adult, Older adult
DISEASE CHARACTERISTICS:
- Histologically or cytologically confirmed breast cancer
- Stage IIIB, IIIC, or IV
- HER2/neu overexpression
- 3+ by immunohistochemistry
- 2+ allowed if positive fluorescent in situ hybridization
- Disease meets the following treatment criteria:
- Paclitaxel/trastuzumab (Herceptin®) may be appropriate therapy
- Anthracycline therapy is not a suitable approach
- No clinical signs of CNS involvement
- Hormone receptor status:
- Not specified
PATIENT CHARACTERISTICS:
Age
- 18 and over
Sex
- Male or female
Menopausal status
- Not specified
Performance status
- ECOG 0-2 OR
- WHO 0-2
Life expectancy
- Not specified
Hematopoietic
- Neutrophil count at least 1,500/mm^3
- Platelet count at least 100,000/mm^3
- Hemoglobin at least 10.0 g/dL (6.2 mmol/L)
Hepatic
- Bilirubin no greater than 1.5 times upper limit of normal (ULN)
- Alkaline phosphatase less than 2.5 times ULN (5 times ULN if liver metastases are present)
- AST and ALT less than 2.5 times ULN (5 times ULN if liver metastases are present)
Renal
- Creatinine clearance at least 40 mL/min
Cardiovascular
- Cardiac ejection fraction normal by MUGA
- QTc interval no greater than 440 msec
- No cardiac dysfunction
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for up to 3 months after study participation
- No concurrent severe/unstable systemic disease
- No infection
- No circumstances that would preclude study participation (e.g., alcoholism or substance abuse)
- No psychological, familial, sociological, or geographical condition that would preclude study compliance and follow-up
PRIOR CONCURRENT THERAPY:
Biologic therapy
- More than 1 year since prior trastuzumab
- No concurrent prophylactic growth factors
Chemotherapy
- More than 1 year since prior paclitaxel
- More than 4 weeks since other prior chemotherapy
Endocrine therapy
- More than 1 day since prior hormonal therapy
- More than 2 days since prior high-dose chronic steroids
- More than 2 days since prior ethinyl estradiol
- No concurrent high-dose chronic steroids
- No concurrent ethinyl estradiol
Radiotherapy
- More than 4 weeks since prior radiotherapy
Surgery
- Not specified
Other
- More than 2 days since prior administration of and no concurrent CYP3A4 inducers or inhibitors, including any of the following:
- Gestodene
- Itraconazole
- Ketoconazole
- Cimetidine
- Erythromycin
- Carbamazepine
- Phenobarbital
- Phenytoin
- Rifampin
- Sulfinpyrazone
- No concurrent grapefruit juice
- No other concurrent anticancer agents
- No other concurrent investigational therapy
Trial locations and contacts
3 sites in 3 countries.
3 sites in 3 countries
Netherlands1 site
Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital
Amsterdam, 1066 CX
About this study
Official title: Phase I Study of Lonafarnib (SCH66336) in Combination With Herceptin Plus Paclitaxel in HER 2 NEU Overexpressing Breast Cancer
RATIONALE: Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop tumor cells from dividing so they stop growing or die. Lonafarnib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Monoclonal antibodies, such as trastuzumab, can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Combining lonafarnib and trastuzumab with paclitaxel may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of lonafarnib when given together with trastuzumab and paclitaxel in treating patients with HER2/neu-overexpressing stage IIIB, stage IIIC, or stage IV breast cancer.
Read the detailed description
OBJECTIVES:
Primary
- Determine the maximum tolerated dose and recommended phase II dose of lonafarnib in combination with trastuzumab (Herceptin®) and paclitaxel in patients with HER2/neu-overexpressing stage IIIB, IIIC, or IV breast cancer.
- Determine the qualitative and quantitative toxicity of this regimen in these patients.
Secondary
- Determine the pharmacokinetic profiles of these drugs in these patients.
- Correlate the pharmacodynamics with the pharmacokinetics of this regimen in these patients.
- Correlate the pharmacokinetics and pharmacodynamics of this regimen with observed toxicity in these patients.
- Determine the response to this regimen in patients with measurable disease.
OUTLINE: This is a nonrandomized, open-label, multicenter, dose-escalation study of lonafarnib.
- Course 1: Patients receive a loading dose of trastuzumab (Herceptin®) IV over 90 minutes on day 1 and over 30 minutes on days 8 and 15. Patients also receive paclitaxel IV over 3 hours on day 1.
- Course 2: Patients receive trastuzumab IV over 30 minutes on days 1, 8, and 15 and paclitaxel IV over 3 hours on day 2. Patients also receive oral lonafarnib twice daily on days 3-21.
- Course 3 and all subsequent courses: Patients receive oral lonafarnib twice daily on days 1-21; trastuzumab IV over 30 minutes on days 1, 8, and 15; and paclitaxel IV over 3 hours on day 1.
Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of lonafarnib 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.
Patients are followed every 8 weeks until disease progression.
PROJECTED ACCRUAL: A total of 3-36 patients will be accrued for this study.
- Conditions
- Breast Cancer
- Being tested
- trastuzumab, lonafarnib, paclitaxel, pharmacological study
- Keywords
- recurrent breast cancer, stage IIIB breast cancer, stage IIIC breast cancer, stage IV breast cancer, male breast cancer, HER2-positive breast cancer
- Medical subject headings
- Breast Neoplasms, Breast Neoplasms, Male
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
trastuzumabBiological
lonafarnibDrug
paclitaxelDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose-limiting toxicity and maximum tolerated dose as measured by CTC v 2.0
Secondary outcomes (3)
Translational research
Pharmacokinetics (PK) and pharmacodynamics (PD)
Clinical response as measured by RECIST criteria
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Sep 2003 (estimated)
- Study startAug 2003
- Primary completionNov 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by European Organisation for Research and Treatment of Cancer - EORTCThe 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
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Sponsor type
- Research network
- Responsible party
- Sponsor
- Investigators
- Jan H. M. Schellens, MD, PhD, Study chair, The Netherlands Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00068757
- Sponsor's protocol ID
- EORTC-16023-10051
- Other IDs
- EORTC-16023-10051, SPRI-P01900
- Status last verified
- Sep 2012
- First submitted
- 10 Sep 2003
- Last updated
- 12 Sep 2012
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Sep 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of Lonafarnib (SCH66336) in Combination With Herceptin Plus Paclitaxel in HER 2 NEU Overexpressing Breast Cancer
- ClinicalTrials.gov ID
- NCT00068757
- Acronym / sponsor ID
- EORTC-16023-10051
- Conditions
- Breast Cancer
- Keywords
- recurrent breast cancer, stage IIIB breast cancer, stage IIIC breast cancer, stage IV breast cancer, male breast cancer, HER2-positive breast cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- European Organisation for Research and Treatment of Cancer - EORTCResearch network
- Study start
- Aug 2003
- Primary completion
- Nov 2007 (actual)
- First posted
- 11 Sep 2003 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop tumor cells from dividing so they stop growing or die. Lonafarnib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Monoclonal antibodies, such as trastuzumab, can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Combining lonafarnib and trastuzumab with paclitaxel may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of lonafarnib when given together with trastuzumab and paclitaxel in treating patients with HER2/neu-overexpressing stage IIIB, stage IIIC, or stage IV breast cancer.
Detailed description
OBJECTIVES:
Primary
- Determine the maximum tolerated dose and recommended phase II dose of lonafarnib in combination with trastuzumab (Herceptin®) and paclitaxel in patients with HER2/neu-overexpressing stage IIIB, IIIC, or IV breast cancer.
- Determine the qualitative and quantitative toxicity of this regimen in these patients.
Secondary
- Determine the pharmacokinetic profiles of these drugs in these patients.
- Correlate the pharmacodynamics with the pharmacokinetics of this regimen in these patients.
- Correlate the pharmacokinetics and pharmacodynamics of this regimen with observed toxicity in these patients.
- Determine the response to this regimen in patients with measurable disease.
OUTLINE: This is a nonrandomized, open-label, multicenter, dose-escalation study of lonafarnib.
- Course 1: Patients receive a loading dose of trastuzumab (Herceptin®) IV over 90 minutes on day 1 and over 30 minutes on days 8 and 15. Patients also receive paclitaxel IV over 3 hours on day 1.
- Course 2: Patients receive trastuzumab IV over 30 minutes on days 1, 8, and 15 and paclitaxel IV over 3 hours on day 2. Patients also receive oral lonafarnib twice daily on days 3-21.
- Course 3 and all subsequent courses: Patients receive oral lonafarnib twice daily on days 1-21; trastuzumab IV over 30 minutes on days 1, 8, and 15; and paclitaxel IV over 3 hours on day 1.
Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of lonafarnib 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.
Patients are followed every 8 weeks until disease progression.
PROJECTED ACCRUAL: A total of 3-36 patients will be accrued for this study.
Study design
- Primary purpose
- Treatment
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| trastuzumab | Biological | – |
| lonafarnib | Drug | – |
| paclitaxel | Drug | – |
| pharmacological study | Other | – |
Primary outcome
Dose-limiting toxicity and maximum tolerated dose as measured by CTC v 2.0
3 secondary outcomes
Translational research
Pharmacokinetics (PK) and pharmacodynamics (PD)
Clinical response as measured by RECIST criteria
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Sep 2012.
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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.
Jan H. M. Schellens, MD, PhD study chair
The Netherlands Cancer Institute
3 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing trastuzumab, lonafarnib and paclitaxel in people with Breast Cancer, run by European Organisation for Research and Treatment of Cancer - EORTC at 3 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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 12 Sep 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Belgium, France, Netherlands. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Dose-limiting toxicity and maximum tolerated dose as measured by CTC v 2.0. 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 12 Sep 2012.