Inflammatory Breast CancerPhase 2NCT00049114
Tipifarnib, Doxorubicin, and Cyclophosphamide in Treating Women With Locally Advanced Breast Cancer
A Phase 2 study testing doxorubicin hydrochloride, cyclophosphamide and tipifarnib in people with Inflammatory Breast Cancer and Stage II Breast Cancer, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
Drugs used in chemotherapy, such as doxorubicin and cyclophosphamide, work in different ways to stop tumor cells from dividing so they stop growing or die. Tipifarnib 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, women only
- Conditions the study is for
- Inflammatory Breast Cancer, Stage II Breast Cancer, Stage IIIA Breast Cancer
- What is being tested?
- doxorubicin hydrochloride, cyclophosphamide and tipifarnib
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 62 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2003to Jan 2007
- Phase
- Phase 2
- 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
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically or cytologically confirmed adenocarcinoma of the breast
- Phase I (closed to accrual as of 1/19/04):
- Nonregional stage IV disease
- Phase II:
- Locally advanced disease, according to AJCC staging criteria:
- Stage IIB
Show all 55Show fewer
- Stage IIIA
- Stage IIIB
- Stage IIIC
- At least 1 bidimensionally or unidimensionally measurable indicator lesion
- Hormone receptor status:
- Not specified
- Female
- Performance status - ECOG 0-1
- Performance status - Karnofsky 70-100%
- Not specified
- WBC at least 3,000/mm^3
- Absolute neutrophil count at least 1,500/mm^3
- Platelet count at least 100,000/mm^3
- Bilirubin normal
- AST/ALT no greater than 2.5 times upper limit of normal
- Creatinine normal
- Creatinine clearance at least 60 mL/min
- LVEF normal
- No symptomatic congestive heart failure
- No unstable angina pectoris
- No cardiac arrhythmia
- No other invasive malignancies within the past 5 years except curatively treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
- No prior allergic reactions attributed to compounds of similar chemical or biological composition to tipifarnib or other agents used in the study (e.g., imidazoles or quinolones)
- No ongoing or active infection
- No other concurrent uncontrolled illness that would preclude study participation
- No psychiatric illness or social situation that would preclude study compliance
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- Not specified
- Phase I (closed to accrual as of 1/19/04):
- More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
- No more than 1 prior adjuvant/neoadjuvant regimen and 1 prior regimen for metastatic disease
- Prior doxorubicin allowed provided the following are true:
- Used in adjuvant setting
- Cumulative dose was no greater than 240 mg/m^2
- At least 1 year between completion of adjuvant therapy and relapse
- Phase II:
- No prior chemotherapy for locally advanced breast cancer
- At least 1 week since prior tamoxifen or other selective estrogen receptor modulators for prevention or other indications (e.g., osteoporosis, ductal carcinoma in situ, or invasive breast cancer)
- Phase I (closed to accrual as of 1/19/04):
- More than 4 weeks since prior radiotherapy
- Phase II:
- No prior radiotherapy for locally advanced breast cancer
- Not specified
- No antacids within 2 hours of study drug administration
- No concurrent combination antiretroviral therapy for HIV-positive patients
- No other concurrent anticancer therapy
- No other concurrent investigational agents
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
United States1 site
Albert Einstein College of Medicine
The Bronx, New York, 10461
About this study
Official title: A Phase I-II Study of R115777 (ZARNESTRA) Plus Doxorubicin and Cyclophosphamide in Patients With Locally Advanced Breast Cancer and Metastatic Breast Cancer
Drugs used in chemotherapy, such as doxorubicin and cyclophosphamide, work in different ways to stop tumor cells from dividing so they stop growing or die. Tipifarnib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Combining tipifarnib with doxorubicin and cyclophosphamide may kill more tumor cells. Phase II trial to study the effectiveness of combining tipifarnib with doxorubicin and cyclophosphamide in treating women who have locally advanced breast cancer.
Read the detailed description
PRIMARY OBJECTIVES:
- Determine the maximum tolerated dose of tipifarnib when administered with doxorubicin and cyclophosphamide in women with metastatic breast cancer (non-regional stage IV disease). (Phase I closed to accrual as of 1/19/04) II. Determine the pathologic complete remission rate in patients with locally advanced breast cancer (stages IIB, IIIA, IIIB, or IIIC) treated with the recommended phase II dose of this regimen.
SECONDARY OBJECTIVES:
- Determine the clinical complete response rate in patients treated with this regimen.
II. Determine the toxicity profile of this regimen in these patients. III. Correlate pretreatment levels of ErbB1, 2, 3, 4 and phosphorylated levels of Akt, STAT3, and Erk ½ with clinical response in these patients and with percent inhibition of proliferation (Ki-67) and percent induction of apoptosis in post-treatment tumor specimens.
IV. Correlate percent decrease of farnesyltransferase (FTase) activity levels, HDJ-2 farnesylation, phospho-Akt, phospho-STAT3, and phospho-Erk ½ with clinical response rates in these patients and with percent inhibition of proliferation (Ki-67) and percent inhibition of apoptosis.
OUTLINE: This is a multicenter, dose-escalation study of tipifarnib. Patients are stratified according to presence of inflammatory carcinoma (yes vs no).
PHASE I (nonregional stage IV disease) (closed to accrual as of 1/19/04): Patients receive doxorubicin IV over 10-15 minutes and cyclophosphamide IV over 30 minutes on day 1, oral tipifarnib twice daily on days 2-7, and filgrastim (G-CSF) subcutaneously on days 2-13. Treatment repeats every 2 weeks for 4 courses in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of tipifarnib 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.
PHASE II (stage IIB, IIIA, IIIB, or IIIC): Patients receive tipifarnib at the MTD and doxorubicin, cyclophosphamide, and G-CSF as in phase I (phase I closed to accrual as of 1/19/04). After the fourth course, patients may undergo complete resection.
Patients are followed every 3-4 months for 3 years, every 6 months for 2 years, and then annually thereafter.
PROJECTED ACCRUAL: Approximately 3-12 patients will be accrued for phase I (closed to accrual as of 1/19/04) of this study. A total of 21-50 patients will be accrued for phase II of this study.
- Conditions
- Inflammatory Breast Cancer, Stage II Breast Cancer, Stage IIIA Breast Cancer, Stage IIIB Breast Cancer, Stage IIIC Breast Cancer
- Being tested
- doxorubicin hydrochloride, cyclophosphamide, tipifarnib, filgrastim, therapeutic conventional surgery
- Medical subject headings
- Inflammatory Breast Neoplasms, Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Also called ADM, ADR, Adria, Adriamycin PFS
cyclophosphamideDrug
Also called CPM, CTX, Cytoxan, Endoxan
Given IV
tipifarnibDrug
Also called R115777, Zarnestra
Given orally
filgrastimBiological
Also called G-CSF, Neupogen
Given subcutaneously
therapeutic conventional surgeryProcedure or surgery
Undergo complete resection
laboratory biomarker analysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (doxorubicin, cyclophosphamide, tipifarnib, G-CSF) | Experimental | PHASE I (nonregional stage IV disease) (closed to accrual as of 1/19/04): Patients receive doxorubicin IV over 10-15 minutes and cyclophosphamide IV over 30 minutes on day 1, oral tipifarnib twice daily on days 2-7, and G-CSF subcutaneously on days 2-13. Treatment repeats every 2 weeks for 4 courses in the absence of disease progression or unacceptable toxicity.
PHASE II (stage IIB, IIIA, IIIB, or IIIC): Patients receive tipifarnib at the MTD and doxorubicin, cyclophosphamide, and G-CSF as in phase I (phase I closed to accrual as of 1/19/04). After the fourth course, patients may undergo complete resection. Receives: Drug: doxorubicin hydrochloride; Drug: cyclophosphamide; Drug: tipifarnib; Biological: filgrastim; Procedure: therapeutic conventional surgery; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pathological complete response in the breast
95% confidence intervals of these estimates will be obtained.
Measured: 8 weeks
Secondary outcomes (5)
Proportion of patients who have a clinical complete response
95% confidence intervals of these estimates will be obtained.
Measured: 8 weeks
Grade 3 or 4 toxicities assessed using NCI CTCAE version 3.0
Toxicity will be summarized by type, frequency and severity. This will be compared with an historical database.
Measured: Up to 5 years
Median disease-free survival
Will be summarized, and 95% confidence intervals of these estimates will be obtained.
Measured: Up to 5 years
Percentage of patients free of disease
Will be summarized, and 95% confidence intervals of these estimates will be obtained.
Measured: 1 year
Percentage of patients free of disease
Will be summarized, and 95% confidence intervals of these estimates will be obtained.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2003 (estimated)
- Study startFeb 2003
- Primary completionJan 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Inflammatory Breast CancerStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 62 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Joseph Sparano, Principal investigator, Albert Einstein College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00049114
- Sponsor's protocol ID
- NCI-2012-02500
- Other IDs
- 02-05-125, AECM-0205125, NCI-5598, CDR0000257811, N01CM62204
- Status last verified
- Jun 2013
- First submitted
- 12 Nov 2002
- Last updated
- 6 Jun 2013
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Jun 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I-II Study of R115777 (ZARNESTRA) Plus Doxorubicin and Cyclophosphamide in Patients With Locally Advanced Breast Cancer and Metastatic Breast Cancer
- ClinicalTrials.gov ID
- NCT00049114
- Acronym / sponsor ID
- NCI-2012-02500
- Conditions
- Inflammatory Breast Cancer, Stage II Breast Cancer, Stage IIIA Breast Cancer, Stage IIIB Breast Cancer, Stage IIIC Breast Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 62 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Feb 2003
- Primary completion
- Jan 2007 (actual)
- First posted
- 27 Jan 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.
Drugs used in chemotherapy, such as doxorubicin and cyclophosphamide, work in different ways to stop tumor cells from dividing so they stop growing or die. Tipifarnib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Combining tipifarnib with doxorubicin and cyclophosphamide may kill more tumor cells. Phase II trial to study the effectiveness of combining tipifarnib with doxorubicin and cyclophosphamide in treating women who have locally advanced breast cancer.
Detailed description
PRIMARY OBJECTIVES:
- Determine the maximum tolerated dose of tipifarnib when administered with doxorubicin and cyclophosphamide in women with metastatic breast cancer (non-regional stage IV disease). (Phase I closed to accrual as of 1/19/04) II. Determine the pathologic complete remission rate in patients with locally advanced breast cancer (stages IIB, IIIA, IIIB, or IIIC) treated with the recommended phase II dose of this regimen.
SECONDARY OBJECTIVES:
- Determine the clinical complete response rate in patients treated with this regimen.
II. Determine the toxicity profile of this regimen in these patients. III. Correlate pretreatment levels of ErbB1, 2, 3, 4 and phosphorylated levels of Akt, STAT3, and Erk ½ with clinical response in these patients and with percent inhibition of proliferation (Ki-67) and percent induction of apoptosis in post-treatment tumor specimens.
IV. Correlate percent decrease of farnesyltransferase (FTase) activity levels, HDJ-2 farnesylation, phospho-Akt, phospho-STAT3, and phospho-Erk ½ with clinical response rates in these patients and with percent inhibition of proliferation (Ki-67) and percent inhibition of apoptosis.
OUTLINE: This is a multicenter, dose-escalation study of tipifarnib. Patients are stratified according to presence of inflammatory carcinoma (yes vs no).
PHASE I (nonregional stage IV disease) (closed to accrual as of 1/19/04): Patients receive doxorubicin IV over 10-15 minutes and cyclophosphamide IV over 30 minutes on day 1, oral tipifarnib twice daily on days 2-7, and filgrastim (G-CSF) subcutaneously on days 2-13. Treatment repeats every 2 weeks for 4 courses in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of tipifarnib 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.
PHASE II (stage IIB, IIIA, IIIB, or IIIC): Patients receive tipifarnib at the MTD and doxorubicin, cyclophosphamide, and G-CSF as in phase I (phase I closed to accrual as of 1/19/04). After the fourth course, patients may undergo complete resection.
Patients are followed every 3-4 months for 3 years, every 6 months for 2 years, and then annually thereafter.
PROJECTED ACCRUAL: Approximately 3-12 patients will be accrued for phase I (closed to accrual as of 1/19/04) of this study. A total of 21-50 patients will be accrued for phase II 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 (doxorubicin, cyclophosphamide, tipifarnib, G-CSF) | Experimental | Drug: doxorubicin hydrochloride, Drug: cyclophosphamide, Drug: tipifarnib, Biological: filgrastim, Procedure: therapeutic conventional surgery, Other: laboratory biomarker analysisPHASE I (nonregional stage IV disease) (closed to accrual as of 1/19/04): Patients receive doxorubicin IV over 10-15 minutes and cyclophosphamide IV over 30 minutes on day 1, oral tipifarnib twice daily on days 2-7, and G-CSF subcutaneously on days 2-13. Treatment repeats every 2 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. PHASE II (stage IIB, IIIA, IIIB, or IIIC): Patients receive tipifarnib at the MTD and doxorubicin, cyclophosphamide, and G-CSF as in phase I (phase I closed to accrual as of 1/19/04). After the fourth course, patients may undergo complete resection. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (55 listed)
- Histologically or cytologically confirmed adenocarcinoma of the breast
- Phase I (closed to accrual as of 1/19/04):
- Phase II:
- At least 1 bidimensionally or unidimensionally measurable indicator lesion
- Hormone receptor status:
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| doxorubicin hydrochlorideAlso: ADM, ADR, Adria, Adriamycin PFS | Drug | Treatment (doxorubicin, cyclophosphamide, tipifarnib, G-CSF) |
| cyclophosphamideAlso: CPM, CTX, Cytoxan, EndoxanGiven IV | Drug | Treatment (doxorubicin, cyclophosphamide, tipifarnib, G-CSF) |
| tipifarnibAlso: R115777, ZarnestraGiven orally | Drug | Treatment (doxorubicin, cyclophosphamide, tipifarnib, G-CSF) |
| filgrastimAlso: G-CSF, NeupogenGiven subcutaneously | Biological | Treatment (doxorubicin, cyclophosphamide, tipifarnib, G-CSF) |
| therapeutic conventional surgeryUndergo complete resection | Procedure or surgery | Treatment (doxorubicin, cyclophosphamide, tipifarnib, G-CSF) |
| laboratory biomarker analysisCorrelative studies | Other | Treatment (doxorubicin, cyclophosphamide, tipifarnib, G-CSF) |
Primary outcome
Pathological complete response in the breast
Time frame: 8 weeks
95% confidence intervals of these estimates will be obtained.
5 secondary outcomes
Proportion of patients who have a clinical complete response
Time frame: 8 weeks
Grade 3 or 4 toxicities assessed using NCI CTCAE version 3.0
Time frame: Up to 5 years
Median disease-free survival
Time frame: Up to 5 years
Percentage of patients free of disease
Time frame: 1 year
Percentage of patients free of disease
Time frame: 2 years
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 6 Jun 2013.
Related trials for Inflammatory Breast Cancer
Active, not recruitingPhase 2
Carboplatin and Paclitaxel Albumin-Stabilized Nanoparticle Formulation Before Surgery in Treating Patients With Locally Advanced or Inflammatory Triple Negative Breast Cancer
Inflammatory Breast Cancer, Stage IIA Breast Cancer
RecruitingObservational study
Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
Rare Disorders, Undiagnosed Disorders
Recruiting
Effects of SPSIP Block on Perioperative Inflammation and TLR4 in Breast Cancer Surgery
Serratus Posterior Superior Intercostal Plane Block (SPSIPB), Breast Cancer
Not yet recruiting
Feasibility and Effectiveness of Sentinel Lymph Node Biopsy in Inflammatory Breast Cancer
Breast Cancer
RecruitingPhase 2
TRUDI: TDXD+Durva in HER2+/Low IBC
Invasive Breast Cancer, Inflammatory Breast Cancer Stage III
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.
Joseph Sparano principal investigator
Albert Einstein College of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing doxorubicin hydrochloride, cyclophosphamide and tipifarnib in people with Inflammatory Breast Cancer and Stage II Breast Cancer, run by National Cancer Institute (NCI) 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 55 inclusion and 0 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 6 Jun 2013. 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 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?
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?
Pathological complete response in the breast (time frame: 8 weeks). 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 6 Jun 2013; AzTrials last refreshed its copy on 8 Nov 2026.