HER2-positive Breast CancerPhase 1NCT00039455
Trastuzumab and Flavopiridol in Treating Patients With Metastatic Breast Cancer
A Phase 1 study testing trastuzumab, alvocidib and laboratory biomarker analysis in people with HER2-positive Breast Cancer and Male Breast Cancer, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HER2-positive Breast Cancer, Male Breast Cancer, Recurrent Breast Cancer
- What is being tested?
- trastuzumab, alvocidib and laboratory biomarker analysis
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2002to Dec 2004
- 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
Who may be able to join
- Patients must have histologically or cytologically confirmed invasive breast cancer, with stage IV disease; patients without pathologic or cytologic confirmation of metastatic disease should have unequivocal evidence of metastasis by physical exam or radiologic study
- Either the primary tumor or the metastasis must overexpress HER2; acceptable methods of measurement of HER2 expression include immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH); tumors tested by IHC must be 3+ positive for HER2 overexpression using the DAKO Herceptest or the CB-11 antibody (recently FDA approved for HER-2 testing); tumors tested by FISH must be positive by either the Vysis Pathyvision method or the Ventana INFORM method; patients may have measurable or evaluable disease
- Patients may have received 0-3 prior chemotherapeutic regimens for metastatic breast cancer
- Patients may have received up to two prior Herceptin-containing regimens in the metastatic setting
- Patients may have received prior radiation therapy in either the metastatic or early stage settings; radiation therapy must be completed at least 7 days prior to study participation
- Patients may have received hormonal therapy (therapies) in the adjuvant or metastatic setting; patients must discontinue hormonal therapy prior to study participation
Show all 18Show fewer
- Life expectancy of greater than 6 months
- ECOG performance status < 2 (Karnofsky > 60%)
- Absolute neutrophil count >= 1,500/mm^3
- Platelets >= 100,000/mm^3
- Total bilirubin =< 1.5 mg/dl
- AST(SGOT)/ALT(SGPT) =< 3 X upper limit normal
- Creatinine =< 2.0 mg/dl
- LVEF >= 50%
- EKG no acute changes
- Patients may not receive concurrent hormonal therapy, chemotherapy, or radiation treatments while on study; patients requiring radiation therapy during protocol-based treatment will be taken off study with the exception of whole brain radiation or stereotactic radiosurgery for brain metastases; protocol-based therapy will be held during the therapy and for 1 week after treatment but may be resumed; patients may not receive other experimental treatments while on study; patient receiving bisphosphonates may continue to receive treatment while on study; patients may initiate bisphosphonate therapy while on study provided that there has been no evidence of progressive disease and that the bone sites do not constitute the only sites of evaluable disease; if patients are on Lupron prior to the start of this trial, than they must continue on Lupron throughout the course of this study
- Patients must be neither pregnant nor expect becoming pregnant or conceiving a child while on study; women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
- Ability to understand and the willingness to sign a written informed consent document
Who cannot join
- Patients who have had more than three chemotherapy regimens in the metastatic setting, more than two Herceptin-containing regimens in the metastatic setting, radiation therapy within 1 week prior to study entry, or those who have not recovered from reversible adverse events due to prior treatments for cancer, are ineligible
- Patients with active brain metastases or leptomengingeal carcinomatosis are excluded from this clinical trial; patients with a history of treated CNS metastases are eligible if they do not have active symptoms from their CNS disease
- Patients with a history of grade 3 or 4 allergic reactions attributed to compounds of similar chemical or biologic composition to the agents used in the study are ineligible; patients who experienced grade 1 or 2 hypersensitivity reactions to prior Herceptin are eligible IF these reactions did not prevent further administration
- Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements are ineligible
- Pregnant women are excluded from this study
- Patients with a contraindication to taking coumadin or other warfarin products are ineligible
Trial locations and contacts
1 site in 1 country.
United States1 site
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
About this study
Official title: A Phase I Study of Herceptin/Flavopiridol in HER-2 Positive Metastatic Breast Cancer
Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining trastuzumab with flavopiridol may kill more tumor cells. Phase I trial to study the effectiveness of combining trastuzumab with flavopiridol in treating patients who have metastatic breast cancer
Read the detailed description
PRIMARY OBJECTIVES:
- To evaluate the safety and tolerability of flavopiridol in combination with Herceptin in HER-2 positive metastatic breast cancer.
SECONDARY OBJECTIVES:
- To determine the dose of flavopiridol necessary to achieve a target plasma level of 300-500 nM of flavopiridol in combination with a fixed dose of Herceptin.
II. To assess the feasibility of measuring cyclin D1 in circulating tumor cells and tissue biopsies before and after therapy as a surrogate marker of flavopiridol activity.
III. To monitor target activity of flavopiridol and Herceptin in plasma, circulating tumor cells and tissue biopsies from breast cancer patients.
OUTLINE: This is a multicenter, dose-escalation study of flavopiridol.
Patients receive trastuzumab (Herceptin) IV over 30-90 minutes on days 1, 8, and 15 followed by flavopiridol IV continuously over 24 hours on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of flavopiridol until the maximum tolerated dose is determined (MTD). 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, an additional cohort of 10 patients receives flavopiridol at the MTD and trastuzumab on the once weekly schedule to assess the true toxicity rate. A second cohort of 10 patients receives flavopiridol at the MTD and trastuzumab once every 21 days to assess the tolerability of this schedule.
PROJECTED ACCRUAL: A total of 30-50 patients will be accrued for this study.
- Conditions
- HER2-positive Breast Cancer, Male Breast Cancer, Recurrent Breast Cancer, Stage IV Breast Cancer
- Being tested
- trastuzumab, alvocidib, laboratory biomarker analysis, pharmacological study
- Medical subject headings
- Breast Neoplasms, Male, Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
trastuzumabBiological
Also called anti-c-erB-2, Herceptin, MOAB HER2
Given IV
alvocidibDrug
Also called FLAVO, flavopiridol, HMR 1275, L-868275
Given IV
laboratory biomarker analysisOther
Correlative studies
Also called pharmacological studies
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (trastuzumab and alvocidib) | Experimental | Patients receive trastuzumab (Herceptin) IV over 30-90 minutes on days 1, 8, and 15 followed by flavopiridol IV continuously over 24 hours on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Receives: Biological: trastuzumab; Drug: alvocidib; Other: laboratory biomarker analysis; Other: pharmacological study |
What is being measured
The primary outcome is the main question the study is designed to answer.
MTD defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity (DLT) assessed using National Cancer Institute (NCI) Common Toxicity Criteria (CTC) version 2.0
Measured: 3 weeks
Secondary outcomes (2)
Measures of circulating extracellular domain of HER-2 in plasma
Descriptive analyses will be performed.
Measured: Up to 3 years
Measures of HER-2, Cyclin D1 and activated Rb in circulating tumor cells
Descriptive analyses will be performed.
Measured: Up to 3 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 startApr 2002
- Primary completionDec 2004
Why it stopped: Administratively complete.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HER2-positive 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Lyndsay Harris, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00039455
- Sponsor's protocol ID
- NCI-2013-00035
- Other IDs
- 01-177, P50CA089393, CDR0000069385
- Status last verified
- Jan 2013
- First submitted
- 6 Jun 2002
- Last updated
- 1 Feb 2013
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Feb 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of Herceptin/Flavopiridol in HER-2 Positive Metastatic Breast Cancer
- ClinicalTrials.gov ID
- NCT00039455
- Acronym / sponsor ID
- NCI-2013-00035
- Conditions
- HER2-positive Breast Cancer, Male Breast Cancer, Recurrent Breast Cancer, Stage IV Breast Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Administratively complete.
- Enrolment
- 50 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Apr 2002
- Primary completion
- Dec 2004 (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.
Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining trastuzumab with flavopiridol may kill more tumor cells. Phase I trial to study the effectiveness of combining trastuzumab with flavopiridol in treating patients who have metastatic breast cancer
Detailed description
PRIMARY OBJECTIVES:
- To evaluate the safety and tolerability of flavopiridol in combination with Herceptin in HER-2 positive metastatic breast cancer.
SECONDARY OBJECTIVES:
- To determine the dose of flavopiridol necessary to achieve a target plasma level of 300-500 nM of flavopiridol in combination with a fixed dose of Herceptin.
II. To assess the feasibility of measuring cyclin D1 in circulating tumor cells and tissue biopsies before and after therapy as a surrogate marker of flavopiridol activity.
III. To monitor target activity of flavopiridol and Herceptin in plasma, circulating tumor cells and tissue biopsies from breast cancer patients.
OUTLINE: This is a multicenter, dose-escalation study of flavopiridol.
Patients receive trastuzumab (Herceptin) IV over 30-90 minutes on days 1, 8, and 15 followed by flavopiridol IV continuously over 24 hours on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of flavopiridol until the maximum tolerated dose is determined (MTD). 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, an additional cohort of 10 patients receives flavopiridol at the MTD and trastuzumab on the once weekly schedule to assess the true toxicity rate. A second cohort of 10 patients receives flavopiridol at the MTD and trastuzumab once every 21 days to assess the tolerability of this schedule.
PROJECTED ACCRUAL: A total of 30-50 patients will be accrued for 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 (trastuzumab and alvocidib) | Experimental | Biological: trastuzumab, Drug: alvocidib, Other: laboratory biomarker analysis, Other: pharmacological studyPatients receive trastuzumab (Herceptin) IV over 30-90 minutes on days 1, 8, and 15 followed by flavopiridol IV continuously over 24 hours on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Patients must have histologically or cytologically confirmed invasive breast cancer, with stage IV disease; patients without pathologic or cytologic confirmation of metastatic disease should have unequivocal evidence of metastasis by physical exam or radiologic study
- Either the primary tumor or the metastasis must overexpress HER2; acceptable methods of measurement of HER2 expression include immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH); tumors tested by IHC must be 3+ positive for HER2 overexpression using the DAKO Herceptest or the CB-11 antibody (recently FDA approved for HER-2 testing); tumors tested by FISH must be positive by either the Vysis Pathyvision method or the Ventana INFORM method; patients may have measurable or evaluable disease
- Patients may have received 0-3 prior chemotherapeutic regimens for metastatic breast cancer
- Patients may have received up to two prior Herceptin-containing regimens in the metastatic setting
- Patients may have received prior radiation therapy in either the metastatic or early stage settings; radiation therapy must be completed at least 7 days prior to study participation
Key exclusion criteria (6 listed)
- Patients who have had more than three chemotherapy regimens in the metastatic setting, more than two Herceptin-containing regimens in the metastatic setting, radiation therapy within 1 week prior to study entry, or those who have not recovered from reversible adverse events due to prior treatments for cancer, are ineligible
- Patients with active brain metastases or leptomengingeal carcinomatosis are excluded from this clinical trial; patients with a history of treated CNS metastases are eligible if they do not have active symptoms from their CNS disease
- Patients with a history of grade 3 or 4 allergic reactions attributed to compounds of similar chemical or biologic composition to the agents used in the study are ineligible; patients who experienced grade 1 or 2 hypersensitivity reactions to prior Herceptin are eligible IF these reactions did not prevent further administration
- Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements are ineligible
- Pregnant women are excluded from this study
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: anti-c-erB-2, Herceptin, MOAB HER2Given IV | Biological | Treatment (trastuzumab and alvocidib) |
| alvocidibAlso: FLAVO, flavopiridol, HMR 1275, L-868275Given IV | Drug | Treatment (trastuzumab and alvocidib) |
| laboratory biomarker analysisCorrelative studies | Other | Treatment (trastuzumab and alvocidib) |
| pharmacological studyAlso: pharmacological studiesCorrelative studies | Other | Treatment (trastuzumab and alvocidib) |
Primary outcome
MTD defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity (DLT) assessed using National Cancer Institute (NCI) Common Toxicity Criteria (CTC) version 2.0
Time frame: 3 weeks
2 secondary outcomes
Measures of circulating extracellular domain of HER-2 in plasma
Time frame: Up to 3 years
Measures of HER-2, Cyclin D1 and activated Rb in circulating tumor cells
Time frame: Up to 3 years
Results and safety
The study was stopped early (reason given: Administratively complete.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Feb 2013.
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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.
Lyndsay Harris principal investigator
Dana-Farber Cancer Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing trastuzumab, alvocidib and laboratory biomarker analysis in people with HER2-positive Breast Cancer and Male 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 18 inclusion and 6 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 1 Feb 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 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 was stopped early (reason given: Administratively complete.). Results are not available in the source record.
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?
MTD defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity (DLT) assessed using National Cancer Institute (NCI) Common Toxicity Criteria (CTC) version 2.0 (time frame: 3 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 1 Feb 2013.