Metastatic Breast Cancer With Intracranial MetastasesPhase 2NCT01934894
Cabazitaxel Plus Lapatinib as Therapy for HER2-Positive Metastatic Breast Cancer Patients With Intracranial Metastases
A Phase 2 study testing cabazitaxel and lapatinib in people with Metastatic Breast Cancer With Intracranial Metastases, run by SCRI Development Innovations, LLC at 4 sites in United States.
Trial summary
This phase II trial will combine two agents, cabazitaxel and lapatinib, to treat patients with metastatic breast cancer (MBC) which has metastasized to the brain. The first portion of the study will determine the optimal dose of the cabazitaxel/lapatinib combination to administer to patients. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Breast Cancer With Intracranial Metastases
- What is being tested?
- cabazitaxel and lapatinib
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 4 sitesUnited States
- Study dates
- May 2014to Apr 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with HER2-positive MBC and unequivocal evidence of brain metastases.
- Documented HER2-positive tumor status at study entry defined as:
- Immunohistochemical (IHC) score 3+ or
- IHC score 1-2+ and confirmed as FISH (Fluorescence in situ hybridization) positive (based on ASCO-CAP guidelines 2013) or
- FISH or ISH (in situ hybridization) positive (based on ASCO-CAP guidelines 2013)
- Patient must have at least one measurable brain lesion (defined as any lesion ≥ 5mm cm in the longest dimension), on T1 weighted, gadolinium enhanced MRI. Patients may have had surgical excisions of brain metastases provided at least one lesions meets the following criteria:
Show all 35Show fewer
- Patients with brain metastases previously untreated with any intra-cranial radiation (i.e. no whole brain radiation therapy [WBRT]/partial brain radiation or stereotactic radiosurgery [SRS]) must have at least one intra-cranial tumor lesion that is ≥ 5mm.
- Patients with brain metastases previously untreated with any intracranial radiation (i.e., no whole brain radiation therapy [WBRT]/partial brain radiation or stereotactic radiosurgery [SRS]) must have at least one intracranial tumor lesion that is ≥ 5mm.
- Patients with brain metastases previously treated with WBRT/partial brain radiation only must have at least one intracranial tumor lesion ≥ 5mm and must have evidence of intracranial progressive disease
- Patients previously treated with WBRT/partial brain radiation and SRS must have at least one intracranial tumor lesion ≥ 5mm that was not treated with SRS and must have intracranial disease.
- Patients previously treated with SRS must either demonstrate disease progression ≥ 12 weeks after completing SRS with a lesion measuring ≥ 5mm or must have at least one intracranial tumor lesion ≥ 5mm that was not treated with SRS.
- Patients who have received WBRT/partial brain radiation for intra-cranial metastases are eligible if treatment was completed ≥28 days prior to the first dose of study drug.
- Estrogen receptor (ER) and progesterone receptor (PR) status in the primary or most recent tumor assessment must be known or pending at the time of study registration. Patient's ER/PR status (i.e., positive or negative) does not influence enrollment but is a requirement.
- Patient must have received prior treatment with HER2-directed therapy such as trastuzumab, either in the adjuvant or metastatic setting.
- Prior treatment with lapatinib in the (neo)adjuvant and metastatic setting.
- Patients without prior chemotherapy for MBC are eligible provided the patients relapsed during adjuvant therapy with trastuzumab or ≤6 months following completion of adjuvant therapy. Otherwise, there is no specific minimum or maximum number of previous chemotherapy regimens for MBC.
- Patients must have completed cytotoxic chemotherapy ≥21 days (for an every 3-week regimen) or ≥14 days (for an every 2-week or weekly regimen) and have recovered from or come to a new chronic or stable baseline from all treatment-related toxicities in order to be eligible for study treatment.
- Patient must have completed biologic therapy ≥3 weeks or 5-half lives whichever is shorter.
- Patient must be discontinued from hormonal therapy a minimum of 1 day prior to the first dose of study treatment.
- Patients receiving palliative radiation to bone, soft tissue or any other disease sites must have completed this ≥1 week prior to the first dose of study treatment.
- Patients must have recovered (>2 week recovery is mandated) from any acute neurosurgical intervention for metastatic CNS disease (e.g., resection, shunt placement) and must be clinically stable. These patients must have residual measurable CNS lesion(s) following the surgical procedure if this site is to serve as the target lesion.
- Patients must be neurologically stable, and if receiving steroids, must be on stable or decreasing doses of corticosteroids and/or anticonvulsants for defined as being on stable low doses of corticosteroids ≥ 5 days prior to the first dose of study treatment.
- Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 to 2.
- Adequate hematologic, renal, and hepatic function.
- Adequate coagulation parameters.
- Other laboratory testing:
- Serum magnesium ≥ the institutional lower limit of normal (LLN)
- Serum potassium ≥ the institutional LLN
- Left-ventricular-ejection fraction (LVEF) of ≥50% by an echocardiogram (ECHO) or by a multiple-gated acquisition (MUGA)
- Male patients willing to use adequate contraceptive measures.
- Female patients who are not of child-bearing potential, and female patients of child-bearing potential who agree to use adequate contraceptive measures, who are not breastfeeding, and who have a negative serum or urine pregnancy test within 72 hours prior to start of treatment.
- Life expectancy ≥12 weeks.
- Ability to swallow oral medications.
- Willingness and ability to comply with trial and follow-up procedures.
- Ability to understand the nature of this trial and give written informed consent.
Who cannot join
- Previous treatment with cabazitaxel.
- CNS disease requiring immediate neurosurgical intervention (e.g., resection, shunt placement, etc.).
- Leptomeningeal metastases as the only site of CNS metastases. Patients with parenchymal brain metastases and leptomeningeal metastases are eligible provided they meet all other eligibility criteria.
- Peripheral neuropathy ≥Grade 2 (CTCAE v4.0).
- Concurrent treatment with radiation therapy, hormonal therapy, biologic therapy or chemotherapy is not allowed. Low dose corticosteroids (≤30 mg/day prednisone or its equivalent) are allowed.
- Concurrent treatment with drugs known to be moderate and strong inhibitors or inducers of isoenzyme CYP3A that cannot be discontinued or switched to different medication prior to starting study drug.
Show all 19Show fewer
- Concurrent use of St. John's wort and grapefruit/grapefruit juice ≤7 days prior to starting study drug is not allowed.
- Presence of active gastrointestinal (GI) disease or other condition that in the opinion of the investigator will interfere significantly with the absorption, distribution, metabolism, or excretion of oral therapy (e.g. ulcerative disease, uncontrolled nausea, or vomiting).
- Known diagnosis of human immunodeficiency virus (HIV), Hepatitis B (HBV) or Hepatitis C (HCV).
- Presence of other active cancers, or history of treatment for invasive cancer ≥3 years. Patients with stage I cancer who have received definitive local treatment with curative intent at least 3 years previously, and are considered unlikely to recur are eligible. All patients with previously treated in situ carcinoma (i.e. non-invasive) are eligible, as are patients with history of non-melanoma skin cancer.
- Any severe and/or uncontrolled medical conditions or other conditions that could affect participation in the study such as:
- Symptomatic congestive heart failure (CHF) of New York Heart Association Class III or IV.
- QTc > 480 ms on screening ECG (using the Fredericia formula)
- Poorly controlled or clinically significant atherosclerotic vascular disease including cerebrovascular accident (CVA), transient ischemic attack (TIA), angioplasty, cardiac or vascular stenting in the past 6 months
- Active (acute or chronic) or uncontrolled severe infections.
- Active hepatic or biliary disease (except for patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases, or stable chronic liver disease per investigator assessment).
- Known hypersensitivity to cabazitaxel or other drugs formulated with polysorbate 80.
- Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.
- Inability or unwillingness to comply with study and/or follow-up procedures outlined in the protocol.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Oncology Hematology Care Inc.
Cincinnati, Ohio, 45242
Florida Cancer Specialists - South
Fort Myers, Florida, 33916
Tennessee Oncology
Nashville, Tennessee, 37203
Florida Cancer Specialists-North
St. Petersburg, Florida, 33705
About this study
Official title: Phase II Study With Lead-in Safety Cohort of Cabazitaxel Plus Lapatinib as Therapy for HER2-Positive Metastatic Breast Cancer Patients With Intracranial Metastases
This phase II trial will combine two agents, cabazitaxel and lapatinib, to treat patients with metastatic breast cancer (MBC) which has metastasized to the brain. The first portion of the study will determine the optimal dose of the cabazitaxel/lapatinib combination to administer to patients. After determining the optimal dose, patients will continue treatment with cabazitaxel and lapatinib to assess response to treatment with these agents.
Read the detailed description
This is an open-label, non-randomized, Phase II study with a lead-in safety cohort. Through the safety lead-in portion of this trial we will define the optimal dose of cabazitaxel when given in combination with lapatinib for patients with HER2-positive MBC and CNS metastases. The Phase II portion will further assess intracranial response rate in patients with HER2-positive MBC and CNS metastases. Toxicity and progression free survival (PFS) will be obtained and evaluated. The trial will be conducted at multiple study sites by SCRI Development Innovations.
- Being tested
- cabazitaxel, lapatinib
- Keywords
- HER2-positive breast cancer, intracranial metastases, lapatinib, cabazitaxel
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cabazitaxelDrug
Also called Jevtana, XRP6258
lapatinibDrug
Also called Tykerb, GW572016
| Study group | Role | What they receive |
|---|---|---|
| cabazitaxel and lapatinib combination | Experimental | * Cabazitaxel 1-hour IV infusion on Day 1 of each 3 week cycle (dose to be determined)
* Lapatinib PO once daily (dose to be determined)
Treatment cycles will be repeated every 3 weeks. Receives: Drug: cabazitaxel; Drug: lapatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
CNS Objective Response
The number of patients with Complete and Partial Response (CR+PR) of CNS lesions assessed per modified RECIST Criteria for Evaluation of Intracranial Disease. CR=disappearance of all target and non-target lesions; PR=at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter AND an absolute decrease of at least 5mm in at least one target lesion.
Measured: every 6 weeks thru cycle 8, then every 9 weeks until treatment discontinuation, projected 1 year
Maximum Tolerated Dose of Cabazitaxel With Lapatinib
The maximum tolerated dose (MTD) of cabazitaxel and lapatinib will be determined as the highest dose at which ≤1 of 6 patients experiences a dose-limiting toxicity (DLT) assessed according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0. A listing of DLTs are reported in the subsequent Primary Outcome Measure.
Measured: weekly for 3 weeks
Number of Participants Who Experience Dose-Limiting Toxicities (DLTs) as a Measure of Safety
During the safety lead-in, a standard 3+3 dose escalation design is used to determine the maximum tolerated dose (MTD) of cabazitaxel with lapatinib. The MTD would be determined by the highest dose at which ≤1 of 6 patients experiences a dose-limiting toxicity (DLT) during 1 cycle (21 days) of therapy. If 2 of 6 patients within a dose level experiences a DLT, that dose level would be defined as exceeding the MTD and the previous dose level would be evaluated. DLTs are assessed according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0.
Measured: weekly for 3 weeks
Secondary outcomes (3)
CNS Clinical Benefit Response
The number of patients with Complete Response, Partial Response or Stable Disease extending beyond 6 months (CR+PR+SD ≥ 6 months), determined by RECIST v1.1. CR=disappearance of all target and non-target lesions; PR=at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter AND an absolute decrease of at least 5mm in at least one target lesion; SD=Neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum of the longest diameter since the treatment started.
Measured: every 6 weeks thru cycle 8, and every 3 cycles thereafter until treatment discontinuation, projected 1 year
Extra-Cranial Objective Response
The number of participants having Complete and Partial Responses (CR+PR) of extra-cranial lesions assessed per RECIST v1.1 Criteria. CR=disappearance of all target and non-target lesions; PR=at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter AND an absolute decrease of at least 5mm in at least one target lesion.
Measured: every 6 weeks for 8 cycles, then every 9 weeks until treatment discontinuation, up to 1 year
CNS Progression Free Survival
Evaluate the three and six-month CNS progression free survival measured from date of first protocol treatment until tumor progression or death.
Measured: every 6 weeks thru cycle 8, then every 9 weeks until treatment discontinuation, projected 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Sep 2013 (estimated)
- Study startMay 2014
- Primary completionFeb 2016
- Study completionApr 2017
Why it stopped: Study was terminated due to lack of significant signal of efficacy
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.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Metastatic Breast Cancer With Intracranial MetastasesStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- SCRI Development Innovations, LLC
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis, GlaxoSmithKline, Sanofi
- Responsible party
- Sponsor
- Investigators
- Denise A. Yardley, MD, Study chair, SCRI Development Innovations
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01934894
- Sponsor's protocol ID
- SCRI BRE 200
- Status last verified
- Jun 2017
- First submitted
- 27 Aug 2013
- Last updated
- 2 Jul 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Cisternino S, Bourasset F, Archimbaud Y, Semiond D, Sanderink G, Scherrmann JM. Nonlinear accumulation in the brain of the new taxoid TXD258 following saturation of P-glycoprotein at the blood-brain barrier in mice and rats. Br J Pharmacol. 2003 Apr;138(7):1367-75. doi: 10.1038/sj.bjp.0705150.
PubMed 12711638Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.
PubMed 19097774Geyer CE, Forster J, Lindquist D, Chan S, Romieu CG, Pienkowski T, Jagiello-Gruszfeld A, Crown J, Chan A, Kaufman B, Skarlos D, Campone M, Davidson N, Berger M, Oliva C, Rubin SD, Stein S, Cameron D. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med. 2006 Dec 28;355(26):2733-43. doi: 10.1056/NEJMoa064320.
PubMed 17192538Lin NU, Winer EP. Brain metastases: the HER2 paradigm. Clin Cancer Res. 2007 Mar 15;13(6):1648-55. doi: 10.1158/1078-0432.CCR-06-2478.
PubMed 17363517Lin NU, Carey LA, Liu MC, Younger J, Come SE, Ewend M, Harris GJ, Bullitt E, Van den Abbeele AD, Henson JW, Li X, Gelman R, Burstein HJ, Kasparian E, Kirsch DG, Crawford A, Hochberg F, Winer EP. Phase II trial of lapatinib for brain metastases in patients with human epidermal growth factor receptor 2-positive breast cancer. J Clin Oncol. 2008 Apr 20;26(12):1993-9. doi: 10.1200/JCO.2007.12.3588.
PubMed 18421051Lin NU, Dieras V, Paul D, Lossignol D, Christodoulou C, Stemmler HJ, Roche H, Liu MC, Greil R, Ciruelos E, Loibl S, Gori S, Wardley A, Yardley D, Brufsky A, Blum JL, Rubin SD, Dharan B, Steplewski K, Zembryki D, Oliva C, Roychowdhury D, Paoletti P, Winer EP. Multicenter phase II study of lapatinib in patients with brain metastases from HER2-positive breast cancer. Clin Cancer Res. 2009 Feb 15;15(4):1452-9. doi: 10.1158/1078-0432.CCR-08-1080.
PubMed 19228746Pivot X, Koralewski P, Hidalgo JL, Chan A, Goncalves A, Schwartsmann G, Assadourian S, Lotz JP. A multicenter phase II study of XRP6258 administered as a 1-h i.v. infusion every 3 weeks in taxane-resistant metastatic breast cancer patients. Ann Oncol. 2008 Sep;19(9):1547-52. doi: 10.1093/annonc/mdn171. Epub 2008 Apr 23.
PubMed 18436520Villanueva C, Awada A, Campone M, Machiels JP, Besse T, Magherini E, Dubin F, Semiond D, Pivot X. A multicentre dose-escalating study of cabazitaxel (XRP6258) in combination with capecitabine in patients with metastatic breast cancer progressing after anthracycline and taxane treatment: a phase I/II study. Eur J Cancer. 2011 May;47(7):1037-45. doi: 10.1016/j.ejca.2011.01.001. Epub 2011 Feb 19.
PubMed 21339064Yardley DA, Hart LL, Ward PJ, Wright GL, Shastry M, Finney L, DeBusk LM, Hainsworth JD. Cabazitaxel Plus Lapatinib as Therapy for HER2+ Metastatic Breast Cancer With Intracranial Metastases: Results of a Dose-finding Study. Clin Breast Cancer. 2018 Oct;18(5):e781-e787. doi: 10.1016/j.clbc.2018.03.004. Epub 2018 Mar 8.
PubMed 29678476
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study With Lead-in Safety Cohort of Cabazitaxel Plus Lapatinib as Therapy for HER2-Positive Metastatic Breast Cancer Patients With Intracranial Metastases
- ClinicalTrials.gov ID
- NCT01934894
- Acronym / sponsor ID
- SCRI BRE 200
- Keywords
- HER2-positive breast cancer, intracranial metastases, lapatinib, cabazitaxel
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study was terminated due to lack of significant signal of efficacy
- Enrolment
- 11 participants (actual)
- Lead sponsor
- SCRI Development Innovations, LLCUniversity, hospital or other
- Collaborators
- Novartis, GlaxoSmithKline, Sanofi
- Study start
- May 2014 (actual)
- Primary completion
- Feb 2016 (actual)
- Study completion
- Apr 2017 (actual)
- First posted
- 4 Sep 2013 (estimated)
- Results
- Posted 2 Jun 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II trial will combine two agents, cabazitaxel and lapatinib, to treat patients with metastatic breast cancer (MBC) which has metastasized to the brain. The first portion of the study will determine the optimal dose of the cabazitaxel/lapatinib combination to administer to patients. After determining the optimal dose, patients will continue treatment with cabazitaxel and lapatinib to assess response to treatment with these agents.
Detailed description
This is an open-label, non-randomized, Phase II study with a lead-in safety cohort. Through the safety lead-in portion of this trial we will define the optimal dose of cabazitaxel when given in combination with lapatinib for patients with HER2-positive MBC and CNS metastases. The Phase II portion will further assess intracranial response rate in patients with HER2-positive MBC and CNS metastases. Toxicity and progression free survival (PFS) will be obtained and evaluated. The trial will be conducted at multiple study sites by SCRI Development Innovations.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| cabazitaxel and lapatinib combination | Experimental | Drug: cabazitaxel, Drug: lapatinib* Cabazitaxel 1-hour IV infusion on Day 1 of each 3 week cycle (dose to be determined) * Lapatinib PO once daily (dose to be determined) Treatment cycles will be repeated every 3 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (35 listed)
- Patients with HER2-positive MBC and unequivocal evidence of brain metastases.
- Documented HER2-positive tumor status at study entry defined as:
- Patient must have at least one measurable brain lesion (defined as any lesion ≥ 5mm cm in the longest dimension), on T1 weighted, gadolinium enhanced MRI. Patients may have had surgical excisions of brain metastases provided at least one lesions meets the following criteria:
- Patients who have received WBRT/partial brain radiation for intra-cranial metastases are eligible if treatment was completed ≥28 days prior to the first dose of study drug.
- Estrogen receptor (ER) and progesterone receptor (PR) status in the primary or most recent tumor assessment must be known or pending at the time of study registration. Patient's ER/PR status (i.e., positive or negative) does not influence enrollment but is a requirement.
Key exclusion criteria (19 listed)
- Previous treatment with cabazitaxel.
- CNS disease requiring immediate neurosurgical intervention (e.g., resection, shunt placement, etc.).
- Leptomeningeal metastases as the only site of CNS metastases. Patients with parenchymal brain metastases and leptomeningeal metastases are eligible provided they meet all other eligibility criteria.
- Peripheral neuropathy ≥Grade 2 (CTCAE v4.0).
- Concurrent treatment with radiation therapy, hormonal therapy, biologic therapy or chemotherapy is not allowed. Low dose corticosteroids (≤30 mg/day prednisone or its equivalent) are allowed.
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 |
|---|---|---|
| cabazitaxelAlso: Jevtana, XRP6258 | Drug | cabazitaxel and lapatinib combination |
| lapatinibAlso: Tykerb, GW572016 | Drug | cabazitaxel and lapatinib combination |
Primary outcome
CNS Objective Response
Time frame: every 6 weeks thru cycle 8, then every 9 weeks until treatment discontinuation, projected 1 year
The number of patients with Complete and Partial Response (CR+PR) of CNS lesions assessed per modified RECIST Criteria for Evaluation of Intracranial Disease. CR=disappearance of all target and non-target lesions; PR=at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter AND an absolute decrease of at least 5mm in at least one target lesion.
Maximum Tolerated Dose of Cabazitaxel With Lapatinib
Time frame: weekly for 3 weeks
The maximum tolerated dose (MTD) of cabazitaxel and lapatinib will be determined as the highest dose at which ≤1 of 6 patients experiences a dose-limiting toxicity (DLT) assessed according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0. A listing of DLTs are reported in the subsequent Primary Outcome Measure.
Number of Participants Who Experience Dose-Limiting Toxicities (DLTs) as a Measure of Safety
Time frame: weekly for 3 weeks
During the safety lead-in, a standard 3+3 dose escalation design is used to determine the maximum tolerated dose (MTD) of cabazitaxel with lapatinib. The MTD would be determined by the highest dose at which ≤1 of 6 patients experiences a dose-limiting toxicity (DLT) during 1 cycle (21 days) of therapy. If 2 of 6 patients within a dose level experiences a DLT, that dose level would be defined as exceeding the MTD and the previous dose level would be evaluated. DLTs are assessed according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0.
3 secondary outcomes
CNS Clinical Benefit Response
Time frame: every 6 weeks thru cycle 8, and every 3 cycles thereafter until treatment discontinuation, projected 1 year
Extra-Cranial Objective Response
Time frame: every 6 weeks for 8 cycles, then every 9 weeks until treatment discontinuation, up to 1 year
CNS Progression Free Survival
Time frame: every 6 weeks thru cycle 8, then every 9 weeks until treatment discontinuation, projected 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 12711638Cisternino S, Bourasset F, Archimbaud Y, Semiond D, Sanderink G, Scherrmann JM. Nonlinear accumulation in the brain of the new taxoid TXD258 following saturation of P-glycoprotein at the blood-brain barrier in mice and rats. Br J Pharmacol. 2003 Apr;138(7):1367-75. doi: 10.1038/sj.bjp.0705150.
- Background: PubMed 19097774Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.
- Background: PubMed 17192538Geyer CE, Forster J, Lindquist D, Chan S, Romieu CG, Pienkowski T, Jagiello-Gruszfeld A, Crown J, Chan A, Kaufman B, Skarlos D, Campone M, Davidson N, Berger M, Oliva C, Rubin SD, Stein S, Cameron D. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med. 2006 Dec 28;355(26):2733-43. doi: 10.1056/NEJMoa064320.
- Background: PubMed 17363517Lin NU, Winer EP. Brain metastases: the HER2 paradigm. Clin Cancer Res. 2007 Mar 15;13(6):1648-55. doi: 10.1158/1078-0432.CCR-06-2478.
- Background: PubMed 18421051Lin NU, Carey LA, Liu MC, Younger J, Come SE, Ewend M, Harris GJ, Bullitt E, Van den Abbeele AD, Henson JW, Li X, Gelman R, Burstein HJ, Kasparian E, Kirsch DG, Crawford A, Hochberg F, Winer EP. Phase II trial of lapatinib for brain metastases in patients with human epidermal growth factor receptor 2-positive breast cancer. J Clin Oncol. 2008 Apr 20;26(12):1993-9. doi: 10.1200/JCO.2007.12.3588.
- Background: PubMed 19228746Lin NU, Dieras V, Paul D, Lossignol D, Christodoulou C, Stemmler HJ, Roche H, Liu MC, Greil R, Ciruelos E, Loibl S, Gori S, Wardley A, Yardley D, Brufsky A, Blum JL, Rubin SD, Dharan B, Steplewski K, Zembryki D, Oliva C, Roychowdhury D, Paoletti P, Winer EP. Multicenter phase II study of lapatinib in patients with brain metastases from HER2-positive breast cancer. Clin Cancer Res. 2009 Feb 15;15(4):1452-9. doi: 10.1158/1078-0432.CCR-08-1080.
- Background: PubMed 18436520Pivot X, Koralewski P, Hidalgo JL, Chan A, Goncalves A, Schwartsmann G, Assadourian S, Lotz JP. A multicenter phase II study of XRP6258 administered as a 1-h i.v. infusion every 3 weeks in taxane-resistant metastatic breast cancer patients. Ann Oncol. 2008 Sep;19(9):1547-52. doi: 10.1093/annonc/mdn171. Epub 2008 Apr 23.
- Background: PubMed 21339064Villanueva C, Awada A, Campone M, Machiels JP, Besse T, Magherini E, Dubin F, Semiond D, Pivot X. A multicentre dose-escalating study of cabazitaxel (XRP6258) in combination with capecitabine in patients with metastatic breast cancer progressing after anthracycline and taxane treatment: a phase I/II study. Eur J Cancer. 2011 May;47(7):1037-45. doi: 10.1016/j.ejca.2011.01.001. Epub 2011 Feb 19.
- Derived from this study: PubMed 29678476Yardley DA, Hart LL, Ward PJ, Wright GL, Shastry M, Finney L, DeBusk LM, Hainsworth JD. Cabazitaxel Plus Lapatinib as Therapy for HER2+ Metastatic Breast Cancer With Intracranial Metastases: Results of a Dose-finding Study. Clin Breast Cancer. 2018 Oct;18(5):e781-e787. doi: 10.1016/j.clbc.2018.03.004. Epub 2018 Mar 8.
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TNBC - Triple-Negative Breast Cancer, Triple Negative Breast Cancer
Recruiting
SILibinin in NSCLC and BC Patients With Single Brain METastasis (SILMET)
Brain Metastases, Adult, Non Small Cell Lung Cancer
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.
Denise A. Yardley, MD study chair
SCRI Development Innovations
4 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 cabazitaxel and lapatinib in people with Metastatic Breast Cancer With Intracranial Metastases, run by SCRI Development Innovations, LLC at 4 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 35 inclusion and 19 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 2 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 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. 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 2 Jun 2017). 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?
CNS Objective Response (time frame: every 6 weeks thru cycle 8, then every 9 weeks until treatment discontinuation, projected 1 year). The study lists 3 primary outcomes in all. 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 NCT01934894, which also lists 9 linked publications.
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 2 Jul 2017.