Neoplasms, BreastPhase 1NCT00251433
GW572016 With Docetaxel and Trastuzumab for the Treatment Of Untreated ErbB2 Over-Expressing Metastatic Breast Cancer
A Phase 1 study testing lapatinib, docetaxel, trastuzumab in people with Neoplasms, Breast, run by Novartis Pharmaceuticals at 5 sites in 3 countries.
Trial summary
This study was designed to be two-part study (Phase I/Phase II). Part I was designed to find the optimal (best) doses of GW572016, docetaxel, and trastuzumab when given together. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neoplasms, Breast
- What is being tested?
- lapatinib, docetaxel, trastuzumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 53 participants
- Where
- 5 sitesin 3 countries
- Study dates
- 26 Sep 2005to 22 Jun 2022
- 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
- Subjects must be 18 years of age.
- Criteria for female subjects:
- Non-child-bearing potential (i.e., women with functioning ovaries who have a current documented tubal ligation or hysterectomy, or women who are post- menopausal);
- Child-bearing potential (i.e., women with functioning ovaries and no documented impairment of oviductal or uterine function that would cause sterility.) This category includes women with oligomenorrhoea (severe), women who are perimenopausal, and young women who have begun to menstruate. These subjects must have a negative serum pregnancy test at screening and agree to one of the following:
- Complete abstinence from intercourse from 2 weeks prior to administration of the first dose of study medication until 28 days after the final dose of study medication; or
- Consistent and correct use of one of the following acceptable methods of birth control:
Show all 18Show fewer
- male partner who is sterile prior to the female subject's entry into the study and is the sole sexual partner for that female subject; implants of levonorgestrel; injectable progestogen; any intrauterine device (IUD) with a documented failure rate of less than 1% per year; oral contraceptives (either combined or progestogen only); or barrier methods, including diaphragm or condom with a spermicide.
- Subjects must have an ECOG Performance Status of 0 to 1.
- Subjects must have histologically- or cytologically-confirmed invasive breast cancer with Stage IV disease.
- Subjects must have measurable lesion(s) according to RECIST criteria for phase II, however for phase I subjects evaluable disease will be allowed (including patients with bone lesion only disease).
- Prior to enrolment in the Phase I part of the study, subjects must have documentation of ErbB2 over-expression via IHC3+ or FISH+ testing. Prior to enrolment in the Phase II part of the study, subjects must have ErbB2 over-expression confirmed by a central laboratory,
- Subjects with stable CNS metastases or leptomeningeal involvement are eligible only if they are not taking oral steroids or enzyme-inducing anticonvulsants. Subjects with CNS only disease will not be allowed.
- Subjects that received prior radiotherapy must have completed radiotherapy treatment at least 4 weeks before enrolment and recovered from all treatment-related toxicities.
- Subjects must have new or archived tumour tissue available prior to study entry to evaluate levels of relevant biomarkers.
- Subjects must have a cardiac ejection fraction within the institutional range of normal as measured by Multigated Acquisition (MUGA) scan or echocardiogram (ECHO).
- Subjects must have adequate haematological, hepatic, and renal function. Haemoglobin ≥9gm/dL Absolute granulocyte count ≥1500/mm³ (1.5 x 10^9/L) Platelets ≥75,000/mm³ (75 x 10^9/L) Total bilirubin ≤1.5mg/dL Both ALT and AST ≤1.5 times the upper limit of the normal range (ULN) and alkaline phosphatase ≤2.5 times the ULN (See Taxotere Data Sheet) Serum creatinine ≤ 2.0mg/dL or calculated creatinine clearance (CrCl) ≥40mL/min according to the formula of Cockcroft and Gault
- Subjects who received a taxane as part of adjuvant or neoadjuvant therapy are eligible if they had progression of their disease more than 6 months after completion of treatment.
- Subjects who received prior ErbB inhibitors in the adjuvant setting will be allowed, but a disease-free interval of at least 6 months must be demonstrated after the end of therapy.
Who cannot join
- Subject has peripheral neuropathy of grade 2 or higher;
- Subject has had prior systemic therapy (except one line of hormonal therapy) for metastatic disease. Also, any subjects with prior chemotherapy in the adjuvant or neoadjuvant setting with anthracycline or anthracenedione-containing regimens with cumulative doses of ≥360mg/m² of doxorubicin, ≥720mg/m² of epirubicin, or ≥72mg/m² of mitoxantrone;
- Subjects with prior systemic investigational drugs within the past 30 days or topical investigational drugs within the past 7 days;
- Subjects with uncontrolled or symptomatic angina, arrhythmias, or congestive heart failure;
- Subjects with a known immediate or delayed hypersensitivity or untoward reaction to docetaxel, trastuzumab, or other related compounds, or to drugs chemically related to lapatinib. These include other aminoquinazolines, such as gefitinib (Iressa), erlotinib (Tarceva), or other chemically-related compounds.
- Subjects taking any prohibited medications
- Subject neither affiliated with, nor beneficiary of a social security category (For France only)
Trial locations and contacts
5 sites in 3 countries.
5 sites in 3 countries
France2 sites
Novartis Investigative Site
Paris, 75248
Novartis Investigative Site
Paris, 75475
Ireland2 sites
Novartis Investigative Site
Dublin, 4
Novartis Investigative Site
Dublin, 8
United States1 site
Novartis Investigative Site
Nashville, Tennessee, 37203
About this study
Official title: An Open-label, Multicenter, Phase I/II Dose Escalation Study of Oral GW572016 in Combination With Docetaxel (Taxotere) Plus Trastuzumab (Herceptin) in Subjects Previously Untreated for ErbB2-overexpressing Metastatic Breast Cancer
This study was designed to be two-part study (Phase I/Phase II). Part I was designed to find the optimal (best) doses of GW572016, docetaxel, and trastuzumab when given together. Part II was designed to evaluate the tumor response rate (shrinkage or lack of growth) in patients receiving all three drugs compared to patients receiving only docetaxel and trastuzumab.
Read the detailed description
Phase II part was cancelled before it started. Participants were only enrolled in the phase I part and NOT the phase II part.
- Conditions
- Neoplasms, Breast
- Being tested
- lapatinib, docetaxel, trastuzumab
- Keywords
- ErbB1, ErbB2, trastuzumab (Herceptin), lapatinib, Stage IV breast cancer, metastatic breast cancer, overexpression of ErbB2 receptors, docetaxel (Taxotere)
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
lapatinib, docetaxel, trastuzumabDrug
Also called GW572016
The phase I part of the study will include cohorts of 3 patients to investigate doses of lapatinib (750mg, 1000mg, 1250mg, 1500mg) with 75mg/m2 3- weekly docetaxel plus standard weekly doses of trastuzumab with prophylactic use of growth factors in all patients. Further cohorts may be explored with prophylactic use of growth factors at the doses stipulated in the phase I dose escalation schema
| Study group | Role | What they receive |
|---|---|---|
| Phase I | Experimental | The phase I part of the study will include cohorts of 3 patients to investigate doses of lapatinib (750mg, 1000mg, 1250mg, 1500mg) with 75mg/m2 3- weekly docetaxel plus standard weekly doses of trastuzumab with prophylactic use of growth factors in all patients. Further cohorts may be explored with prophylactic use of growth factors at the doses stipulated in the phase I dose escalation schema Receives: Drug: lapatinib, docetaxel, trastuzumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase I: Optimal doses and toleration of the three drugs administered together.
Measured: 3 weeks
Phase II: The primary efficacy endpoint is objective tumour response rate as measured by radiological imaging, photography, and/or physical examination performed every other cycle and recorded according to RECIST criteria.
Measured: 3 weeks
Secondary outcomes (5)
Phase I and II Tumor response rate; Time to tumor response; Length of response; Time to progression of cancer; Overall survival.
Measured: 6 weeks
PK endpoints: Cmin and Cmax; Concentrations of alpha-1 acid glycoprotein and albumin.
Measured: 6 weeks
Safety and tolerability endpoints will consist of evaluation of AEs and changes from baseline in laboratory values.
Measured: 6 weeks
Relevant biomarkers, including ErbB1, ErbB2, ErbB3, ErbB4, AKT, and potentially other biomarkers downstream from the ErbB1 and ErbB2 receptors, will be determined from tumour tissue.
Measured: 6 weeks
Serum concentrations of ErbB1 and ErbB2 ECD will be correlated to tumour response.
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Nov 2005 (estimated)
- Study start26 Sep 2005
- Primary completion10 Jun 2010
- Study completion22 Jun 2022
Why it stopped: EGF100161 (NCT00251433) was terminated in Phase I (Phase II expansion portion of the study was never initiated) by sponsor decision.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Neoplasms, BreastStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 53 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00251433
- Sponsor's protocol ID
- EGF100161
- Other IDs
- 2005-000846-35, CLAP016A2101, 2005
- Status last verified
- Mar 2023
- First submitted
- 8 Nov 2005
- Last updated
- 31 Mar 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Crown J, Kennedy MJ, Tresca P, Marty M, Espie M, Burris HA, DeSilvio M, Lau MR, Kothari D, Koch KM, Dieras V. Optimally tolerated dose of lapatinib in combination with docetaxel plus trastuzumab in first-line treatment of HER2-positive metastatic breast cancer. Ann Oncol. 2013 Aug;24(8):2005-11. doi: 10.1093/annonc/mdt222.
PubMed 23878115
Study at a glance
From the registry record, last updated by the sponsor on 31 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Multicenter, Phase I/II Dose Escalation Study of Oral GW572016 in Combination With Docetaxel (Taxotere) Plus Trastuzumab (Herceptin) in Subjects Previously Untreated for ErbB2-overexpressing Metastatic Breast Cancer
- ClinicalTrials.gov ID
- NCT00251433
- Acronym / sponsor ID
- EGF100161
- Conditions
- Neoplasms, Breast
- Keywords
- ErbB1, ErbB2, trastuzumab (Herceptin), lapatinib, Stage IV breast cancer, metastatic breast cancer, overexpression of ErbB2 receptors, docetaxel (Taxotere)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: EGF100161 (NCT00251433) was terminated in Phase I (Phase II expansion portion of the study was never initiated) by sponsor decision.
- Enrolment
- 53 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 26 Sep 2005 (actual)
- Primary completion
- 10 Jun 2010 (actual)
- Study completion
- 22 Jun 2022 (actual)
- First posted
- 10 Nov 2005 (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.
This study was designed to be two-part study (Phase I/Phase II). Part I was designed to find the optimal (best) doses of GW572016, docetaxel, and trastuzumab when given together. Part II was designed to evaluate the tumor response rate (shrinkage or lack of growth) in patients receiving all three drugs compared to patients receiving only docetaxel and trastuzumab.
Detailed description
Phase II part was cancelled before it started. Participants were only enrolled in the phase I part and NOT the phase II part.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Phase I | Experimental | Drug: lapatinib, docetaxel, trastuzumabThe phase I part of the study will include cohorts of 3 patients to investigate doses of lapatinib (750mg, 1000mg, 1250mg, 1500mg) with 75mg/m2 3- weekly docetaxel plus standard weekly doses of trastuzumab with prophylactic use of growth factors in all patients. Further cohorts may be explored with prophylactic use of growth factors at the doses stipulated in the phase I dose escalation schema |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Subjects must be 18 years of age.
- Non-child-bearing potential (i.e., women with functioning ovaries who have a current documented tubal ligation or hysterectomy, or women who are post- menopausal);
- Child-bearing potential (i.e., women with functioning ovaries and no documented impairment of oviductal or uterine function that would cause sterility.) This category includes women with oligomenorrhoea (severe), women who are perimenopausal, and young women who have begun to menstruate. These subjects must have a negative serum pregnancy test at screening and agree to one of the following:
- Complete abstinence from intercourse from 2 weeks prior to administration of the first dose of study medication until 28 days after the final dose of study medication; or
- Consistent and correct use of one of the following acceptable methods of birth control:
Key exclusion criteria (7 listed)
- Subject has peripheral neuropathy of grade 2 or higher;
- Subject has had prior systemic therapy (except one line of hormonal therapy) for metastatic disease. Also, any subjects with prior chemotherapy in the adjuvant or neoadjuvant setting with anthracycline or anthracenedione-containing regimens with cumulative doses of ≥360mg/m² of doxorubicin, ≥720mg/m² of epirubicin, or ≥72mg/m² of mitoxantrone;
- Subjects with prior systemic investigational drugs within the past 30 days or topical investigational drugs within the past 7 days;
- Subjects with uncontrolled or symptomatic angina, arrhythmias, or congestive heart failure;
- Subjects with a known immediate or delayed hypersensitivity or untoward reaction to docetaxel, trastuzumab, or other related compounds, or to drugs chemically related to lapatinib. These include other aminoquinazolines, such as gefitinib (Iressa), erlotinib (Tarceva), or other chemically-related compounds.
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 |
|---|---|---|
| lapatinib, docetaxel, trastuzumabAlso: GW572016The phase I part of the study will include cohorts of 3 patients to investigate doses of lapatinib (750mg, 1000mg, 1250mg, 1500mg) with 75mg/m2 3- weekly docetaxel plus standard weekly doses of trastuzumab with prophylactic use of growth factors in all patients. Further cohorts may be explored with prophylactic use of growth factors at the doses stipulated in the phase I dose escalation schema | Drug | Phase I |
Primary outcome
Phase I: Optimal doses and toleration of the three drugs administered together.
Time frame: 3 weeks
Phase II: The primary efficacy endpoint is objective tumour response rate as measured by radiological imaging, photography, and/or physical examination performed every other cycle and recorded according to RECIST criteria.
Time frame: 3 weeks
5 secondary outcomes
Phase I and II Tumor response rate; Time to tumor response; Length of response; Time to progression of cancer; Overall survival.
Time frame: 6 weeks
PK endpoints: Cmin and Cmax; Concentrations of alpha-1 acid glycoprotein and albumin.
Time frame: 6 weeks
Safety and tolerability endpoints will consist of evaluation of AEs and changes from baseline in laboratory values.
Time frame: 6 weeks
Relevant biomarkers, including ErbB1, ErbB2, ErbB3, ErbB4, AKT, and potentially other biomarkers downstream from the ErbB1 and ErbB2 receptors, will be determined from tumour tissue.
Time frame: 6 weeks
Serum concentrations of ErbB1 and ErbB2 ECD will be correlated to tumour response.
Time frame: 6 weeks
Results and safety
The study was stopped early (reason given: EGF100161 (NCT00251433) was terminated in Phase I (Phase II expansion portion of the study was never initiated) by sponsor decision.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Mar 2023.
- Results publication: PubMed 23878115Crown J, Kennedy MJ, Tresca P, Marty M, Espie M, Burris HA, DeSilvio M, Lau MR, Kothari D, Koch KM, Dieras V. Optimally tolerated dose of lapatinib in combination with docetaxel plus trastuzumab in first-line treatment of HER2-positive metastatic breast cancer. Ann Oncol. 2013 Aug;24(8):2005-11. doi: 10.1093/annonc/mdt222.
- Related InfoLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
5 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 lapatinib, docetaxel, trastuzumab in people with Neoplasms, Breast, run by Novartis Pharmaceuticals at 5 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?
The sponsor lists 18 inclusion and 7 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 31 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in France, Ireland, 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: EGF100161 (NCT00251433) was terminated in Phase I (Phase II expansion portion of the study was never initiated) by sponsor decision.). 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?
Phase I: Optimal doses and toleration of the three drugs administered together. (time frame: 3 weeks). The study lists 2 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 NCT00251433, which also lists 1 linked publication.
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 31 Mar 2023.