A Phase 2 interventional study of GW572016 and lapatinib in Breast Cancer, sponsored by Baylor Breast Care Center. Completed at 3 sites in United States. Open to female participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2021-09-29.
Sponsored by Baylor Breast Care Center · Phase 2, Interventional, and Treatment
Among 114 studies testing lapatinib in Breast Neoplasms — none open to participants now, 3 under way, 1 of them phase 3. Lapatinib · Breast Neoplasms.
Among the 114 studies testing lapatinib in Breast Neoplasms, this one is the 47th largest by enrollment, is one of 9 that started in 2004, is one of 60 in phase 2, and was the 11th registered.
14,825 studies on the registry are indexed under Breast Neoplasms; 3,319 are open to participants now.
This study's enrollment of 49 is below the median of 72 across 10,896 interventional studies indexed under Breast Neoplasms.
Browse Breast Neoplasms studies →None of the 114 studies testing lapatinib in Breast Neoplasms is open now.
Lapatinib: first FDA approval 2007 (TYKERB), first EMA approval 2008. What it is approved for, and how studies give it, is on its page →
Of the 2,400 Breast Neoplasms studies recruiting now, 1,572 (66%) set no upper age limit and 591 (25%) stop at 75 or younger; 103 take children under 18; 214 take healthy volunteers.
This study: 18 Years and older · female · no healthy volunteers.
The full table on the hub →114 studies; the count open now beside each. This study's row is marked.
First in 2003; this study’s year is marked. 9 started in 2004.
Median enrollment 35 across the 114 interventional studies. Of the 99 that completed or were terminated, 50 (51%) have results posted.
48 of 114 have an industry lead sponsor. The 10 most frequent:
Baylor Breast Care Center is the lead sponsor of 16 studies on the registry; 1 is open to participants now.
16 studies in Breast Neoplasms by Baylor Breast Care Center: 1 open now, 3 under way, none of them phase 3. Of 12 finished, 6 (50%) have results posted.
Among the 16 studies in Breast Neoplasms by Baylor Breast Care Center, this one is the 6th largest by enrollment, is the only one that started in 2004, is one of 13 in phase 2, and was the 5th registered.
Baylor Breast Care Center’s Breast Neoplasms studies by the year they started, since 1999.
None of the studies under way reaches primary completion within a year.
Among the 114 studies testing lapatinib in Breast Neoplasms, from their registry updates:
Nothing recorded among them since 2026-09-25.
Among Baylor Breast Care Center’s 16 in Breast Neoplasms:
Nothing recorded among them since 2026-09-25.
We want to learn whether GW572016 is effective in breast cancers that have HER2.
The EGFR/HER family of transmembrane type I receptor tyrosine kinases are enzymes that play an important role in fundamental cell processes like cell proliferation, differentiation, and survival. These receptor tyrosine kinases, which include HER1 (epidermal growth factor receptor, EGFR), HER2 (HER2/neu, c-erbB2), HER3 and HER4 contain an extracellular domain and intracellular protein tyrosine kinase core. Aberrant HER1 and HER2 signaling has been causally associated with cancer cell proliferation and survival.
HER1 is expressed or over-expressed in many human solid tumors and plays an important role in progression to invasion and metastases.. The association between HER2 overexpression and poor prognosis in node-positive and advanced breast cancer has been shown by a number of studies. Based on this association between the members of HER1/HER2 family and worse clinical outcome, antibodies and small molecules that specifically target these receptor tyrosine kinases were developed for their therapeutic efficacy.
Trastuzumab (Herceptin) is a highly purified recombinant DNA-derived humanized monoclonal antibody that selectively binds with high affinity to the extracellular domain of the HER2 receptor. Pivotal multicenter efficacy trials in metastatic patients showed improved response rates and disease-free survival in patients who received trastuzumab in addition to chemotherapy. One of these studies was an open-labeled, multicenter, randomized phase III study evaluating the addition of trastuzumab to standard first-line chemotherapy in metastatic breast cancer. This study randomized 469 patients with metastatic disease to chemotherapy with or without trastuzumab. Results of this study showed survival in patients who received trastuzumab plus chemotherapy to be almost twice as long as chemotherapy alone (7.2 vs. 4.5 months, p\<0.0001).
As dimerization is important in signal transduction, therapies that target more than one member of the HER family may have greater anti-tumor effect. Recently, data with trastuzumab plus IMC-C224 in human ovarian cancer cells showed greater growth inhibition compared to either monoclonal antibody alone. GW572016 is an orally active dual HER1/HER2 kinase inhibitor that blocks signal transduction pathways. This dual inhibition is an attractive therapeutic strategy for epithelial cancers, as ligand-induced HER1/HER2 dimerization triggers off potent proliferative and survival signals. In vitro studies with GW572016 have shown marked activity, leading to growth arrest and apoptosis in HER1 and HER2 overexpressing cell lines. GW572016 markedly reduced tyrosine phosphorylation of HER1 and HER2, and activation of MAP kinase and Akt, the downstream effectors of proliferation and survival, respectively. In vitro studies in HER-2 overexpressing cell lines have demonstrated synergistic activity when GW572016 is combined with taxanes. Phase I studies with GW572016 and taxanes have been completed, with results demonstrating that this small molecule inhibitor may be safely combined with chemotherapy with no unanticipated side effects.
The EGFR/HER family of transmembrane type I receptor tyrosine kinases are enzymes that play an important role in fundamental cell processes like cell proliferation, differentiation, and survival. These receptor tyrosine kinases, which include HER1 (epidermal growth factor receptor, EGFR), HER2 (HER2/neu, c-erbB2), HER3 and HER4 contain an extracellular domain and intracellular protein tyrosine kinase core. Aberrant HER1 and HER2 signaling has been causally associated with cancer cell proliferation and survival.
Trastuzumab (Herceptin) is a highly purified recombinant DNA-derived humanized monoclonal antibody that selectively binds with high affinity to the extracellular domain of the HER2 receptor. Results of this study showed survival in patients who received trastuzumab plus chemotherapy to be almost twice as long as chemotherapy alone (7.2 vs. 4.5 months, p\<0.0001).
In vitro studies with GW572016 have shown marked activity, leading to growth arrest and apoptosis in HER1 and HER2 overexpressing cell lines. GW572016 markedly reduced tyrosine phosphorylation of HER1 and HER2, and activation of MAP kinase and Akt, the downstream effectors of proliferation and survival, respectively. In vitro studies in HER-2 overexpressing cell lines have demonstrated synergistic activity when GW572016 is combined with taxanes. Phase I studies with GW572016 and taxanes have been completed, with results demonstrating that this small molecule inhibitor may be safely combined with chemotherapy with no unanticipated side effects.
As the type I tyrosine kinases are involved in various aspects of cell growth and survival, a potent quinazoline and pyrido-[3,4-d]-pyrimidine small molecule (GW572016) against HER1 and HER2 was developed which showed potent in vitro inhibition of HER1 and HER2 in tumor cell lines. Mouse xenograft models of BT474 and HN5 cell lines also showed growth inhibition in a dose-responsive manner. In addition, GW572016 caused a reduction in HER1 and HER2 autophosphorylation, indicating interference of this signaling pathway. GW572016 not only inhibited baseline activation of HER1 and HER2, but also has been shown to interrupt downstream activation of Erk1/2 MAP kinases and Akt.
HER1 is expressed or over-expressed in many human solid tumors and plays an important role in progression to invasion and metastases.. The association between HER2 overexpression and poor prognosis in node-positive and advanced breast cancer has been shown by a number of studies. Based on this association between the members of HER1/HER2 family and worse clinical outcome, antibodies and small molecules that specifically target these receptor tyrosine kinases were developed for their therapeutic efficacy.
Trastuzumab (Herceptin) is a highly purified recombinant DNA-derived humanized monoclonal antibody that selectively binds with high affinity to the extracellular domain of the HER2 receptor. Pivotal multicenter efficacy trials in metastatic patients showed improved response rates and disease-free survival in patients who received trastuzumab in addition to chemotherapy. One of these studies was an open-labeled, multicenter, randomized phase III study evaluating the addition of trastuzumab to standard first-line chemotherapy in metastatic breast cancer. This study randomized 469 patients with metastatic disease to chemotherapy with or without trastuzumab. Results of this study showed survival in patients who received trastuzumab plus chemotherapy to be almost twice as long as chemotherapy alone (7.2 vs. 4.5 months, p\<0.0001).
We have completed the first single-agent neoadjuvant trastuzumab study in human breast cancer. The specific aims of this study were to firstly, define the clinical efficacy of trastuzumab, and secondly, to determine its mechanism of action in human breast cancer specimens. From September 1999 to June 2003, 27 patients with HER2 overexpressing locally advanced breast cancer with or without gross metastatic disease, were considered for a phase II study with neoadjuvant trastuzumab. At presentation, the median tumor size was large at 8x8 cm2 (range 4x4 cm2 to 25x20 cm2). We did not expect measurable evidence of tumor regression with this short treatment duration. However, regression in the product of bidimensional tumor measurements with a median decrease of -20.0% (range 0, -60.4%, p=0.0001) was observed in primary tumors after only 3 weeks of single agent trastuzumab. Most surprisingly, partial response was observed in 26% (7/27). Minor response was seen in 44% (12/27), and stable disease in 30% (8/27). No tumors increased in size during this 3-week period.
This is the first neoadjuvant trastuzumab monotherapy study in treatment-naive patients with HER2 overexpressing breast cancers. The clinical efficacy with tumor reductions in some patients presenting with large initial tumors indicates that the monoclonal antibody can be safely administered as a single agent without fear of tumor progression. When the study was first started, the uncertainty of the clinical efficacy of neoadjuvant single agent trastuzumab limited its duration to 3 weeks. It seems likely that the true response rate would have been higher if therapy was continued for several months. Based on these data, longer treatment durations of HER2 targeted therapy, like with GW572016, given as a single agent should be investigated in clinical trials with careful monitoring of patients to assess its activity in this setting.
Aim 1: To demonstrate the clinical efficacy of GW572016 when given as neoadjuvant therapy as a single agent in patients with treatment-naive, locally advanced HER2 overexpressing breast cancer. We aim to discover the true response rate to inhibiting HER1/2 signal transduction with GW572016 in breast cancer patients.
Aim 2: To determine if GW572016 inhibits HER1 and HER2 signaling in situ.The mechanism of therapeutic action of GW572016 is not fully understood.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
HER2 is a protein, made from the ERBB2 gene, that drives the growth of some cancers. A study may look for a level of the protein, extra copies of the gene, or a particular change in it.
In breast cancer, protein tests are read as HER2-positive, HER2-low or HER2-negative; other cancers use their own rules. Check which test result the study requires.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Cancer that has spread to the leptomeninges, the thin layers covering the brain and spinal cord, and the fluid between them. It is not the same as brain metastases.
Criteria often treat it separately, and many studies leave it out even where treated brain metastases are allowed.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HER2
HER2 is a protein, made from the ERBB2 gene, that drives the growth of some cancers. A study may look for a level of the protein, extra copies of the gene, or a particular change in it.
In breast cancer, protein tests are read as HER2-positive, HER2-low or HER2-negative; other cancers use their own rules. Check which test result the study requires.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Life expectancy
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Leptomeningeal disease
Cancer that has spread to the leptomeninges, the thin layers covering the brain and spinal cord, and the fluid between them. It is not the same as brain metastases.
Criteria often treat it separately, and many studies leave it out even where treated brain metastases are allowed.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
LVEF (left ventricular ejection fraction)
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Intervention/Lapatinib (GW572016)
Drug: GW572016 · Drug: lapatinib
Clinical Response
Clinical efficacy was assessed by bidimensional tumor measurements of the primary cancer at baseline, and at the end of week 6. Clinical complete response (cCR) was defined as complete disappearance of the primary tumor. Clinical partial response (cPR) was defined as a decrease by at least 50% of the sum of the products of the largest perpendicular diameters. An increase of more than 25% was defined as clinical progressive disease (cPD). Any response that does not meet the definition of cCR, cPR, or cPD was defined as stable disease (cSD).
Time frame: at the end of week 6.
Inhibition of HER1 and HER2 Signaling as Determined by EGFR, HER2, and pHER2
Immunohistochemical staining of cells from patients breast biopsies at baseline and post-treatment (week 6) were performed. Biologic markers including EGFR, HER2, and pHER2 were assessed with intensity scores of the staining (0-3, higher score means higher intensity).
Time frame: Baseline and 6 weeks
Inhibition of HER1 and HER2 Signaling as Determined by ki67 and CC3
Immunohistochemical staining of cells from patients breast biopsies at baseline and post-treatment (week 6) were performed. Biologic markers of Ki67 and CC3 were assessed with percentages of cells staining positive (0%-100%, higher score means higher positive cells).
Time frame: Baseline and 6 weeks
| Milestone | GW572016 1500mg |
|---|---|
| Started | 49 |
| Completed | 47 |
| Not completed | 2 |
| Withdrew: Adverse event | 2 |
Clinical efficacy was assessed by bidimensional tumor measurements of the primary cancer at baseline, and at the end of week 6. Clinical complete response (cCR) was defined as complete disappearance of the primary tumor. Clinical partial response (cPR) was defined as a decrease by at least 50% of the sum of the products of the largest perpendicular diameters. An increase of more than 25% was defined as clinical progressive disease (cPD). Any response that does not meet the definition of cCR, cPR, or cPD was defined as stable disease (cSD).
| participants | GW572016 1500mg |
|---|---|
| cCR | 3 |
| cPR | 30 |
| cSD | 11 |
| cPD | 3 |
Immunohistochemical staining of cells from patients breast biopsies at baseline and post-treatment (week 6) were performed. Biologic markers including EGFR, HER2, and pHER2 were assessed with intensity scores of the staining (0-3, higher score means higher intensity).
| score on a scale | GW572016 1500mg |
|---|---|
| EGFR at baseline | 0 (0 to 1) |
| EGFR at week 6 | 0 (0 to 1) |
| HER2 at baseline | 3 (2.75 to 3) |
| HER2 at week 6 | 3 (2.5 to 3) |
| pHER2 at baseline | 1.5 (0 to 2.5) |
| pHER2 at week 6 | 1.5 (0 to 2.5) |
Immunohistochemical staining of cells from patients breast biopsies at baseline and post-treatment (week 6) were performed. Biologic markers of Ki67 and CC3 were assessed with percentages of cells staining positive (0%-100%, higher score means higher positive cells).
| percentage of cells staining positive | GW572016 1500mg |
|---|---|
| Ki67 at baseline | 71 (54 to 78) |
| Ki67 at week 6 | 49 (29 to 65) |
| CC3 at baseline | 1.80 (0.82 to 3.11) |
| CC3 at week 6 | 1.84 (0.50 to 5.31) |
Collected over During the 6-week therapy. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| GW572016 1500mg | — | 3/49 (6.1%) | 32/49 (65.3%) |
| Event | GW572016 1500mg |
|---|---|
| rashSkin and subcutaneous tissue disorders | 1/49 |
| Neutrophils/ANCBlood and lymphatic system disorders | 1/49 |
| LeukocytesBlood and lymphatic system disorders | 1/49 |
| HypocalcemiaBlood and lymphatic system disorders | 1/49 |
| ConstipationGastrointestinal disorders | 1/49 |
| Febrile neutropeniaBlood and lymphatic system disorders | 1/49 |
| Infection-oral thrushInfections and infestations | 1/49 |
| Mucositis-oralGastrointestinal disorders | 1/49 |
| Left Ventricular Systolic DysfunctionCardiac disorders | 1/49 |
| Event | GW572016 1500mg |
|---|---|
| DiarrheaGastrointestinal disorders | 23/49 |
| RashSkin and subcutaneous tissue disorders | 18/49 |
| Elevated ASTHepatobiliary disorders | 4/49 |
| NauseaGastrointestinal disorders | 4/49 |
| BruisingSkin and subcutaneous tissue disorders | 3/49 |
| PruritisSkin and subcutaneous tissue disorders | 3/49 |
| Age, Continuous(years) | GW572016 1500mg |
|---|---|
| Median | 53 (27 to 83) |
| Sex: Female, Male(Participants) | GW572016 1500mg |
|---|---|
| Female | 49 |
| Male | 0 |
This study is completed, as verified in Sep 2021. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Lapatinib
Baylor Breast Care Center