Breast CancerPhase 1PGTNCT01133912
Preoperative Chemotherapy With Paclitaxel, Gemcitabine, and Lapatinib (Tykerb®) (PGT)
A Phase 1 study testing paclitaxel, gemcitabine, lapatinib in people with Breast Cancer, run by Jungsil Ro at 1 site in South Korea.
Trial summary
Primary objectives : 1. To evaluate the recommended dose of the combination of paclitaxel, gemcitabine, and lapatinib (Tykerb®) (PGT) as preoperative chemotherapy in patients with HER2 positive operable breast cancer Secondary objectives : 1. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- paclitaxel, gemcitabine, lapatinib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteSouth Korea
- Study dates
- Mar 2009to Oct 2011
- 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
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed and newly diagnosed operable breast cancer
- Documented HER2 positive disease : 3+ overexpression by IHC or HER2 gene amplification by FISH
- ECOG performance status 0-2
- Age ≥ 18 years
- Clinical stage II or III operable breast cancer
- Axillary node positivity determined by cytology
Show all 17Show fewer
- No prior hormonal, chemotherapy, or radiotherapy is allowed
- No breast operation other than biopsy to make diagnosis is allowed
- Negative urine pregnancy test within 7 days prior to registration in premenopausal patients
- Adequate hematopoietic function: Absolute granulocyte count ≥1,500/mm3, platelet ≥100,000/mm3, hemoglobin ≥10g/mm3
- Adequate hepatic function: total bilirubin ≤1.5mg/dL, AST/ALT ≤2 x UNL, alkaline phosphatase ≤2 x UNL
- Adequate renal function: Serum creatinine ≤1.5mg/dL
- Adequate cardiac function:
- Normal or nonspecific EKG taken within 1 month of enrollment
- LVEF ≥50% by MUGA or echocardiogram taken within 4 weeks of enrollment
- Ability to understand and comply with protocol during study period
- Patients should sign a written informed consent before study entry
Who cannot join
- Pregnant or lactating women
- Patients who received hormonal, chemotherapy or radiotherapy for breast cancer
- Patients with bilateral breast cancer
- Patients who underwent surgery for breast cancer
- Patients with node-negative stage IIA (T2N0) breast cancer
- Patients who have history of cancer other than in situ uterine cervix cancer or nonmelanotic skin cancer
- Patients with GI tract disease resulting in an inability to take oral medication, malabsorption syndrome, a requirement for IV alimentation, prior surgical procedures affecting absorption, uncontrolled GI disease (e.g., Crohn's disease, ulcerative colitis)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase Ib Study of Preoperative Chemotherapy With Paclitaxel, Gemcitabine, and Lapatinib (Tykerb®) (PGT) in Patients With HER2 Positive Operable Breast Cancer
Primary objectives :
- To evaluate the recommended dose of the combination of paclitaxel, gemcitabine, and lapatinib (Tykerb®) (PGT) as preoperative chemotherapy in patients with HER2 positive operable breast cancer
Secondary objectives :
- To evaluate the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of PGT
- To determine the safety profile
- To assess pCR in primary tumor and axillary LN
- To evaluate clinical response rate, disease free survival (DFS), and overall survival (OS)
- To assess breast conserving rate after preoperative PGT
Read the detailed description
Unlike adjuvant chemotherapy, primary (preoperative) chemotherapy will shrink tumor and allow some patients to become candidates for conservative surgery and avoid mastectomy. It also is an in vivo chemosensitivity test and the result is a predictive marker for clinical outcomes. Paclitaxel is a highly active antitumor agent that promotes microtubule assembly by binding to tubulin and inhibiting depolymerization. Paclitaxel has been shown to be an effective agent in the treatment of breast cancer. Gemcitabine is a cytosine arabinoside prodrug analog and shows response rates of 15% to 46% as a single agent with very low toxicity. The combination of gemcitabine and paclitaxel is valuable because of the different mechanisms of action of each drug and their non-overlapping toxicities. Phase II studies of paclitaxel plus gemcitabine in anthracycline-pretreated metastatic breast cancer showed good tolerance and encouraging response rates (40%-55%). Paclitaxel plus gemcitabine combination showed overall survival benefit compared to paclitaxel alone in patients with metastatic breast cancer in an interim overall survival report. A phase II study with preoperative paclitaxel and gemcitabine in stage II/III showed 18 % pCR rate at NCC (ASCO 2007 abstract #11080) In HER2 positive breast cancer, HER2 targeted therapies with trastuzumab and lapatinib have shown much improved clinical response in palliative setting. It also showed that adding trastuzumab to sequential paclitaxel and FEC chemotherapy significantly increased pCR (25% vs 66.7%) in preoperative setting for HER2 positive disease. Recently, paclitaxel, gemcitabine, and trastuzumab combination (PGH) for 6 cycles in patients with HER2 positive and node positive operable breast cancer observed a strikingly high pCR rate in both tumor and LN in an interim analysis of multicenter phase II preoperative study in Korea (28 of 47 (61%)). Lapatinib (Tykerb®), a dual tyrosine kinase inhibitor of ErbB1 and HER2 signaling pathways and it has shown to inhibit the growth of HER2 overexpressing breast cancer cells that do not respond to trastuzumab after long-term conditioning. We will examine the hypothesis that paclitaxel, gemcitabine, and lapatinib (Tykerb®) (PGT) combination could improve the pathological complete response rate of HER2 positive breast cancer when applied as a preoperative chemotherapy.
- Conditions
- Breast Cancer
- Being tested
- paclitaxel, gemcitabine, lapatinib
- Keywords
- Patients with HER2 Positive Operable Breast Cancer
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
paclitaxel, gemcitabine, lapatinibDrug
Also called Paclitaxel, Gemzar, Tykerb
Patients receive paclitaxel and gemcitabine intravenously (iv) on day 1 and 8, and oral lapatinib once daily. Lapatinib with fixed dose will be given once a day p.o. from day 1 without resting during each cycle. The starting doses of paclitaxel 80mg/m2 and gemcitabine 1000mg/m2 iv, on day 1 and 8, and lapatinib 1000mg p.o., daily (dose level 1) will be administered every 21 days.
| Study group | Role | What they receive |
|---|---|---|
| paclitaxel, gemcitabine, lapatinib | Experimental | paclitaxel 80mg/m2 D1, D8 gemcitabine 1000mg/m2 D1, D8, every 3 weeks, 6 cycle lapatinib(Tykerb®)1000mg every day Receives: Drug: paclitaxel, gemcitabine, lapatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate the recommended dose of the combination of paclitaxel, gemcitabine, and lapatinib (Tykerb®) (PGT) as preoperative chemotherapy in patients with HER2 positive operable breast cancer
Measured: two years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 May 2010 (estimated)
- Study startMar 2009
- Primary completionJun 2010
- Study completionOct 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast CancerStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jungsil Ro
- Sponsor type
- Other government
- Collaborators
- GlaxoSmithKline, HK inno.N Corporation
- Responsible party
- Sponsor-investigator, Jungsil Ro, National Cancer Center, Korea
- Investigators
- Jungsil Ro, MD, Principal investigator, National Cencer Center, Korea
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01133912
- Sponsor's protocol ID
- NCCCTS-08-370
- Acronym
- PGT
- Status last verified
- Jan 2012
- First submitted
- 17 Feb 2010
- Last updated
- 4 Jan 2012
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Jan 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase Ib Study of Preoperative Chemotherapy With Paclitaxel, Gemcitabine, and Lapatinib (Tykerb®) (PGT) in Patients With HER2 Positive Operable Breast Cancer
- ClinicalTrials.gov ID
- NCT01133912
- Acronym / sponsor ID
- PGT / NCCCTS-08-370
- Conditions
- Breast Cancer
- Keywords
- Patients with HER2 Positive Operable Breast Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Jungsil RoOther government
- Collaborators
- GlaxoSmithKline, HK inno.N Corporation
- Study start
- Mar 2009
- Primary completion
- Jun 2010 (actual)
- Study completion
- Oct 2011 (actual)
- First posted
- 31 May 2010 (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.
Primary objectives :
- To evaluate the recommended dose of the combination of paclitaxel, gemcitabine, and lapatinib (Tykerb®) (PGT) as preoperative chemotherapy in patients with HER2 positive operable breast cancer
Secondary objectives :
- To evaluate the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of PGT
- To determine the safety profile
- To assess pCR in primary tumor and axillary LN
- To evaluate clinical response rate, disease free survival (DFS), and overall survival (OS)
- To assess breast conserving rate after preoperative PGT
Detailed description
Unlike adjuvant chemotherapy, primary (preoperative) chemotherapy will shrink tumor and allow some patients to become candidates for conservative surgery and avoid mastectomy. It also is an in vivo chemosensitivity test and the result is a predictive marker for clinical outcomes. Paclitaxel is a highly active antitumor agent that promotes microtubule assembly by binding to tubulin and inhibiting depolymerization. Paclitaxel has been shown to be an effective agent in the treatment of breast cancer. Gemcitabine is a cytosine arabinoside prodrug analog and shows response rates of 15% to 46% as a single agent with very low toxicity. The combination of gemcitabine and paclitaxel is valuable because of the different mechanisms of action of each drug and their non-overlapping toxicities. Phase II studies of paclitaxel plus gemcitabine in anthracycline-pretreated metastatic breast cancer showed good tolerance and encouraging response rates (40%-55%). Paclitaxel plus gemcitabine combination showed overall survival benefit compared to paclitaxel alone in patients with metastatic breast cancer in an interim overall survival report. A phase II study with preoperative paclitaxel and gemcitabine in stage II/III showed 18 % pCR rate at NCC (ASCO 2007 abstract #11080) In HER2 positive breast cancer, HER2 targeted therapies with trastuzumab and lapatinib have shown much improved clinical response in palliative setting. It also showed that adding trastuzumab to sequential paclitaxel and FEC chemotherapy significantly increased pCR (25% vs 66.7%) in preoperative setting for HER2 positive disease. Recently, paclitaxel, gemcitabine, and trastuzumab combination (PGH) for 6 cycles in patients with HER2 positive and node positive operable breast cancer observed a strikingly high pCR rate in both tumor and LN in an interim analysis of multicenter phase II preoperative study in Korea (28 of 47 (61%)). Lapatinib (Tykerb®), a dual tyrosine kinase inhibitor of ErbB1 and HER2 signaling pathways and it has shown to inhibit the growth of HER2 overexpressing breast cancer cells that do not respond to trastuzumab after long-term conditioning. We will examine the hypothesis that paclitaxel, gemcitabine, and lapatinib (Tykerb®) (PGT) combination could improve the pathological complete response rate of HER2 positive breast cancer when applied as a preoperative chemotherapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| paclitaxel, gemcitabine, lapatinib | Experimental | Drug: paclitaxel, gemcitabine, lapatinibpaclitaxel 80mg/m2 D1, D8 gemcitabine 1000mg/m2 D1, D8, every 3 weeks, 6 cycle lapatinib(Tykerb®)1000mg every day |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Histologically confirmed and newly diagnosed operable breast cancer
- Documented HER2 positive disease : 3+ overexpression by IHC or HER2 gene amplification by FISH
- ECOG performance status 0-2
- Age ≥ 18 years
- Clinical stage II or III operable breast cancer
Key exclusion criteria (7 listed)
- Pregnant or lactating women
- Patients who received hormonal, chemotherapy or radiotherapy for breast cancer
- Patients with bilateral breast cancer
- Patients who underwent surgery for breast cancer
- Patients with node-negative stage IIA (T2N0) breast cancer
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 |
|---|---|---|
| paclitaxel, gemcitabine, lapatinibAlso: Paclitaxel, Gemzar, TykerbPatients receive paclitaxel and gemcitabine intravenously (iv) on day 1 and 8, and oral lapatinib once daily. Lapatinib with fixed dose will be given once a day p.o. from day 1 without resting during each cycle. The starting doses of paclitaxel 80mg/m2 and gemcitabine 1000mg/m2 iv, on day 1 and 8, and lapatinib 1000mg p.o., daily (dose level 1) will be administered every 21 days. | Drug | paclitaxel, gemcitabine, lapatinib |
Primary outcome
To evaluate the recommended dose of the combination of paclitaxel, gemcitabine, and lapatinib (Tykerb®) (PGT) as preoperative chemotherapy in patients with HER2 positive operable breast cancer
Time frame: two years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jan 2012.
Related trials for Breast Cancer
Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
RecruitingPhase 2
Gene Signatures to Guide HR+MBC Therapy in a Diverse Cohort
Invasive Mammary Carcinoma, Metastatic Breast Cancer
Not yet recruitingObservational study
Comparison of Reliability, Time Cost, and Participant Comfort of Lymphedema Assessments in Upper Extremity
Lymphedema, Upper Extremity Lymphedema
RecruitingPhase 3
A Study of Camrelizumab Plus Chemotherapy in Combination With or Without Famitinib as Neoadjuvant Therapy in Participants With Triple Negative Breast Cancer (BCTOP-T-N01)
TNBC - Triple-Negative Breast Cancer
RecruitingPhase 3
Testing Whether Hormone Therapy With Ribociclib is as Effective as Chemotherapy Followed by Hormone Therapy With Ribociclib for the Treatment of High Anatomic Stage Breast Cancer With Low Recurrence Risk, The RxFINE-Low Trial
Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8
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.
Jungsil Ro, MD principal investigator
National Cencer Center, Korea
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 paclitaxel, gemcitabine, lapatinib in people with Breast Cancer, run by Jungsil Ro at 1 site in South Korea.
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 17 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: finished, as of the sponsor's last update on 4 Jan 2012. 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 South Korea. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To evaluate the recommended dose of the combination of paclitaxel, gemcitabine, and lapatinib (Tykerb®) (PGT) as preoperative chemotherapy in patients with HER2 positive operable breast cancer (time frame: two years). 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 4 Jan 2012.