Breast CancerPhase 1/2PGSNCT01070706
Phase Ib/II Study of Primary Chemotherapy With Paclitaxel, Gemcitabine, and Sunitinib
A Phase 1/2 study testing Paclitaxel,Gemcitabine,Sunitinib in people with Breast Cancer, run by Jungsil Ro at 1 site in South Korea.
Trial summary
Phase Ib part: ▪ Primary objective: To demonstrate the recommended dose of the combination of paclitaxel, gemcitabine, and sunitinib (sutene®) (PGS) as preoperative chemotherapy in patients with HER2-negative operable breast cancer Secondary objective: 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,Sunitinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteSouth Korea
- Study dates
- Mar 2009to Nov 2010
- Phase
- Phase 1/2
- 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
- Age ≥ 18 years
- ECOG performance status 0-2
- Histologically confirmed and newly diagnosed breast cancer
- Documented HER2/neu non-overexpressing or non-amplified disease
- 0-1+ by HER2 IHC or
- HER2 gene non-amplification by HER2 FISH
Show all 21Show fewer
- Clinical stage II or III operable breast cancer
- Axillary node positivity determined by cytology
- No prior hormonal, chemotherapy or radiotherapy is allowed
- No breast operation other than biopsy to make diagnosis is allowed
- Adequate hematologic, hepatic and renal function
- Absolute neutrophil count ≥ 1,500/μL
- Hemoglobin ≥ 10.0 g/dL
- Platelet ≥ 100,000/μL
- AST/ALT ≤ 2 X UNL (upper limit of normal)
- Total bilirubin ≤ 1.5 mg/dL
- Alkaline phosphatase ≤ 2 X UNL
- Serum creatinine ≤ 1.5 mg/dL
- Adequate cardiac function LVEF ≥ 50% and within the institutional range of normal as measured by echocardiogram or MUGA scan within 4 weeks of enrollment
- Women of childbearing potential must have a negative urine pregnancy test within 7 days prior to registration
- Normal mental function to understand and sign the consent
Who cannot join
- Patients with metastatic breast cancer
- Patients who received hormonal, chemotherapy or radiotherapy for breast cancer
- Patients who underwent surgery for breast cancer
- Patients with T2N0, or inflammatory (T4d) 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 inflammatory GI disease (e.g., Crohn's disease, ulcerative colitis)
Show all 19Show fewer
- Any of the following within the 12 months prior to starting study treatment
- severe, unstable angina
- Myocardial infarction
- Uncontrolled or symptomatic congestive heart failure
- coronary/peripheral artery bypass graft
- cerebrovascular accident including transient ischemic attack
- pulmonary embolism
- Ongoing cardiac dysrhythmias of grade ≥2, atrial fibrillation of any grade, or QTc interval >470 msec.
- Hypertension that cannot be controlled by medications (>150/100 mmHg despite optimal medical therapy)
- Current treatment with therapeutic doses of Coumadin (low dose Coumadin up to 2 mg po daily for deep vein thrombosis prophylaxis is allowed).
- Known HIV infection
- Pregnancy or breastfeeding. Female patients who are pregnant or nursing, female of child-bearing potential who is unwilling to use adequate contraception to prevent pregnancy during the program. All female patients with reproductive potential must have a negative pregnancy test (serum or urine) prior to study entry.
- Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that would impart, in the judgment of the investigator, excess risk associated with study participation or study drug during administration, or which, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
Trial locations and contacts
1 site in 1 country.
South Korea1 site
Center for breast cancer, National Cancer Center
Goyang, Kyeonggido, 410-769
About this study
Official title: Phase Ib/II Study of Primary Chemotherapy With Paclitaxel, Gemcitabine, and Sunitinib in Patients With HER2-negative Stage II/III Breast Cancer
Phase Ib part:
▪ Primary objective: To demonstrate the recommended dose of the combination of paclitaxel, gemcitabine, and sunitinib (sutene®) (PGS) as preoperative chemotherapy in patients with HER2-negative operable breast cancer
Read more
- Secondary objective:
- To demonstrate the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of this regimen
- To determine the safety profile Phase II part
- Primary objective:
To evaluate the pathologic complete response rate (pCR) to preoperative administration of PGS
▪ Secondary objective:
- To assess breast conserving rate after preoperative PGS
- To evaluate clinical response rate, disease free survival (DFS), and overall survival (OS)
- To assess the safety profiles of PGS
Read the detailed description
Unlike adjuvant chemotherapy, primary (preoperative) chemotherapy will shrink tumor and allow more 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 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 paclitaxel and gemcitabine (PG) resulted in improvement in objective response rate, time to progression and overall survival compared to paclitaxel monotherapy in patients with metastatic breast cancer. In addition, primary chemotherapies with PG and PGH (PG + trastuzumab) showed significant activity and very low toxicity in phase II studies performed at National Cancer Center, Korea (ASCO 2007 and SABCS 2008, respectively).
Sunitinib is an oral small molecular tyrosine kinase inhibitor that exhibits potent anti-angiogenic and antitumor activity. Sunitinib is a rationally designed small molecule that inhibits members of the split-kinase domain family of receptor tyrosine kinases (RTKs) including the vascular endothelial growth factors (VEGFs) types 1, 2, and 3, platelet-derived growth factor receptor (PDGFR)-α, and -β, stem cell factor receptor (KIT), colony stimulating factor 1 receptor (CSF-1R), Fms-like tyrosine kinase (FLT-3), and glial cell line-derived neurotrophic factor receptor (RET). Inhibition of these RTKs blocks signal transduction, thereby affecting many of the process involved in tumor growth, progression, metastasis, and angiogenesis. Angiogenesis plays a vital role in the growth and metastasis of solid tumors. Preclinical and indirect clinical evidence has accumulated to support the role of neo-angiogenesis in the pathogenesis and progression of breast cancer. Breast cancer neo-vascularization, as measured by an increase in microvessel density, is correlated with the extent of disease and is associated with vascular invasion of the tumor, a prerequisite for blood-borne metastasis. VEGFR signaling is also implicated in the pathobiology of breast cancer. Breast cancer patients exhibit high levels of circulating VEGF and other RTKs are very likely implicated in breast cancer pathogenesis.
Interestingly, a phase II study (Study A6181002) of single-agent sunitinib (50 mg/d on schedule 4/2) in breast cancer patients with anthracycline- and taxane-refractory metastatic disease revealed a response rate of approximately 14% in 51 assessable patients, leading to additional accrual.
When sunitinib is combined with paclitaxel, significant activity was noticed with tolerable toxicity profile in a phase I trial (SABCS 2007). Based on this trial, phase III trial of paclitaxel and sunitinib is ongoing. In addition, phase I trials of gemcitabine and sunitinib combination are ongoing.
Based both on the significant activity of PG combination regimens in the neoadjuvant and metastatic setting and on the phase I trials of combination regimens with sunitinib-paclitaxel and sunitinib-gemcitabine, we plan to conduct a phase IB/II study of primary chemotherapy with sunitinib, paclitaxel and gemcitabine in patients with HER2-negative stage II/III breast cancer. The goal of this phase IB/II study is to define the recommended dose and maximum tolerable dose of paclitaxel and gemcitabine in combination with sunitinib, and explore the activity of this combination as preoperative chemotherapy in patients with HER2-negative operable breast cancer.
- Conditions
- Breast Cancer
- Being tested
- Paclitaxel,Gemcitabine,Sunitinib
- Keywords
- Patients with HER2- stage II/III 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,SunitinibDrug
Also called PGS
To determine the MTD, only DLT occurring during the first cycle of treatment will be considered. And MTD is defined as the dose level at which at least one-third of patients experience a DLT during their first treatment course. The recommended dose level for the subsequent phase II study is defined as the preceding dose level before the MTD is attained.
If MTD is not reached, the recommended initial dose of the phase II part will be at the dose of paclitaxel 80 mg/m2 and gemcitabine 1200 mg/m2 (days 1, 8) with sunitinib 37.5 mg qd D2-D15.
| Study group | Role | What they receive |
|---|---|---|
| Paclitaxel, Gemcitabine, Sunitinib | Experimental | Paclitaxel, Gemcitabine, Sunitinib Receives: Drug: Paclitaxel,Gemcitabine,Sunitinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase Ib part: To demonstrate the recommended dose of the combination of paclitaxel, gemcitabine, and sunitinib. Phase II part: To evaluate the pathologic complete response rate (pCR)
Measured: 17Mar2009~08Apr2010
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Feb 2010 (estimated)
- Study startMar 2009
- Primary completionDec 2009
- Study completionNov 2010
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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jungsil Ro
- Sponsor type
- Other government
- Collaborators
- Pfizer, HK inno.N Corporation
- Responsible party
- Sponsor-investigator, Jungsil Ro, National Cancer Center, Korea
- Investigators
- Jungsil Ro, Principal investigator, Chief, Center for Breast Cancer, National Cancer Center, Korea
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01070706
- Sponsor's protocol ID
- NCCCTS-08-369
- Acronym
- PGS
- 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/II Study of Primary Chemotherapy With Paclitaxel, Gemcitabine, and Sunitinib in Patients With HER2-negative Stage II/III Breast Cancer
- ClinicalTrials.gov ID
- NCT01070706
- Acronym / sponsor ID
- PGS / NCCCTS-08-369
- Conditions
- Breast Cancer
- Keywords
- Patients with HER2- stage II/III breast cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Jungsil RoOther government
- Collaborators
- Pfizer, HK inno.N Corporation
- Study start
- Mar 2009
- Primary completion
- Dec 2009 (actual)
- Study completion
- Nov 2010 (actual)
- First posted
- 18 Feb 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.
Phase Ib part:
▪ Primary objective: To demonstrate the recommended dose of the combination of paclitaxel, gemcitabine, and sunitinib (sutene®) (PGS) as preoperative chemotherapy in patients with HER2-negative operable breast cancer
- Secondary objective:
- To demonstrate the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of this regimen
- To determine the safety profile Phase II part
- Primary objective:
To evaluate the pathologic complete response rate (pCR) to preoperative administration of PGS
▪ Secondary objective:
- To assess breast conserving rate after preoperative PGS
- To evaluate clinical response rate, disease free survival (DFS), and overall survival (OS)
- To assess the safety profiles of PGS
Detailed description
Unlike adjuvant chemotherapy, primary (preoperative) chemotherapy will shrink tumor and allow more 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 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 paclitaxel and gemcitabine (PG) resulted in improvement in objective response rate, time to progression and overall survival compared to paclitaxel monotherapy in patients with metastatic breast cancer. In addition, primary chemotherapies with PG and PGH (PG + trastuzumab) showed significant activity and very low toxicity in phase II studies performed at National Cancer Center, Korea (ASCO 2007 and SABCS 2008, respectively).
Sunitinib is an oral small molecular tyrosine kinase inhibitor that exhibits potent anti-angiogenic and antitumor activity. Sunitinib is a rationally designed small molecule that inhibits members of the split-kinase domain family of receptor tyrosine kinases (RTKs) including the vascular endothelial growth factors (VEGFs) types 1, 2, and 3, platelet-derived growth factor receptor (PDGFR)-α, and -β, stem cell factor receptor (KIT), colony stimulating factor 1 receptor (CSF-1R), Fms-like tyrosine kinase (FLT-3), and glial cell line-derived neurotrophic factor receptor (RET). Inhibition of these RTKs blocks signal transduction, thereby affecting many of the process involved in tumor growth, progression, metastasis, and angiogenesis. Angiogenesis plays a vital role in the growth and metastasis of solid tumors. Preclinical and indirect clinical evidence has accumulated to support the role of neo-angiogenesis in the pathogenesis and progression of breast cancer. Breast cancer neo-vascularization, as measured by an increase in microvessel density, is correlated with the extent of disease and is associated with vascular invasion of the tumor, a prerequisite for blood-borne metastasis. VEGFR signaling is also implicated in the pathobiology of breast cancer. Breast cancer patients exhibit high levels of circulating VEGF and other RTKs are very likely implicated in breast cancer pathogenesis.
Interestingly, a phase II study (Study A6181002) of single-agent sunitinib (50 mg/d on schedule 4/2) in breast cancer patients with anthracycline- and taxane-refractory metastatic disease revealed a response rate of approximately 14% in 51 assessable patients, leading to additional accrual.
When sunitinib is combined with paclitaxel, significant activity was noticed with tolerable toxicity profile in a phase I trial (SABCS 2007). Based on this trial, phase III trial of paclitaxel and sunitinib is ongoing. In addition, phase I trials of gemcitabine and sunitinib combination are ongoing.
Based both on the significant activity of PG combination regimens in the neoadjuvant and metastatic setting and on the phase I trials of combination regimens with sunitinib-paclitaxel and sunitinib-gemcitabine, we plan to conduct a phase IB/II study of primary chemotherapy with sunitinib, paclitaxel and gemcitabine in patients with HER2-negative stage II/III breast cancer. The goal of this phase IB/II study is to define the recommended dose and maximum tolerable dose of paclitaxel and gemcitabine in combination with sunitinib, and explore the activity of this combination as preoperative chemotherapy in patients with HER2-negative operable breast cancer.
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, Sunitinib | Experimental | Drug: Paclitaxel,Gemcitabine,SunitinibPaclitaxel, Gemcitabine, Sunitinib |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Age ≥ 18 years
- ECOG performance status 0-2
- Histologically confirmed and newly diagnosed breast cancer
- Documented HER2/neu non-overexpressing or non-amplified disease
- Clinical stage II or III operable breast cancer
Key exclusion criteria (19 listed)
- Patients with metastatic breast cancer
- Patients who received hormonal, chemotherapy or radiotherapy for breast cancer
- Patients who underwent surgery for breast cancer
- Patients with T2N0, or inflammatory (T4d) breast cancer
- Patients who have history of cancer other than in situ uterine cervix cancer or nonmelanotic skin 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,SunitinibAlso: PGSTo determine the MTD, only DLT occurring during the first cycle of treatment will be considered. And MTD is defined as the dose level at which at least one-third of patients experience a DLT during their first treatment course. The recommended dose level for the subsequent phase II study is defined as the preceding dose level before the MTD is attained. If MTD is not reached, the recommended initial dose of the phase II part will be at the dose of paclitaxel 80 mg/m2 and gemcitabine 1200 mg/m2 (days 1, 8) with sunitinib 37.5 mg qd D2-D15. | Drug | Paclitaxel, Gemcitabine, Sunitinib |
Primary outcome
Phase Ib part: To demonstrate the recommended dose of the combination of paclitaxel, gemcitabine, and sunitinib. Phase II part: To evaluate the pathologic complete response rate (pCR)
Time frame: 17Mar2009~08Apr2010
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.
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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.
Jungsil Ro principal investigator
Chief, Center for Breast Cancer, National Cancer 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 1/2 study testing Paclitaxel,Gemcitabine,Sunitinib 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 21 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: 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 combined 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.
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?
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?
Phase Ib part: To demonstrate the recommended dose of the combination of paclitaxel, gemcitabine, and sunitinib. Phase II part: To evaluate the pathologic complete response rate (pCR) (time frame: 17Mar2009~08Apr2010). 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.