Phase Ib/II Study of Primary Chemotherapy With Paclitaxel, Gemcitabine, and Sunitinib

NCT01070706

Last updated date
Study Location
Center for breast cancer, National Cancer Center
Goyang, Kyeonggido, 410-769, Korea, Republic of
Contact
1-800-718-1021

FOR MORE INFORMATION

Contact a representative by phone, email, or visiting the study website. Please see the references below:

By phone

Pfizer Clinical Trials Contact Center

1-800-718-1021

By email

Contact

[email protected]

Call Now

Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Breast Cancer
Sex
Female
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
18 + years
Inclusion Criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

1. Age ≥ 18 years

2. ECOG performance status 0-2

3. Histologically confirmed and newly diagnosed breast cancer

4. Documented HER2/neu non-overexpressing or non-amplified disease

- 0-1+ by HER2 IHC or

- HER2 gene non-amplification by HER2 FISH

5. Clinical stage II or III operable breast cancer

6. Axillary node positivity determined by cytology

7. No prior hormonal, chemotherapy or radiotherapy is allowed

8. No breast operation other than biopsy to make diagnosis is allowed

9. 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

10. Adequate cardiac function LVEF ≥ 50% and within the institutional range of normal as measured by echocardiogram or MUGA scan within 4 weeks of enrollment

11. Women of childbearing potential must have a negative urine pregnancy test within 7 days prior to registration

12. Normal mental function to understand and sign the consent

Exclusion Criteria
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details


1. Patients with metastatic breast cancer


2. Patients who received hormonal, chemotherapy or radiotherapy for breast cancer


3. Patients who underwent surgery for breast cancer


4. Patients with T2N0, or inflammatory (T4d) breast cancer


5. Patients who have history of cancer other than in situ uterine cervix cancer or
nonmelanotic skin cancer


6. 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)


7. 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


8. Ongoing cardiac dysrhythmias of grade ≥2, atrial fibrillation of any grade, or QTc
interval >470 msec.


9. Hypertension that cannot be controlled by medications (>150/100 mmHg despite optimal
medical therapy)


10. Current treatment with therapeutic doses of Coumadin (low dose Coumadin up to 2 mg po
daily for deep vein thrombosis prophylaxis is allowed).


11. Known HIV infection


12. 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.


13. 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.

NEED INFO?

Questions about a trial? Call or email to reach a Pfizer Clinical Trial Contact Center Representative

Pfizer Clinical Trials Contact Center

1-800-718-1021

[email protected]

TRY A NEW SEARCH

Search for Clinical Trials by condition, keyword or trial number. Share your location or enter your city or zip code to find studies near you.

Based on your search, you may also be interested in

Breast CancerNeoadjuvant Letrozole and Palbociclib in Patients With Stage II-IIIB Breast Cancer, HR+, HER2 -
NCT03819010
  1. Badalona, Barcelona
  2. Madrid,
  3. Valencia,
  4. Oporto,
Female
18 Years+
years
MULTIPLE SITES
Breast CancerPALbociclib CoLlaborative Adjuvant Study
NCT02513394
  1. Mobile, Alabama
  2. Mobile, Alabama
  3. Anchorage, Alaska
  4. Anchorage, Alaska
  5. Phoenix, Arizona
  6. Greenbrae, California
  7. Greenbrae, California
  8. La Jolla, California
  9. Los Angeles, California
  10. Oakland, California
  11. Palo Alto, California
  12. Roseville, California
  13. Sacramento, California
  14. San Diego, California
  15. San Diego, California
  16. San Diego, California
  17. San Francisco, California
  18. San Francisco, California
  19. San Leandro, California
  20. Santa Clara, California
  21. South San Francisco, California
  22. Stanford, California
  23. Vallejo, California
  24. Walnut Creek, California
  25. Denver, Colorado
  26. Hartford, Connecticut
  27. New Britain, Connecticut
  28. Newark, Delaware
  29. Washington, District of Columbia
  30. Washington, District of Columbia
  31. Clearwater, Florida
  32. Jacksonville, Florida
  33. Miami Beach, Florida
  34. Miami, Florida
  35. Orlando, Florida
  36. Atlanta, Georgia
  37. Chicago, Illinois
  38. Chicago, Illinois
  39. Chicago, Illinois
  40. Decatur, Illinois
  41. Harvey, Illinois
  42. Joliet, Illinois
  43. Park Ridge, Illinois
  44. Peoria, Illinois
  45. Rockford, Illinois
  46. Skokie, Illinois
  47. Skokie, Illinois
  48. Urbana, Illinois
  49. Indianapolis, Indiana
  50. Muncie, Indiana
  51. Ames, Iowa
  52. Ames, Iowa
  53. Cedar Rapids, Iowa
  54. Des Moines, Iowa
  55. Waterloo, Iowa
  56. Lexington, Kentucky
  57. Louisville, Kentucky
  58. New Orleans, Louisiana
  59. Bangor, Maine
  60. Scarborough, Maine
  61. Annapolis, Maryland
  62. Baltimore, Maryland
  63. Baltimore, Maryland
  64. Baltimore, Maryland
  65. Baltimore, Maryland
  66. Baltimore, Maryland
  67. Baltimore, Maryland
  68. Bethesda, Maryland
  69. Salisbury, Maryland
  70. Silver Spring, Maryland
  71. Boston, Massachusetts
  72. Boston, Massachusetts
  73. Boston, Massachusetts
  74. Boston, Massachusetts
  75. Lowell, Massachusetts
  76. Plymouth, Massachusetts
  77. Ann Arbor, Michigan
  78. Grand Rapids, Michigan
  79. Livonia, Michigan
  80. Duluth, Minnesota
  81. Rochester, Minnesota
  82. Rochester, Minnesota
  83. Saint Cloud, Minnesota
  84. Saint Louis Park, Minnesota
  85. Saint Louis Park, Minnesota
  86. Kansas City, Missouri
  87. Rolla, Missouri
  88. Saint Louis, Missouri
  89. Saint Louis, Missouri
  90. Saint Louis, Missouri
  91. Springfield, Missouri
  92. Omaha, Nebraska
  93. Concord, New Hampshire
  94. Hooksett, New Hampshire
  95. Lebanon, New Hampshire
  96. Lebanon, New Hampshire
  97. Englewood, New Jersey
  98. Hackensack, New Jersey
  99. Albuquerque, New Mexico
  100. Albuquerque, New Mexico
  101. Bronx, New York
  102. Buffalo, New York
  103. East Syracuse, New York
  104. Jamaica, New York
  105. New Hyde Park, New York
  106. New York, New York
  107. New York, New York
  108. New York, New York
  109. Oneonta, New York
  110. Syracuse, New York
  111. Charlotte, North Carolina
  112. Durham, North Carolina
  113. Greensboro, North Carolina
  114. Pinehurst, North Carolina
  115. Rapid City, North Dakota
  116. Cleveland, Ohio
  117. Cleveland, Ohio
  118. Columbus, Ohio
  119. Mayfield Heights, Ohio
  120. Lawton, Oklahoma
  121. Oklahoma City, Oklahoma
  122. Oklahoma City, Oklahoma
  123. Portland, Oregon
  124. Dunmore, Pennsylvania
  125. Hershey, Pennsylvania
  126. Lancaster, Pennsylvania
  127. Philadelphia, Pennsylvania
  128. Philadelphia, Pennsylvania
  129. Philadelphia, Pennsylvania
  130. Philadelphia, Pennsylvania
  131. Pittsburgh, Pennsylvania
  132. Pittsburgh, Pennsylvania
  133. Wyomissing, Pennsylvania
  134. York, Pennsylvania
  135. Providence, Rhode Island
  136. Providence, Rhode Island
  137. Columbia, South Carolina
  138. Aberdeen, South Dakota
  139. Rapid City, South Dakota
  140. Sioux Falls, South Dakota
  141. Nashville, Tennessee
  142. Nashville, Tennessee
  143. Houston, Texas
  144. Houston, Texas
  145. Houston, Texas
  146. Laredo, Texas
  147. Salt Lake City, Utah
  148. Fairfax, Virginia
  149. Richmond, Virginia
  150. Charleston, West Virginia
  151. Appleton, Wisconsin
  152. Green Bay, Wisconsin
  153. La Crosse, Wisconsin
  154. Madison, Wisconsin
  155. Milwaukee, Wisconsin
  156. Milwaukee, Wisconsin
  157. Racine, Wisconsin
  158. Waukesha, Wisconsin
  159. Waukesha, Wisconsin
ALL GENDERS
18 Years+
years
MULTIPLE SITES
Advanced Information
Descriptive Information
Brief Title  ICMJE Phase Ib/II Study of Primary Chemotherapy With Paclitaxel, Gemcitabine, and Sunitinib
Official Title  ICMJE Phase Ib/II Study of Primary Chemotherapy With Paclitaxel, Gemcitabine, and Sunitinib in Patients With HER2-negative Stage II/III Breast Cancer
Brief 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. To demonstrate the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of this regimen
    2. 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:

  1. To assess breast conserving rate after preoperative PGS
  2. To evaluate clinical response rate, disease free survival (DFS), and overall survival (OS)
  3. 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)-?, and -?, 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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Breast Cancer
Intervention  ICMJE Drug: Paclitaxel,Gemcitabine,Sunitinib

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.

Other Name: PGS
Study Arms  ICMJE Experimental: Paclitaxel, Gemcitabine, Sunitinib
Paclitaxel, Gemcitabine, Sunitinib
Intervention: Drug: Paclitaxel,Gemcitabine,Sunitinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 1, 2012)
15
Original Estimated Enrollment  ICMJE
 (submitted: February 17, 2010)
58
Actual Study Completion Date  ICMJE November 2010
Actual Primary Completion Date December 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Age ? 18 years
  2. ECOG performance status 0-2
  3. Histologically confirmed and newly diagnosed breast cancer
  4. Documented HER2/neu non-overexpressing or non-amplified disease

    • 0-1+ by HER2 IHC or
    • HER2 gene non-amplification by HER2 FISH
  5. Clinical stage II or III operable breast cancer
  6. Axillary node positivity determined by cytology
  7. No prior hormonal, chemotherapy or radiotherapy is allowed
  8. No breast operation other than biopsy to make diagnosis is allowed
  9. Adequate hematologic, hepatic and renal function

    • Absolute neutrophil count ? 1,500/?L
    • Hemoglobin ? 10.0 g/dL
    • Platelet ? 100,000/?L
    • 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
  10. Adequate cardiac function LVEF ? 50% and within the institutional range of normal as measured by echocardiogram or MUGA scan within 4 weeks of enrollment
  11. Women of childbearing potential must have a negative urine pregnancy test within 7 days prior to registration
  12. Normal mental function to understand and sign the consent

Exclusion Criteria:

  1. Patients with metastatic breast cancer
  2. Patients who received hormonal, chemotherapy or radiotherapy for breast cancer
  3. Patients who underwent surgery for breast cancer
  4. Patients with T2N0, or inflammatory (T4d) breast cancer
  5. Patients who have history of cancer other than in situ uterine cervix cancer or nonmelanotic skin cancer
  6. 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)
  7. 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
  8. Ongoing cardiac dysrhythmias of grade ?2, atrial fibrillation of any grade, or QTc interval >470 msec.
  9. Hypertension that cannot be controlled by medications (>150/100 mmHg despite optimal medical therapy)
  10. Current treatment with therapeutic doses of Coumadin (low dose Coumadin up to 2 mg po daily for deep vein thrombosis prophylaxis is allowed).
  11. Known HIV infection
  12. 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.
  13. 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.
Sex/Gender  ICMJE
Sexes Eligible for Study:Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Korea, Republic of
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01070706
Other Study ID Numbers  ICMJE NCCCTS-08-369
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Jungsil Ro, National Cancer Center, Korea
Study Sponsor  ICMJE Jungsil Ro
Collaborators  ICMJE
  • Pfizer
  • HK inno.N Corporation
Investigators  ICMJE
Principal Investigator:Jungsil RoChief, Center for Breast Cancer, National Cancer Center, Korea
PRS Account National Cancer Center, Korea
Verification Date January 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP