Study Of SU011248 In Combination With Docetaxel And Trastuzumab In Patients With Advanced Breast Cancer HER-2 Positive

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00372424
First received: September 5, 2006
Last updated: December 21, 2012
Last verified: December 2012
  Purpose

This is an exploratory trial evaluating the tolerability and preliminary anti-tumor activity of SU011248 combined with docetaxel and trastuzumab in patients with locally recurrent or metastatic breast cancer over-expressing Her-2, who have not received chemotherapy treatment in the advanced disease setting.


Condition Intervention Phase
Breast Cancer
Drug: Herceptin
Drug: Sunitinib
Drug: Taxotere
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Explorative Study Of The Tolerability Of SU011248 In Combination With Docetaxel And Trastuzumab As First-Line Treatment In Patients With Breast Cancer Over-Expressing HER-2

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) [ Time Frame: From screening until 28 days post last dose of study drug ] [ Designated as safety issue: Yes ]
    An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A SAE was an AE resulting in any of following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state.


Secondary Outcome Measures:
  • Percentage of Participants With Objective Response (OR) [ Time Frame: Baseline, assessed every 6 weeks starting from Day1 of Cycle 3 up to end of treatment (Day 1344) ] [ Designated as safety issue: No ]
    Percentage of participants with objective response based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed responses are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. CR are defined as disappearance of all target lesions. PR are those with at least 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions.

  • Progression-free Survival (PFS) [ Time Frame: Baseline, assessed every 6 weeks starting from Day1 of Cycle 3 up to end of treatment (Day 1344) ] [ Designated as safety issue: No ]
    Time in weeks from start of study treatment to first documentation of objective tumor progression or death due to any cause. PFS was calculated as (first event date minus the date of first dose of study medication plus 1) divided by 7. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease [PD]), or from adverse event (AE) data (where the outcome was "Death").

  • Duration of Response (DR) [ Time Frame: Baseline, assessed every 6 weeks starting from Day1 of Cycle 3 up to end of treatment (Day 1344) ] [ Designated as safety issue: No ]
    Time in weeks from the first documentation of objective tumor response to objective tumor progression or death due to any cancer. Duration of tumor response was calculated as (the date of the first documentation of objective tumor progression or death due to cancer minus the date of the first CR or PR that was subsequently confirmed plus 1) divided by 7. DR was calculated for the subgroup of participants with a confirmed objective tumor response.

  • Plasma Trough Concentrations (Ctrough) of SU011248 (Sunitinib), SU012662 (Sunitinib Metabolite) and Total Drug (SU011248+SU012662) [ Time Frame: Pre-dose (0 hours [H]) on Day 1 and Day 15 of Cycle 2, 4, 6 and additionally Day 15 of Cycle 1 ] [ Designated as safety issue: No ]
    Ctrough = the concentration prior to study medication administration. Ctrough was calculated for SU011248 (Sunitinib), SU012662 (Sunitinib metabolite) and total drug (SU011248+SU012662). Concentration values below the lower limit of quantification were taken as zero.

  • Maximum Observed Plasma Concentration (Cmax) of Docetaxel [ Time Frame: End of infusion (1 H) on Day 1 of Cycle 1, 2, 4 and 6 ] [ Designated as safety issue: No ]
    Concentration values below the lower limit of quantification were taken as zero.

  • Plasma Trough Concentrations (Ctrough) of Trastuzumab [ Time Frame: Weekly trastuzumab: Pre-dose (0 H) on Day 1 and 15 of Cycle 1, 2, 4 and 6; 3-weekly trastuzumab: Pre-dose (0 H) on Day 1 of Cycle 1, 2, 4 and 6 ] [ Designated as safety issue: No ]
    Ctrough = the concentration prior to study medication administration.


Other Outcome Measures:
  • Maximum Observed Plasma Concentration (Cmax) of Paclitaxel [ Time Frame: End of infusion (1 H) on Day 1 of Cycle 1, 2, 4 and 6 ] [ Designated as safety issue: No ]

Enrollment: 26
Study Start Date: December 2006
Study Completion Date: September 2011
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Combination of SU011248 (37.5 mg once daily [Schedule 2/1]) with docetaxel (75 mg/m2 every 3 weeks) and trastuzumab (therapeutic dose)
Drug: Herceptin
Trastuzumab will be administered intravenously on Day 1 before docetaxel - loading dose of 4 mg/kg over 90-minute on Day 1 followed by weekly maintenance doses of 2 mg/kg on Days 1, 8, 15 given as 30-minute infusions if the initial loading dose was well tolerated. Loading dose of 8 mg/kg over 90-minute on Day 1 followed by 3-weekly maintenance doses of 6 mg/kg given as 90-minute infusions. The administration of 6 mg/kg will be repeated on Day 1 every 3 weeks.
Other Name: trastuzumab
Drug: Sunitinib
SU011248 will be administered at 37.5 mg once daily for 2 weeks every 3 weeks (Schedule 2/1) starting from Day 2, when in combination with docetaxel. SU011248 will be administered at the starting dose of 37.5 mg daily in a continuous regimen when docetaxel is discontinued.
Other Name: Sutent
Drug: Taxotere
The starting dose of docetaxel will be 75 mg/m2 every 3 weeks, administered on Day 1 of each cycle as a 1-hour IV infusion.
Other Name: docetaxel

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Breast cancer with evidence of unresectable, locally recurrent, or metastatic disease.
  • Tumors over-expressing Her-2
  • Candidate for treatment with docetaxel/trastuzumab

Exclusion Criteria:

  • Histology of inflammatory carcinoma
  • AST and/or ALT >1.5 x ULN concomitant with ALP >2.5 x ULN
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00372424

Locations
Belgium
Pfizer Investigational Site
Bruxelles, Belgium, 1000
Pfizer Investigational Site
Bruxelles, Belgium, 1200
Pfizer Investigational Site
Charleroi, Belgium, 6000
Pfizer Investigational Site
Sint-Niklaas, Belgium, 9100
Pfizer Investigational Site
Wilrijk, Belgium, 2610
Italy
Pfizer Investigational Site
Meldola, FC, Italy, 47014
Pfizer Investigational Site
Milano, Italy, 20132
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided by Pfizer

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00372424     History of Changes
Other Study ID Numbers: A6181113
Study First Received: September 5, 2006
Results First Received: September 28, 2012
Last Updated: December 21, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
Breast cancer over-expressing HER2. First-line treatment with sunitinib/docetaxel/trastuzumab.

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Docetaxel
Trastuzumab
Sunitinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors

ClinicalTrials.gov processed this record on August 20, 2014