Study Of Sunitinib With Capecitabine In Breast Cancer

• ClinicalTrials.gov Identifier: NCT00662025
• Recruitment Status: Completed
• First Posted: April 21, 2008
• Results First Posted: October 13, 2010
• Last Update Posted: May 27, 2013
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Study Description

Brief Summary:

To evaluate efficacy, safety and pharmacokinetics of sunitinib plus Capecitabine in Japanese patients with advanced/metastatic breast cancer.

Condition or disease	Intervention/treatment	Phase
Advanced/Metastatic Breast Cancer	Drug: Capecitabine; Drug: Sunitinib	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 63 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study Of Sunitinib Malate In Combination With Capecitabine In Patients With Advanced Or Metastatic Breast Cancer
• Study Start Date: April 2008
• Actual Primary Completion Date: December 2009
• Actual Study Completion Date: May 2012

Arms and Interventions

Arm	Intervention/treatment
Experimental: 1	Drug: Capecitabine; Capecitabine 1000 mg/m2, twice daily, for 2 consecutive weeks, followed by a 1-week rest period and given as 3-week cycles; Drug: Sunitinib; Sunitinib 37.5 mg daily, continuous dosing

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Objective Response Based on Data Review Committee's Assessment [ Time Frame: Day 1 of Cycle 2, every 6 weeks after Cycle 2, and at the end of Cycle 8. ]
   Number of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors version 1.0 (RECIST). CR is defined as disappearance of all target and non-target lesions. PR is defined as ≥30% decrease in sum of the longest dimensions (LDs) of the target lesions taking as reference the baseline sum LD according to RECIST. Confirmed responses are those that persist on repeat evaluation ≥4 weeks after initial documentation of response.

Secondary Outcome Measures :

1. Number of Participants With Objective Response Based on Investigator's Assessment [ Time Frame: Day 1 of Cycle 2, every 6 weeks after Cycle 2, and at the end of study. ]
   Number of participants with objective response based on assessment of confirmed CR or confirmed PR according to RECIST. CR is defined as disappearance of all target and non-target lesions. PR is defined as ≥30% decrease in sum of the LDs of the target lesions taking as reference the baseline sum LD according to RECIST. Confirmed responses are those that persist on repeat evaluation ≥4 weeks after initial documentation of response.
2. Number of Participants With Clinical Benefit Response (CBR) Based on Data Review Committee's Assessment [ Time Frame: Day 1 of Cycle 2, every 6 weeks after Cycle 2, and at the end of Cycle 8. ]
   Number of participants with confirmed CR, PR or stable disease (SD) for at least 24 weeks on study according to RECIST. CR is defined as disappearance of all target and non-target lesions. PR is defined as ≥30% decrease in sum of the LDs of the target lesions taking as a reference the baseline sum LD according to RECIST. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease taking as reference smallest sum of LDs since treatment started.
3. Number of Subjects With CBR Based on Investigator's Assessment [ Time Frame: Day 1 of Cycle 2, every 6 weeks after Cycle 2, and at the end of study. ]
   Number of participants with confirmed CR, PR or SD for at least 24 weeks on study according to RECIST. CR is defined as disappearance of all target and non-target lesions. PR is defined as ≥30% decrease in sum of the LDs of the target lesions taking as a reference the baseline sum LD according to RECIST. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease taking as reference smallest sum of LDs since treatment started.
4. Progression-Free Survival (PFS) [ Time Frame: Day 1 of Cycle 2, every 6 weeks after Cycle 2, and at the end of Cycle 8. Up to 28 days after the last administration of the study drug. ]
   Based on Data Review Committee's Assessment. PFS is defined as the time from the start of study treatment to first documentation of objective tumor progression, or to death on study due to any cause, whichever occurred first.
5. Time to Tumor Progression (TTP) [ Time Frame: Day 1 of Cycle 2, every 6 weeks after Cycle 2, and at the end of Cycle 8. Up to 28 days after the last administration of the study drug. ]
   Based on Data Review Committee's Assessment. TTP is defined as the time from the start of study treatment to first documentation of objective tumor progression.
6. Duration of Objective Tumor Response (DR) [ Time Frame: Day 1 of Cycle 2, every 6 weeks after Cycle 2, and at the end of Cycle 8. Up to 28 days after the last administration of the study drug. ]
   Based on Data Review Committee's Assessment. DR is defined as the time from the first documentation of objective tumor response (confirmed CR or PR) to the first documentation of disease progression or to death due to cancer, whichever occurred first. CR is defined as disappearance of all target and non-target lesions. PR is defined as ≥30% decrease in sum of the LDs of the target lesions taking as reference the baseline sum LD according to RECIST. Confirmed responses are those that persist on repeat evaluation ≥4 weeks after initial documentation of response.
7. Time to Objective Tumor Response (TTR) [ Time Frame: Day 1 of Cycle 2, every 6 weeks after Cycle 2, and at the end of Cycle 8. Up to 28 days after the last administration of the study drug. ]
   Based on Data Review Committee's Assessment. TTR is defined as the time from the start of study treatment to first documentation of objective tumor response (confirmed CR or PR). CR is defined as disappearance of all target and non-target lesions. PR is defined as ≥30% decrease in sum of the LDs of the target lesions taking as reference the baseline sum LD according to RECIST. Confirmed responses are those that persist on repeat evaluation ≥4 weeks after initial documentation of response.
8. Overall Survival (OS) [ Time Frame: A survival survey was conducted at least every 6 months after the completion of study treatment or withdrawal from the study. ]
   OS is defined as the time from the start of study treatment to death due to any cause. OS data is censored on the last day they were known to be alive in the absence of confirmation of death.
9. Trough Plasma Concentration (Ctrough) for Sunitinib, SU012662, and Total Drug (Sunitinib+SU012662) [ Time Frame: Days 14 and 15 of Cycle 1 ]

   SU012662 is a metabolite of sunitinib. Trough plasma concentration (Ctrough) means the concentration prior to study drug administration.

   The Ctrough for total drug (sunitinib+SU012662) was calculated as the mean of the Ctrough of total drug from individual participant.

10. Tmax for Sunitinib, SU012662, and Total Drug (Sunitinib+SU012662) [ Time Frame: Days 14 and 15 of Cycle 1 ]

    SU012662 is a metabolite of sunitinib. Tmax means a time to first occurrence of maximum observed plasma concentration (Cmax).

    The Tmax for total drug (sunitinib+SU012662) was calculated as the median of the Tmax of total drug from individual participant.

11. Cmax for Sunitinib, SU012662, and Total Drug (Sunitinib+SU012662) [ Time Frame: Days 14 and 15 of Cycle 1 ]

    SU012662 is a metabolite of sunitinib. Cmax means a maximum observed plasma concentration.

    The Cmax for total drug (sunitinib+SU012662) was calculated as the mean of the Cmax of total drug from individual participant.

12. AUC(0-24) for Sunitinib, SU012662, and Total Drug (Sunitinib+SU012662) [ Time Frame: Days 14 and 15 of Cycle 1 ]

    SU012662 is a metabolite of sunitinib. AUC(0-24) means an area under the plasma concentration time curve from time zero to 24 hours post-dose.

    The AUC(0-24) for total drug (sunitinib+SU012662) was calculated as the mean of the AUC(0-24) of total drug from individual participant.

13. Tmax for Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR and 5-FU) [ Time Frame: Day 14 of Cycle 1 ]

    Tmax means a time to first occurrence of maximum observed plasma concentration (Cmax).

    5'-DFCR = 5'-deoxy-5-fluorocytidine, 5'-DFUR = 5'-deoxy-5-fluorouridine, 5-FU = 5-fluorouracil

14. Cmax for Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR and 5-FU) [ Time Frame: Day 14 of Cycle 1 ]
    Cmax means a maximum observed plasma concentration. 5'-DFCR = 5'-deoxy-5-fluorocytidine, 5'-DFUR = 5'-deoxy-5-fluorouridine, 5-FU = 5-fluorouracil
15. AUC(0-inf) for Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR and 5-FU) [ Time Frame: Day 14 of Cycle 1 ]

    AUC(0-inf) means an area under the plasma concentration time curve from time zero to Infinity.

    5'-DFCR = 5'-deoxy-5-fluorocytidine, 5'-DFUR = 5'-deoxy-5-fluorouridine, 5-FU = 5-fluorouracil

16. t1/2 for Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR and 5-FU) [ Time Frame: Day 14 of Cycle 1 ]
    t1/2 means a terminal phase half-life. 5'-DFCR = 5'-deoxy-5-fluorocytidine, 5'-DFUR = 5'-deoxy-5-fluorouridine, 5-FU = 5-fluorouracil

Eligibility Criteria

• Ages Eligible for Study: 20 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Histologically- or cytologically-proven diagnosis of breast adenocarcinoma that is not amenable to surgery, radiation, or combined modality therapy with curative intent
• Measurable disease as per RECIST. Measurable lesions that have been previously irradiated will not be considered target lesions unless increase in size has been observed following completion of radiation therapy.
• Prior treatment with an anthracycline and a taxane in the neoadjuvant, adjuvant or metastatic disease settings.

Exclusion Criteria:

• Histology of inflammatory carcinoma with no other measurable disease. Patients with histology of inflammatory carcinoma are allowed on study if they have measurable disease.
• Brain metastases, spinal cord compression, or carcinomatous meningitis, or leptomeningeal disease.
• Prior treatment with 5-fluorouracil (5-FU) and 5-FU derivatives such as Furtulon (5'-DFUR), Futraful/ Sunfural (tegafur), UFT/UFT-E (tegafur/uracil), TS-1 (tegafur/gimeracil/oteracil) or Mifurol (carmofur) in metastatic disease setting

Contacts and Locations

Locations

Japan

Pfizer Investigational Site

Anjo-city, Aichi, Japan

Pfizer Investigational Site

Nagoya, Aichi, Japan

Pfizer Investigational Site

Okazaki-City, Aichi, Japan

Pfizer Investigational Site

Toyoake, Aichi, Japan

Pfizer Investigational Site

Matsuyama-shi, Ehime, Japan

Pfizer Investigational Site

Kure, Hiroshima, Japan

Pfizer Investigational Site

Morioka, Iwate, Japan

Pfizer Investigational Site

Yokohama, Kanagawa, Japan

Pfizer Investigational Site

Sakai, Osaka, Japan

Pfizer Investigational Site

Bunkyo-ku, Tokyo, Japan

Pfizer Investigational Site

Koto-ku, Tokyo, Japan

Pfizer Investigational Site

Chiba, Japan

Pfizer Investigational Site

Fukuoka, Japan

Pfizer Investigational Site

Kagoshima, Japan

Pfizer Investigational Site

Kyoto, Japan

Pfizer Investigational Site

Niigata, Japan

Pfizer Investigational Site

Osaka, Japan

Sponsors and Collaborators

Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

More Information

Additional Information:

To obtain contact information for a study center near you, click here. 

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT00662025
• Other Study ID Numbers: A6181163
• First Posted: April 21, 2008
• Results First Posted: October 13, 2010
• Last Update Posted: May 27, 2013
• Last Verified: May 2013

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Capecitabine; Sunitinib; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Physiological Effects of Drugs; Growth Inhibitors; Protein Kinase Inhibitors; Enzyme Inhibitors