Phase 3
Completed N=537
Phase III Trial Comparing Capecitabine in Combination With Sorafenib or Placebo in the Treatment of Locally Advanced or Metastatic HER2-Negative Breast Cancer
Source: ClinicalTrials.gov NCT01234337 ↗Enrolled (actual)
537
Serious AEs
28.7%
Results posted
Sep 2015
Primary outcomePrimary: Progression-free Survival (PFS) Assessed by the Independent Review Panel According to Response Evaluation Criteria for Solid Tumors (RECIST) 1.1 — 166; 165 days — p==0.405618
Summary
The objective of this phase-III trial is to compare the efficacy and safety of sorafenib in combination with capecitabine versus capecitabine in combination with placebo in the treatment of subjects with locally advanced or metastatic HER2-negative breast cancer who are resistant to or have failed prior taxane and an anthracycline or for whom further anthracycline therapy is not indicated. After signing consent there can be up to 28 days before starting the treatment during which time a number of tests will be carried out which will include tumor evaluations and medical history. The following tests and evaluations will have to be done within 7 days of the start of treatment,on Day 1 of every cycle and at the end of study: Electrocardiogram, blood tests, patient quality of life questionnaires and a complete physical exam and vital signs. Treatment will be given in 21 day cycles with sorafenib/placebo to be taken every day for 21 days and capecitabine to be taken for the first 14 days. Patients will come in weekly for the first 6 weeks and then on Day1 for every cycle after the first 2 cycles. During the weekly visits the subjects will be check for any side effects and blood draws will happen for the study on Day 1 of each cycle. Subjects will be followed for overall survival.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Progression-free Survival (PFS) Assessed by the Independent Review Panel According to Response Evaluation Criteria for Solid Tumors (RECIST) 1.1 |
166; 165 | =0.405618 |
| SECONDARY Overall Survival (OS) |
575; 616 | =0.930088 |
| SECONDARY Time to Progression (TTP) by Central Review |
168; 165 | =0.2105 |
| SECONDARY Objective Response Rate (ORR) by Central Review |
13.5; 15.5 | =0.257412 |
| SECONDARY Disease Control Rate (DCR) by Central Review |
60.5; 58.3 | =0.284674 |
| SECONDARY Duration of Response (DOR) by Central Reader |
313; 290 | — |
Eligibility Criteria
Inclusion Criteria
- Age is >=18 years
- Subject has histologically or cytologically confirmed HER2-negative adenocarcinoma of the breast. HER2 status should be determined by an accredited laboratory
- Subject has locally advanced or metastatic disease; locally advanced disease must not be amenable to resection with curative intent. Must have measurable or non-measurable disease (according to RECIST [Response Evaluation Criteria for Solid Tumors] 1.1)
- All computer tomography (CT; with contrast) and magnetic resonance imaging (MRI) used to document disease must have been done = 4 weeks (28 days) before randomization. Start of study treatment is allowed within less than 28 days of the prior therapy provided that 5 half-lives of the prior treatment drug(s) have elapsed
- ECOG (Eastern Cooperative Oncology Group) performance status 0 or 1
- Adequate bone marrow, liver and renal function within 7 days prior to randomization
- All acute toxic effects of any prior treatment have resolved to NCI-CTCAE (National Cancer Institute-Common Terminology Criteria for Adverse Events) v4.0 Grade 1 or less
- Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to randomization
- Subjects (men and women) of childbearing potential must agree to use adequate contraception beginning at the signing of the ICF (Informed Consent Form) until at least 30 days after the last dose of study drug.
- Subject must be able to swallow and retain oral medication
Exclusion Criteria
- HER2 positive breast cancer
- Unknown hormone receptor status (estrogen and progesterone receptor).
- Subjects with bilateral breast cancer or a history of two distinct breast cancers.
- Subjects with inflammatory breast carcinoma.
- Subjects who have received no prior taxane and anthracycline for the treatment of breast cancer (either in adjuvant, neo-adjuvant or metastatic setting).
- Prior use of sorafenib or capecitabine
- Subjects considered by the treating investigator to be appropriate candidates for hormonal therapy as current treatment for locally advanced/metastatic breast cancer
- Subjects with locally advanced disease who are considered by the treating investigator to be appropriate candidates for radiation therapy as current treatment for locally advanced breast cancer
- Subjects with active brain metastases or leptomeningeal disease.
- Subjects with seizure disorder requiring medication.
- Radiation to any lesions Grade 2
- Subjects with a history of human immunodeficiency virus infection or current chronic or active hepatitis B or C infection.
- Subjects who have used strong CYP3A4 inducers (eg, phenytoin, carbamazepine, phenobarbital, St. John's Wort [Hypericum perforatum], dexamethasone at a dose of greater than 16 mg daily, or rifampin [rifampicin], and/or rifabutin) within 28 days before randomization.
- Subjects with any previously untreated or concurrent cancer that is distinct in primary site or histology from breast cancer
- Subjects with a history DHPD (Dihydropyrimidine dehydrogenase) reaction to fluropyrimidine or history of known or suspected allergy or hypersensitivity to any of the study drugs
- Presence of a non-healing wound, non-healing ulcer, or bone fracture
- Women pregnant or breast feeding
- Any condition which, in the investigator's opinion, makes the subject unsuitable for trial participation
Data sourced from ClinicalTrials.gov (NCT01234337). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.