Patient case: 45-year-old female with cervical cancer; genetic feature: ERBB2 (S310Y)

Clinical trial: ErbB2 Over-expressing Metastatic Breast Cancer Study Using Paclitaxel, Trastuzumab, and Lapatinib

Summary: Patients will be randomised to a 1:1 ratio to receive either paclitaxel 80 mg/m2 IV weekly for three weeks of a four week cycle, trastuzumab 4 mg/kg loading dose and 2 mg/kg weekly IV, and oral lapatinib 1000 mg QD or paclitaxel 80 mg/m2 IV weekly for three weeks of a four week cycle, trastuzumab 4 mg/kg loading dose and 2 mg/kg weekly IV plus placebo. The primary objective of this study is to evaluate and compare time to progression (TTP). Secondary objectives will be to evaluate and compare the two treatment arms with respect to: overall response rates, clinical benefit, time to response, duration of response, progression-free survival, and overall survival. The study will first enroll an open label safety cohort of 20 patients to assess the tolerability of the triplet combination.


Eligibility: Inclusion criteria:
  -  Histologically confirmed invasive breast cancer with stage IV disease If trastuzumab was administered in the adjuvant setting, >12 months must have elapsed since discontinuation of trastuzumab therapy
  -  If a taxane was administered in the neoadjuvant or adjuvant setting, progression must have occurred 12 months after completion of this treatment
  -  Had tumors that overexpress ErbB2 (Immunohistochemistry 3+ or Fluorescent in-situ hybridisation gene amplification)
  -  Patients must have tumor tissue available for central testing Measurable lesion(s)
  -  Subjects must be females of at least 18 years Non-childbearing potential or Childbearing potential but using adequate contraception
  -  Radiotherapy to a limited area other than the sole site of measurable and assessable disease is allowed; however, patients must have completed treatment and recovered from all acute treatment-related toxicities prior to administration of the first dose of study medication
  -  Bisphosphonate therapy for bone metastases is allowed; however, treatment must be initiated prior to the first dose of randomized therapy. Prophylactic use of bisphosphonates in patients without bone disease is not permitted, except for the treatment of osteoporosis
  -  Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 1
  -  For those patients whose disease is estrogen receptor positive+ and/or progesterone receptor + one the following criteria should be met: Patients with visceral disease that requires chemotherapy (eg., patients with liver or lung metastases) or Rapidly progressing/life threatening disease, as determined by the investigator or Patients who received hormonal therapy and are no longer benefiting from this therapy;
  -  Able to swallow and retain oral medication
  -  Cardiac ejection fraction within institutional range of normal
  -  Patient must have adequate organ function
  Exclusion criteria:
  -  Pregnant or lactating females;
  -  Received prior chemotherapy, immunotherapy, biologic therapy, or anti-ErbB1/ErbB2 therapy for metastatic disease, prior hormonal therapy is permitted but must be discontinued a minimum of 7 days prior to randomization; Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel.
  -  Patients with ulcerative colitis are also excluded;
  -  History of other malignancy; however, patients who have been disease-free for five years, or patients with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible;
  -  Concurrent disease or condition that would make the patient inappropriate for study participation, or any serious medical disorder that would interfere with the patient's safety;
  -  Unresolved or unstable, serious toxicity from prior administration of another investigational drug and/or of prior cancer treatment;
  -  Peripheral neuropathy of Grade 2 or greater;
  -  Active or uncontrolled infection;
  -  Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent;
  -  Known history of uncontrolled or symptomatic angina, arrhythmias, conduction abnormalities or congestive heart failure;
  -  Known history or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis;
  -  Concurrent cancer therapy (chemotherapy, radiation therapy, immunotherapy, biologic therapy, hormonal therapy); Concurrent treatment with an investigational agent or participation in another clinical trial;
  -  Concurrent treatment with any medication on the prohibited medications list.
  -  Used an investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the first dose of treatment. Hormonal therapy needs to be discontinued at least 7 days before the first dose of treatment.
  -  Prior therapy with an ErbB2 inhibitor, other than trastuzumab in the adjuvant setting;
  -  A known immediate or delayed hypersensitivity reaction to drugs chemically related to lapatinib or excipients;
  -  A known immediate or delayed hypersensitivity reaction to drugs chemically related to paclitaxel or excipients;
  -  A known immediate or delayed hypersensitivity reaction to drugs chemically related to trastuzumab or excipients;
  -  Non compliance with any of the screening procedures

Relevance to patient case: not relevant