Overview
This is a single arm, open-label, lead in phase Ib dose confirmation, followed by phase II study with 2 parallel study cohorts.
Description
Phase Ib Patients will be treated with twice-daily dosing of FTD/TPI in a 3+3 dose escalation design Phase II
Oral FTD/TPI at RP2D will be administered until disease progression, intolerable toxicity or patient withdrawal.
2 parallel cohorts of patients will be enrolled : Cohort A : patients with prior exposure to fluoropyrimidines Cohort B : patients without prior exposure to fluoropyrimidines
Eligibility
Inclusion Criteria:
- Age ≥ 21 years.
- Histological or cytological diagnosis of breast carcinoma.
- ECOG 0-2.
- HER2 negative tumor (IHC 0 -1+ or IHC 2+ and confirmed on HER2 FISH to be negative based on histological report).
- Patients with HER2 positive tumor may be enrolled if they have failed at least two lines of anti-HER2 based therapies in the metastatic setting, or are intolerant to trastuzumab
- Any hormone receptor status.
- Any number of lines of prior palliative endocrine therapy for patients with hormone receptor positive cancer.
- Has measureable or evaluable disease based on RECIST 1.1 criteria
- Estimated life expectancy of at least 12 weeks.
- Has documented progressive disease from last line of therapy.
- Has recovered from acute toxicities from prior anti-cancer therapies
- Adequate organ function including the following:
oBone marrow: (I) Absolute neutrophil (segmented and bands) count (ANC) ≥1.5 x 109/L (ii) Platelets ≥100 x 109/L (ii) Hemoglobin ≥8 x 109/L oHepatic: (I)Bilirubin ≤ 1.5 x upper limit of normal (ULN), (ii)ALT or AST ≤ 2.5x ULN, (or ≤ 5 X with liver metastases) oRenal: (I) Creatinine ≤1.5x ULN - Signed informed consent from patient or legal representative. - Able to comply with study-related procedures. - Prior therapy (patients enrolled in phase Ib may be enrolled if they fulfil prior therapy criteria for either Cohort A or Cohort B) - Cohort A only: Has received at least 2 lines of palliative systemic therapy, including prior fluropyrimidines (capecitabine, TS-1 or 5-fluorouracil) in the palliative setting, or in the adjuvant setting; patients who have only prior exposure to adjuvant fluoropyrimidines must have relapsed within 12 months of completing adjuvant fluoropyrimidines - Cohort B only: Any number of prior lines of palliative chemotherapy and has not received fluoropyrimidines (capecitabine, TS-1 or 5-fluorouracil) in the palliative setting or in the adjuvant setting; patients who have prior exposure to adjuvant fluoropyrimidines are eligible if they have relapsed 12 months from completion of adjuvant fluoropyrimidines. Exclusion Criteria: - Treatment within the last 30 days with any investigational drug. - Concurrent administration of any other tumour therapy, including cytotoxic chemotherapy, hormonal therapy, and immunotherapy. - Major surgery within 28 days of study drug administration. - Active infection that in the opinion of the investigator would compromise the patient's ability to tolerate therapy. - Pregnancy. - Breast feeding. - Serious concomitant disorders that would compromise the safety of the patient or compromise the patient's ability to complete the study, at the discretion of the investigator. - Active bleeding disorder or bleeding site. - Non-healing wound. - Poorly controlled diabetes mellitus. - Second primary malignancy that is clinically detectable at the time of consideration for study enrollment. - Symptomatic brain metastasis. - History of significant neurological or mental disorder, including seizures or dementia. - Unable to comply with study procedures Phase Ib lead-in can recruit patients who fulfil criteria for either Cohort A or Cohort B AND all other inclusion/exclusion criteria