A Multicenter, Open-Label, Noncomparative Phase I Clinical and Pharmacokinetic Study of Oral TAK-285 in Patients With Advanced Cancer
- The subject has a histologically confirmed advanced non-hematologic malignancy.
- The subject has a chemotherapy-free interval of at least 4 weeks prior to first dose
of study drug.
- The subject is intolerant of, is not a candidate for, or the subject's disease is
refractory to established therapy known to provide clinical benefit for their
- A female subject of childbearing potential who is sexually active agrees to use
adequate contraception from Screening throughout the duration of the study, and for
30 days after the last dose of study drug. Male subjects should agree to use
contraception for the duration of the study, and for 30 days after the last dose of
- The subject has a life expectancy of greater than 12 weeks.
- The subject has an Eastern Cooperative Oncology Group performance status of 0 to 2.
- The subject has the ability to swallow and retain oral medication
- The subject's most recent test values within 2 weeks before the date of entry meet
the following standards:
- Bone marrow function:
- Absolute neutrophil count ≥1500/mm3
- Hemoglobin ≥9.0g/dL, platelet count ≥100,000/mm3.
- Liver function:
- Total bilirubin ≤1.5 times the upper limit of the standard value of each
- Aspartate aminotransferase and alanine aminotransferase ≤2.5 times the
upper limit of the standard value of each institution.
- Renal function:
- Serum creatinine ≤1.5 times the upper limit of the standard value of each
- In the recommended phase 2 dose Cohort, the subject has an accessible tumor for
biopsy and is willing to undergo 2 tumor biopsies.
- In the recommended phase 2 dose Cohort, the subject has at least 1 measurable lesion
based on the treatment assessment standards for solid tumors.
- In the recommended phase 2 dose Cohort, the subject has a tumor that expresses EGFR
and/or overexpresses erbB2.
- The subject has a symptomatic brain metastasis.
- The subject has an uncontrollable pleural effusion, ascitic fluid, or pericardial
- The subject has active gastrointestinal bleeding as evidenced by either hematemesis
- The subject has acute gastrointestinal ulcers.
- The subject has been treated with a small molecule inhibitor of EGFR or HER2 (except
- The subject has a history of any cancer other than the present condition (except
nonmelanoma skin cancer or carcinoma in situ of the cervix), unless in complete
remission and off all therapy for that disease for a minimum of 3 years.
- The subject has significant cardiovascular impairment (history of New York Heart
Association class III or IV) or a history of myocardial infarction or unstable angina
within the past 6 months prior to study drug treatment.
- The subject has a severe disease (other than cancer) that will likely affect the
prospects of survival or a history that will make it difficult to appropriately
manage and follow his or her progress in accordance with the protocol (serious organ
disorder, mental illness, drug abuse, alcohol dependency, etc.).
- The subject requires prohibited treatment (drug, surgery or radiotherapy for
treatment of malignant tumor, drugs that could interact with TAK-285) except for
radiotherapy of limited area (<20% of total bone marrow) in order to relieve the
symptoms from symptomatic bone metastasis.
- The subject who has been treated with a drug, which inhibits or induces Cytochrome
P450 3A4 within 1 week prior to the start of treatment with the investigational drug.
- The subject is pregnant or breast feeding.
- The subject has participated in another clinical study/postmarketing clinical study
within 4 weeks prior to the start of treatment with TAK-285.
- The subject is currently taking excluded medications, including:
- Concurrent anticancer therapy with agents other than TAK-285.
- The following prohibited medications and substances should not be used for at
least 7 days prior to the start of the study and throughout completion:
- Strong CYP3A4 inhibitors
- Human immunodeficiency virus protease inhibitors
- macrolide antibiotics (excluding azithromycin)
- Strong CYP3A4 inducers
- St. John's wort
- Medications and devices containing hormones such as oral contraceptives.