Clinical Trials

Core Inclusion Criteria:

• Signed written informed consent.
• Age ≥ 18 years old.
• Histologically or cytologically confirmed solid tumor that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective.
• Docetaxel monotherapy is a reasonable treatment in the judgement of the Investigator.
• Able to swallow oral medication as an intact dosage form.
• Adequate hematologic status as demonstrated by not requiring transfusion support or granulocyte-colony stimulating factor (G-CSF) to maintain an absolute neutrophil count (ANC) ≥ 1500 cells/mm^3, platelet count ≥ 100 x 10^9/L, or hemoglobin (Hgb) ≥ 9 g/dL.
• Adequate liver function as demonstrated by a total bilirubin of < upper limit of normal (ULN), aspartate transaminase (AST) and alanine aminotransferase (ALT) ≤ 1.5 × ULN, alkaline phosphatase (ALP) ≤ 2.5 x ULN or < 5 x ULN if bone metastases are present, and normal serum albumin.
• Adequate renal function as demonstrated by serum creatinine ≤ 1.5 x ULN or creatinine clearance>60 mL/min as calculated by the Cockroft and Gault formula.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• Life expectancy of at least 3 months.
• Willing to fast for 6 hours before and 2 hours after Oradoxel administration.
• Sexually active male subjects including men who are sterile (including vasectomy confirmed by post vasectomy semen analysis) must agree to use a condom with spermicide and to not donate sperm from the time of screening until 6 months after the last dose of study drug.

Core Exclusion Criteria:

• Currently taking a prohibited concomitant medication, other than a premedication, that are/is:
  • Strong inhibitors (e.g., ketoconazole) or inducers (e.g., rifampicin or St. John's Wort) of CYP3A45 (within 2 weeks prior to the start of dosing in the study);
  • Strong P-gp inhibitors or inducers.  Subjects who are taking such medications but who are otherwise eligible may be enrolled if they discontinue the medication ≥ 1 week before dosing and remain off that medication through the end of PK sampling after the administration of the second study treatment;
  • An oral medication with a narrow therapeutic index known to be a P-gp substrate within 24 hours prior to start of dosing in the study.
• Unresolved toxicity from prior chemotherapy (subjects must be recovered to ≤ Grade 1 toxicity from previous anticancer treatments or previous investigational products.
• Planning to receive other medical, surgical, or radiological cancer treatments during the course of this study.
• Received investigational agents within 14 days or 5 half-lives prior to the first study dosing day, whichever is longer.
• Require therapeutic use of anticoagulants.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, clinically significant myocardial infarction within the last 6 months, unstable angina pectoris, clinically significant cardiac arrhythmia, bleeding disorder, chronic pulmonary disease requiring oxygen, or psychiatric illness/social situations that would limit compliance with study requirements.
• Major surgery to the upper gastrointestinal (GI) tract, or have a history of GI disease or other medical condition that, in the opinion of the Investigator, may interfere with oral drug absorption.
• A known history of allergy to docetaxel, Cremophor or polysorbate 80 (Tween 80).
• Evidence of fluid retention at screening (including, for example, peripheral edema, pleural effusion, or ascites on physical or radiological examination) or history of severe capillary leak syndrome.
• Any other condition which the Investigator believes would make participation in the study not acceptable.

Module 1 Inclusion Criteria:

In addition to the Core Inclusion Criteria listed above, subjects with solid malignancies other than mCRPC must meet the following criteria to be included in Module 1:

• Subjects have measurable disease as per RECIST v1.1 criteria or evaluable disease.
• Women of non-child bearing potential due to surgical sterilization (at least 6 weeks following surgical bilateral oophorectomy with or without hysterectomy or tubal ligation) confirmed by medical history or menopause (ie, no menstrual bleeding for more than 12 months in a woman aged ≥ 45 years), OR women of childbearing potential who test negative for pregnancy at time of enrollment based on serum pregnancy test must be using a highly effective method of contraception from the time of Screening until 6 months following the last dose of study drug.
  • Note: Highly effective methods of contraception that result in a low failure rate (i.e., <1% per year) when used consistently and correctly include combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, or transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, or implantable), intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomized partner, or sexual abstinence.
    True abstinence, when in line with the preferred and usual lifestyle of the subject, is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of study participation and for 6 months post- Oradoxel administration. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, and post-ovulation method) and withdrawal are not acceptable methods of contraception.

Module 1 Exclusion Criteria:

• There are no exclusion criteria in addition to the Core Exclusion Criteria listed above.

Module 2 Inclusion Criteria:

• In addition to the Core Inclusion Criteria listed above, subjects with mCRPC must meet the following criteria to be included in Module 2:
  • Subjects have measurable or evaluable mCRPC as per modified RECIST 1.1 based on PCWG3 criteria;
  • Subjects have a minimum PSA of 2.0 ng/mL.

Module 2 Exclusion Criteria:

• In addition to the Core Exclusion Criteria listed above, subjects who meet the following criterion will be excluded from the study:
  • Subjects who have had prior treatment with taxanes.