Clinical trial NCT02730481: A Study to Evaluate the Safety, Tolerability, MTD, PK, and Activity of Oraxol in Subjects w Adv. Malignancies
Official title: A Dose Regimen-Finding Study to Evaluate the Safety, Tolerability, Maximum Tolerated Dose, Pharmacokinetics, and Activity of Oraxol in Subjects With Advanced Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumor
Lead sponsor: Athenex, Inc.
Sponsor class: INDUSTRY
First posted: 2016-04-06
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a multicenter, open-label, safety study. Eligible subjects will be adults with advanced malignancies. The study includes a pretreatment and treatment phase. The pretreatment phase consists of screening and baseline periods. The treatment phase consists of 4-week treatment periods and a follow-up period.


Eligibility criteria: Inclusion Criteria:

1. Signed written informed consent
2. ≥18 years of age
3. 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
4. Measurable disease as per RECIST v1.1 criteria
5. Adequate hematologic status as demonstrated by not requiring transfusion support or granulocyte-colony stimulating factor (G-CSF) to maintain: ANC ≥1500 cells/mm3, Platelet count ≥100 x 109/L, Hemoglobin ≥9 g/dL
6. Adequate liver function as demonstrated by:Total bilirubin of ≤1.5 mg/dL or ≤2.0 mg/dL for subjects with liver metastasis, Alanine aminotransferase ≤3 x upper limit of normal (ULN) or ≤5 x ULN if liver metastasis is present, Alkaline phosphatase ≤3 x ULN or ≤5 x ULN if bone or liver metastasis is present
7. Adequate renal function as demonstrated by serum creatinine ≤1.5 x ULN or creatinine clearance calculation ≥60 mL/min as calculated by the Cockcroft and Gault formula
8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
9. Life expectancy of at least 3 months
10. Women must be postmenopausal (\>12 months without menses) or surgically sterile (ie, by hysterectomy and/or bilateral oophorectomy) or must be using effective contraception (ie, oral contraceptives, intrauterine device, double barrier method of condom and spermicide) and agree to continue use of contraception for 30 days after their last dose of study drug.
11. Sexually active male subjects must use a barrier method of contraception during the study and agree to continue the use of male contraception for at least 30 days after the last dose of study drug.

Exclusion Criteria:

1. Have not recovered to ≤ Grade 1 toxicity from previous anticancer treatments or previous investigational products (IPs)
2. Received IPs within 30 days or 5 half lives of the first study dosing day
3. Are currently receiving other medications or radiation intended for the treatment of their malignancy
4. Women of childbearing potential who are pregnant or breastfeeding
5. Currently taking a concomitant medication
6. Require therapeutic use of anticoagulation medications
7. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, myocardial infarction within the last 6 months, unstable angina pectoris, cardiac arrhythmia, chronic pulmonary disease requiring oxygen, known bleeding disorders, or any concomitant illness or social situation that would limit compliance with study requirements
8. 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
9. History of hypersensitivity to paclitaxel, not attributed to a hypersensitivity type reaction to Cremophor

Primary outcomes:
measure: Maximum tolerated dose (MTD) of Oraxol
timeFrame: 20 weeks
Secondary outcomes:
measure: Evaluate tumor response
timeFrame: At baseline and every 8 weeks through study completion, approximately 24 months
measure: Number of Participants with abnormal laboratory values and/or adverse events that are related to treatment
timeFrame: 4 weeks
measure: The amount of Oraxol in the blood stream
timeFrame: 3 weeks
measure: The recommended Phase 2 dose of paclitaxel as Oraxol
timeFrame: 24 months
Other outcomes:
Locations:
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: San Antonio
country: United States
facility: Cancer Therapy &Research Center @ UTHSCSA
state: Texas
Study officials:
affiliation: Kinex Pharmaceuticals Inc.
name: E D Kramer, MD
role: STUDY_DIRECTOR
References: