Clinical Trials /

Ph1b Study of Oraxol in Comb. w. Ramucirumab in Patients w. Gastric, Gastro-esophageal, or Esophageal Cancers

NCT02970539

Description:

This is a nonrandomized, open-label, single group assignment, safety, tolerability and pharmacokinetic (PK) study to determine the MTD and optimal dosing regimen of Oraxol in combination with ramucirumab.

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Esophageal Adenocarcinoma
  • Gastric Adenocarcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Ph1b Study of Oraxol in Comb. w. Ramucirumab in Patients w. Gastric, Gastro-esophageal, or Esophageal Cancers
  • Official Title: A Phase 1b Study of Oraxol in Combination With Ramucirumab in Patients With Gastric, Gastro-esophageal, or Esophageal Cancers

Clinical Trial IDs

  • ORG STUDY ID: KX-ORAX-005
  • NCT ID: NCT02970539

Conditions

  • Gastric Cancer
  • Esophageal Cancer
  • Gastro-esophageal Cancer

Interventions

DrugSynonymsArms
OraxolOraxol +Ramucirumab
RamucirumabOraxol +Ramucirumab

Purpose

This is a nonrandomized, open-label, single group assignment, safety, tolerability and pharmacokinetic (PK) study to determine the MTD and optimal dosing regimen of Oraxol in combination with ramucirumab.

Detailed Description

      This is a sequential-group, dose escalation trial to determine the maximum tolerated dose of
      oral Oraxol in combination with intravenous ramucirumab. After a screening period of up to
      28 days subjects will be enrolled into the treatment phase of the study. Each cycle of
      therapy will last 4 weeks. Subjects may continue in the study until they experience disease
      progression or unacceptable toxicity. Three to six subjects will be enrolled at each dose
      level. Once the tolerability of a dose level has been determined, an additional 3-6 subjects
      may be enrolled at a higher dose level, to determine the maximum tolerated dose. Safety will
      be monitored through recording of adverse events, serious adverse events, monitoring of
      laboratory tests including hematology, blood chemistry, urinalyses, physical examinations
      and electrocardiograms. Subjects will undergo radiographic assessments for tumor response at
      specified time points. Blood samples will also be obtained in the first cycle of therapy at
      multiple time points for determination of the amount of paclitaxel and metabolites and
      HM30181 in the circulation. After the treatment period, there will be a follow-up period
      during which the subject or family may be contacted every three months for follow-up.
    

Trial Arms

NameTypeDescriptionInterventions
Oraxol +RamucirumabExperimental
  • Oraxol
  • Ramucirumab

Eligibility Criteria

        Inclusion Criteria:

          -  Subjects must meet all of the following criteria to be included in this study:

               1. Signed written informed consent

               2. ≥18 years of age

               3. Histologically or cytologically confirmed diagnosis of advanced stage gastric,
                  gastro-esophageal, or esophageal cancers in whom ramucirumab and paclitaxel are
                  reasonable treatments

               4. Have documented testing for human epidermal growth factor receptor 2 (HER2-neu)
                  overexpressing, and for those with tumors overexpressing HER2-neu, have
                  documented progression on Trastuzumab-containing therapy

               5. Measurable disease on computed tomography (CT) scan of thorax, abdomen, and
                  pelvis per RECIST v1.1 criteria

               6. Able to swallow oral medication as an intact dosage form

               7. Adequate hematologic status as demonstrated by not requiring transfusion support
                  or granulocyte-colony stimulating factor (G-CSF) to maintain: Absolute
                  neutrophil count (ANC) ≥1500 cells/mm3, Platelet count ≥100 x 109/L, Hemoglobin
                  ≥10 g/dL

               8. 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 (ALT) ≤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

               9. 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

              10. Normal prothrombin time (PT) or international normalized ratio (INR) and normal
                  activated partial thromboplastin time (aPTT)

              11. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1

              12. Life expectancy of at least 3 months

              13. 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

              14. 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:

          -  Subjects who meet any of the following criteria will be excluded from this study:

               1. Unresolved toxicity from previous anticancer treatments, including
                  investigational products (subjects must have recovered all unacceptable toxicity
                  to ≤ Grade 1 Common Terminology Criteria for Adverse Events [CTCAE] toxicity).
                  This does not extend to symptoms or findings that are attributable to the
                  underlying disease

               2. Received investigational products within 14 days or 5 half-lives of the first
                  study dosing day, whichever is longer

               3. Are currently receiving other medications or radiation intended for the
                  treatment of their malignancy

               4. Central nervous system metastases, including leptomeningeal involvement

               5. Women of childbearing potential who are pregnant or breastfeeding

               6. Currently taking a concomitant medication, other than a premedication, that is:

                    -  A known P-glycoprotein (P-gp) inhibitor or inducer. Subjects who are taking
                       such medications but who are otherwise eligible may be enrolled if they
                       discontinue the medication ≥1 week before dosing

                    -  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

                    -  Medications known to be clinically significant inhibitors (eg. gemfibrozil)
                       or inducers (eg. rifampin) of CYP2C8 or medications known to be strong
                       cytochrome P450 (CYP) 3A4 inhibitors (eg. ketoconazole) or inducers (eg.
                       rifampin or St. John's Wort). Subjects who are currently 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 during treatment with Oraxol.

               7. Require therapeutic use of anticoagulants other than daily aspirin or low
                  molecular weight heparin

               8. Require therapeutic use of nonsteroidal anti-inflammatory drugs (NSAIDs)

               9. Unable to receive iv contrast for required CT scans

              10. Systolic blood pressure >140mm Hg or diastolic blood pressure > 90 mm Hg

              11. Grade 3 gastrointestinal (GI) bleeding within 3 months prior to screening

              12. Arterial thromboembolic event including, but not limited to, myocardial
                  infarction, transient ischemic attack, or cerebrovascular accident within 6
                  months of enrollment

              13. Deep vein thrombosis (DVT) or pulmonary embolus which require use of oral
                  anticoagulants or, if on low molecular weight heparin, have not been on a stable
                  dose for at least 2 weeks

              14. Uncontrolled intercurrent illness including, but not limited to, ongoing or
                  active infection, symptomatic congestive heart failure, unstable angina
                  pectoris, cardiac arrhythmia, poorly controlled diabetes or diabetes with
                  established vascular complications, chronic pulmonary disease requiring oxygen,
                  known bleeding disorders, or any concomitant illness or social situation that
                  would limit compliance with study requirements

              15. Major surgery to the upper 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

              16. History of hypersensitivity to paclitaxel, not attributed to a hypersensitivity
                  type reaction to Cremophor®, or history of hypersensitivity type reaction to
                  polysorbate 80 or other components of the formulation of Oraxol

              17. History of developing any condition during prior treatment with ramucirumab for
                  which ramucirumab must be permanently discontinued according to the ramucirumab
                  label.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum tolerated dose (MTD) and dosing regimen of Oraxol as determined by dose limiting toxicity in patients with advanced stage gastric, gastro-esophageal, or esophageal cancers who are being treated with Oraxol in combination with ramucirumab
Time Frame:One month
Safety Issue:
Description:The MTD will be the highest dose at which no more than 1 of 6 subjects experience a dose-limiting toxicity (DLT) during treatment and Oraxol pharmacokinetics (PK) are acceptable.

Secondary Outcome Measures

Measure:Safety assessments of adverse event (AE) and serious adverse event (SAE) information of Oraxol in combination with ramucirumab
Time Frame:through study completion
Safety Issue:
Description:Safety assessments will consist of determining and recording all AEs (including for both increasing and decreasing severity) and SAEs
Measure:Laboratory evaluation for hematology, blood chemistry and urine analysis
Time Frame:through study completion
Safety Issue:
Description:
Measure:Periodic measurement of vital signs
Time Frame:From date of study start until the date of first documents progression or date of death from any cause, whichever came first, assessed up to 24 months
Safety Issue:
Description:
Measure:The recommended Phase 2 dose of Oraxol in combination with ramucirumab
Time Frame:One month
Safety Issue:
Description:
Measure:The amount of paclitaxel and its major metabolites in the blood stream
Time Frame:Day 1: Predose, 8 timepoints up to 8 hours postdose; Day 2: Predose; Day 3: Predose, 8 timepoints up to 8 hours postdose; Day 15: Predose, and between 1 and 3 hours postdose
Safety Issue:
Description:
Measure:The amount of HM30181A in the blood stream as determined by pharmacokinetic analysis
Time Frame:Day 1: Predose, 8 timepoints up to 8 hours postdose; Day 2: Predose; Day 3: Predose, 8 timepoints up to 8 hours postdose; Day 15: Predose, and between 1 and 3 hours postdose
Safety Issue:
Description:
Measure:Response rate
Time Frame:From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Safety Issue:
Description:
Measure:Progression-free survival
Time Frame:From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months.
Safety Issue:
Description:
Measure:Overall survival
Time Frame:From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years.
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Kinex Pharmaceuticals Inc

Last Updated

November 17, 2016