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

NCT02970539 | Unknown Phase 1 FDA Drug

• 1 other identifier: KX-ORAX-005
• Study Type: interventional
• Target: 36
• Locations: 2 countries
• Sites: 5

Brief Summary

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.

Conditions

Gastric Cancer; Esophageal Cancer; Gastro-esophageal Cancer

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose (MTD)

  The primary endpoint of determining the MTD will be based on DLT

  The first 4 weeks

Secondary Outcomes (13)

• To determine the safety and tolerability of Oraxol in combination with ramucirumab

  through study completion

• The recommended Phase 2 dose of Oraxol in combination with ramucirumab

  One month

• To characterize the area under the blood concentration curve (AUCt) of Oraxol in combination with ramucirumab

  Day 1 and 3: Predose, 8 timepoints up to 8 hours postdose; Day 2: Predose; Day 8 and 15: Predose, and between 1 and 3 hours postdose

• To characterize the area under the plasma concentration-time curve from 0 to 8 hours (AUC0-8h) of Oraxol in combination with ramucirumab

  Day 1 and 3: Predose, 8 timepoints up to 8 hours postdose; Day 2: Predose; Day 8 and 15: Predose, and between 1 and 3 hours postdose

• To characterize the maximum observed plasma concentration (Cmax) of Oraxol in combination with ramucirumab

  Day 1 and 3: Predose, 8 timepoints up to 8 hours postdose; Day 2: Predose; Day 8 and 15: Predose, and between 1 and 3 hours postdose

Study Arms (1)

Oraxol +Ramucirumab

EXPERIMENTAL

Oraxol (oral HM30181 + oral paclitaxel) * HM30181 methanesulfonate monohydrate - supplied as 15-mg HM30181AK-US tablets * Paclitaxel - supplied as 30-mg capsules Ramucirumab - supplied as a solution at a concentration of 10 mg/mL

Drug: Oraxol; Drug: Ramucirumab

Interventions

Oraxol DRUG

Oraxol (Paclitaxel and HM30181A) will be dosed orally. Paclitaxel will be supplied as capsules and HM30181A will be supplied as tablets.

Also known as: oral HM30181AK-US tablet and paclitaxel capsule

Oraxol +Ramucirumab

Ramucirumab DRUG

Ramucirumab will be administered by iv infusion and supplied as a solution at a concentration of 10 mg/mL

Also known as: LY3009806

Oraxol +Ramucirumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must meet all of the following criteria to be included in this study:
• \. Signed written informed consent 2. ≥18 years of age 3. Histologically or cytologically confirmed diagnosis of advanced stage gastric, gastro-esophageal (Part 1 or Part 2), or esophageal adenocarcinoma (Part 1 only) with disease progression on or after prior fluoropyrimidine- or platinum-containing chemotherapy 4. Have documented testing for HER2-neu overexpression, 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:
• ANC ≥1500 cells/mm3
• Platelet count ≥100 x 109/L
• Hemoglobin ≥10 g/dL; subjects with thalassemia having a hemoglobin \<10 g/dL may be enrolled, per Investigator discretion 8. Adequate liver function as demonstrated by:
• Total bilirubin of ≤1.5 mg/dL
• 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
• Gamma-glutamyl transferase (GGT) \<10 x ULN 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
• Urinary protein ≤1+. If urinary protein is ≥2+, a 24-hour urine collection for protein must demonstrate \<1000 mg of protein in 24 hours to allow participation in this protocol.
• \. Normal prothrombin time (PT) or international normalized ratio (INR) and normal activated partial thromboplastin time (aPTT) unless subject is on anticoagulation therapy 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.
• \. 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.

You may not qualify if:

• Subjects who meet any of the following criteria will be excluded from this study:
• 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.
• Received investigational products within 14 days or 5 half-lives of the first study dosing day, whichever is longer; subjects receiving biologic agents (eg, monoclonal antibodies) require a 30-day washout period.
• Are currently receiving other medications or radiation intended for the treatment of their malignancy
• Central nervous system metastases, including leptomeningeal involvement
• Women of childbearing potential who are pregnant or breastfeeding
• Currently taking a concomitant medication, other than a premedication, that is:
• A strong 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 strong inhibitors (gemfibrozil) or inducers (rifampin) of cytochrome P450 (CYP) 2C8 or medications known to be strong CYP3A4 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.
• Use of warfarin. Participants receiving warfarin who are otherwise eligible and who may be appropriately managed with low molecular weight heparin, in the opinion of the Investigator, may be enrolled in the study provided they are switched to low molecular weight heparin at least 7 days prior to receiving study treatment.
• Require chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs), chronic antiplatelet therapy, dipyridamole, clopidogrel, or similar agents. Aspirin up to 325 mg per day is allowed.
• Unable to receive iv contrast for required CT scans
• Poorly-controlled hypertension (\>160 mm Hg systolic or \>100 mm Hg diastolic for \>4 weeks) despite standard medical management. Subjects may be rescreened after adjustment of their antihypertensive medication.
• Serious or nonhealing wound, ulcer, or bone fracture within 28 days prior to first dose of protocol therapy

Sponsors & Collaborators

• Athenex, Inc.: lead

Study Sites (5)

CTRC-UT

San Antonio, Texas, 78229, United States

Location

China Medical University Hospital

Taichung, Taiwan

Location

Tri-Service General Hospital

Taipei, 11490, Taiwan

Location

Taipei Veterans General Hospital

Taipei, Taiwan

Location

Lotung Poh-Ai Hospital

Yilan, 26546, Taiwan

Location

MeSH Terms

Conditions

Stomach Neoplasms; Esophageal Neoplasms

Interventions

Paclitaxel; Ramucirumab

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Head and Neck Neoplasms; Esophageal Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• David Cutler, MD

  Athenex, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Part 1 of the study will follow the standard "3+3" study design to determine the MTD of Oraxol administered continuously for 3 consecutive days per week (3-day MTD) in combination with ramucirumab. And Part 2 will obtain confirmatory activity, safety, and tolerability data.

Study Record Dates

• First Submitted: November 3, 2016
• First Posted: November 22, 2016
• Study Start: December 8, 2016
• Primary Completion: March 27, 2019
• Study Completion: December 31, 2022
• Last Updated: February 16, 2022

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share

Locations

TW (4); US (1)