Clinical Trials /

Study of Oraxol and Pembrolizumab in Subjects With Advanced Solid Tumors

NCT03588039

Description:

This is an open-label, Phase 1 dose-escalation study followed by a 3-arm expansion cohort of Oraxol administered in combination with pembrolizumab.

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Esophageal Adenocarcinoma
  • Gastric Adenocarcinoma
  • Malignant Solid Tumor
  • Non-Small Cell Lung Carcinoma
  • Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of Oraxol and Pembrolizumab in Subjects With Advanced Solid Tumors
  • Official Title: Phase 1 Study With Expansion Cohorts to Assess the Safety, Tolerability, and Activity of Oraxol (Paclitaxel + HM30181A) in Combination With Pembrolizumab in Subjects With Advanced Solid Malignancies

Clinical Trial IDs

  • ORG STUDY ID: KX-ORAX-011
  • NCT ID: NCT03588039

Conditions

  • Solid Tumor

Interventions

DrugSynonymsArms
Oraxoloral HM30181A + oral paclitaxelDose escalation-Arm 1
PembrolizumabKeytrudaDose escalation-Arm 1

Purpose

This is an open-label, Phase 1 dose-escalation study followed by a 3-arm expansion cohort of Oraxol administered in combination with pembrolizumab.

Detailed Description

      This is a two part study. The dose escalation part will enroll subjects with advanced solid
      tumors for which pembrolizumab is an FDA-approved therapy, to determine the MTD and identify
      the recommended phase 2 dose of paclitaxel administered as Oraxol in combination with
      pembrolizumab. Upon determination of the phase 2 dose, the dose expansion part will enroll
      subjects with advanced/metastatic urothelial, gastric/gastro-esophageal, or NSCLC into 3
      independent cohorts/arms to further evaluate the activity and safety of the study treatment.
    

Trial Arms

NameTypeDescriptionInterventions
Dose escalation-Arm 1ExperimentalDuring the dose escalation period Oraxol will be administered once daily for 2 days per week for 2 weeks followed by 1 week off treatment (2 weeks on and 1 week off). Pembrolizumab will be administered on Day 1 of each 3-week cycle.
  • Oraxol
  • Pembrolizumab
Dose escalation-Arm 2ExperimentalDuring the dose escalation period Oraxol will be administered once daily for 3 days per week for 2 weeks followed by 1 week off treatment (2 weeks on and 1 week off). Pembrolizumab will be administered on Day 1 of each 3-week cycle.
  • Oraxol
  • Pembrolizumab
Dose escalation-Arm 3ExperimentalDuring the dose escalation period Oraxol will be administered once daily for 4 days per week for 2 weeks followed by 1 week off treatment (2 weeks on and 1 week off). Pembrolizumab will be administered on Day 1 of each 3-week cycle.
  • Oraxol
  • Pembrolizumab
Dose escalation-Arm 4ExperimentalDuring the dose escalation period Oraxol will be administered once daily for 5 days per week for 2 weeks followed by 1 week off treatment (2 weeks on and 1 week off). Pembrolizumab will be administered on Day 1 of each 3-week cycle.
  • Oraxol
  • Pembrolizumab
Dose escalation-Arm 5ExperimentalDuring the dose escalation period Oraxol will be administered once daily for 5 days per week for 2 weeks followed by 1 week off treatment (2 weeks on and 1 week off). Pembrolizumab will be administered on Day 1 of each 3-week cycle.
  • Oraxol
  • Pembrolizumab
Dose escalation-Arm 6ExperimentalDuring the dose escalation period Oraxol will be administered once daily for 5 days per week for 2 weeks followed by 1 week off treatment (2 weeks on and 1 week off). Pembrolizumab will be administered on Day 1 of each 3-week cycle.
  • Oraxol
  • Pembrolizumab
Dose expansion-Gastric/GEExperimentalThe dose expansion period will enroll subjects with gastric/gastro-esophageal cancer to further evaluate the activity and safety of the study treatment. Oraxol will be administered at the dose determined from part 1 for 2 out of 3 weeks. Pembrolizumab will be administered on Day 1 of each 3-week cycle.
  • Oraxol
  • Pembrolizumab
Dose expansion-NSCLC cancerExperimentalThe dose expansion period will enroll subjects with NSCLC to further evaluate the activity and safety of the study treatment. Oraxol will be administered at the dose determined from part 1 for 2 out of 3 weeks. Pembrolizumab will be administered on Day 1 of each 3-week cycle.
  • Oraxol
  • Pembrolizumab
Dose expansion-Urothelial cancerExperimentalThe dose expansion period will enroll subjects with advanced/metastatic urothelial to further evaluate the activity and safety of the study treatment. Oraxol will be administered at the dose determined from part 1 for 2 out of 3 weeks. Pembrolizumab will be administered on Day 1 of each 3-week cycle.
  • Oraxol
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  Able to understand and sign an informed consent form

          -  Age ≥18 years

          -  Dose Escalation: Histologically confirmed metastatic or unresectable solid tumors for
             which pembrolizumab is an FDA-approved therapy

          -  Dose Expansion: Histologically confirmed diagnosis of advanced or metastatic
             urothelial carcinoma, gastric/gastro-esophageal adenocarcinoma or NSCLC. NSCLC
             patients with EGFR or ALK translocation must have previously progressed on
             FDA-approved therapy for these aberrations (accounting for PD-1 expression in each
             histologic subtype)

          -  Dose Expansion: Must have stable disease or progressed on previously failed anti-PD1
             or anti-PD-L1 therapy

          -  Previously progressed on or become intolerant of at least 1 line of systemic
             chemotherapy for metastatic or advanced disease

          -  Must have at least one measurable site of disease as defined as per RECIST v1.1
             criteria

          -  ECOG Performance Status ≤1

          -  Must have adequate hematology, blood chemistry, liver function and renal function.

          -  Willing and able to comply with scheduled visits, treatment plan and laboratory tests

          -  No concurrent malignancy except curatively treated basal or squamous cell carcinoma of
             the skin or carcinoma in situ of the cervix, breast, or bladder

          -  Subjects 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.

          -  Men who are sterile (including vasectomy confirmed by post vasectomy semen analysis)
             OR agree to use a condom with spermicide and to not donate sperm during the study and
             for at least 30 days following last dose of Oraxol

          -  Female subjects 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 assigned study treatment. Abstinence is also an acceptable form of
             contraception.

          -  Subjects who are of childbearing potential must have a negative serum pregnancy test
             at Screening and within 96 hours before Week 1 dosing.

          -  Willing to return for follow-up

          -  Willing to provide blood samples for correlative research purposes

          -  Life expectancy of at least 3 months

        Exclusion Criteria:

          -  Subjects with history of prior treatment with taxanes (eg, paclitaxel, docetaxel,
             cabazitaxel) in expansion cohorts only

          -  History of prior significant toxicity from anti-PD-1 or anti-PDL1 therapy requiring
             discontinuation of treatment

          -  Subjects who have not recovered from recent anti-cancer therapy received.

          -  Current or prior use of immunosuppressive medication within 14 days before the first
             dose of pembrolizumab.

          -  Vaccinated with live, attenuated vaccines within 28 days of the first dose of the
             study drug

          -  Active or prior documented autoimmune or inflammatory disorders. The following are
             exceptions to this criterion:

               -  Subjects with vitiligo or alopecia

               -  Subjects with hypothyroidism (eg, following Hashimoto's thyroiditis) stable on
                  hormone replacement therapy or psoriasis not requiring systemic treatment

          -  Subject has impairment of GI function or GI disease that may significantly alter the
             absorption of study drugs (including gastric bypass surgery and total gastrectomy).
             Subjects with partial gastrectomy may be included in the trial.

          -  Uncontrolled concurrent illness.

          -  Known or suspected diagnosis of human immunodeficiency virus (HIV) or chronic active
             Hepatitis B or C, or cirrhosis.

          -  Clinically significant pulmonary illness resulting in Grade ≥2 hypoxia.

          -  Symptomatic or uncontrolled brain metastases requiring current treatment (less than 28
             days from last cranial radiation or 28 days from last steroids use).

          -  Impaired cardiac function or clinically significant cardiac disease.

          -  Subjects with a healing or open wound

          -  Lack of recovery of prior AEs to Grade ≤1 severity (NCI CTCAE v4.03) (except alopecia)
             due to medications administered prior to the first dose of the trial drugs.

          -  Any other condition or finding (including social situation) that in the opinion of the
             Investigator may render the patient at excessive risk for treatment complications or
             may not be able provide evaluable outcome information.

          -  Pregnant or breast-feeding women

          -  Known allergy to any of the formulation components of Oraxol (oral paclitaxel or
             HM30181A) or
      
Maximum Eligible Age:99 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Determination of MTD
Time Frame:3 weeks
Safety Issue:
Description:dose limiting toxicities occuring in the first cycle of therapy

Secondary Outcome Measures

Measure:Progression free survival (PFS)
Time Frame:24 months
Safety Issue:
Description:To determine the progression free survival after initiation of treatment with Oraxol in subjects
Measure:Overall survival (OS)
Time Frame:24 months
Safety Issue:
Description:To determine the overall survival after initiation of treatment with Oraxol in subjects
Measure:duration of response (DOS)
Time Frame:24 months
Safety Issue:
Description:The duration of response will be measured in subjects associated with Oraxol administered in combination with pembrolizumab in subjects with advanced/metastatic urothelial, gastric/gastro-esophageal, or NSCLC who have stable disease or progressed on previous anti-PD1 or anti-PDL1 therapy
Measure:Pharmacokinetics of Oraxol
Time Frame:Day 1 and day 2
Safety Issue:
Description:Plasma concentrations of Oraxol

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Athenex, Inc.

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