Clinical Trials /

Ulixertinib/Palbociclib in Patients With Advanced Pancreatic and Other Solid Tumors

NCT03454035

Description:

This phase I study is designed to establish the safety, maximally tolerated dose (MTD) and recommended phase II dose (RP2D) of the ERK inhibitor ulixertinib (BVD-523) when combined with the CDK4/6 inhibitor palbociclib.

Related Conditions:
  • Malignant Solid Tumor
  • Pancreatic Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Ulixertinib/Palbociclib in Patients With Advanced Pancreatic and Other Solid Tumors
  • Official Title: A Phase I Trial of Ulixertinib (BVD-523) in Combination With Palbociclib in Patients With Advanced Solid Tumors With Expansion Cohort in Previously Treated Metastatic Pancreatic Cancer

Clinical Trial IDs

  • ORG STUDY ID: LCCC1736
  • NCT ID: NCT03454035

Conditions

  • Tumor, Solid
  • Pancreatic Cancer

Interventions

DrugSynonymsArms
UlixertinibBVD-523Open-label, single arm Phase I
PalbociclibIbranceOpen-label, single arm Phase I

Purpose

This phase I study is designed to establish the safety, maximally tolerated dose (MTD) and recommended phase II dose (RP2D) of the ERK inhibitor ulixertinib (BVD-523) when combined with the CDK4/6 inhibitor palbociclib.

Detailed Description

      This phase I study is designed to establish the safety, maximally tolerated dose (MTD) and
      recommended phase II dose (RP2D) of the ERK inhibitor ulixertinib (BVD-523) when combined
      with the CDK4/6 inhibitor palbociclib.

      Up to a maximum of 30 adult patients will be enrolled in the 5 possible dose escalation
      cohorts. These patients will have histologically confirmed advanced solid tumor disease
      refractory to standard of care therapy, or for which there is no accepted standard of care.

      Finally, 15 adult patients will be treated at the recommended phase II dose (RP2D) in the
      expansion cohort involving metastatic pancreatic cancer patients who have received at least
      one line of therapy in the metastatic setting.
    

Trial Arms

NameTypeDescriptionInterventions
Open-label, single arm Phase IExperimentalUlixertinib added to palbociclib
  • Ulixertinib
  • Palbociclib

Eligibility Criteria

        Inclusion Criteria:

          1. Written informed consent and HIPAA authorization for release of personal health
             information. NOTE: HIPAA authorization may be included in the informed consent or
             obtained separately.

          2. Age ≥ 18 years at the time of consent (no upper age limit)

          3. Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2 (see Section 10.1
             Appendix A)

          4. Tumor Eligibility:

               1. Dose escalation cohorts: Histologically confirmed advanced solid tumor refractory
                  to standard of care therapy, or for which there is no accepted standard of care

               2. Expansion cohort (at RP2D): metastatic pancreatic cancer patients who have
                  received at least one line of therapy in the metastatic setting

          5. Measurable or non-measurable (but evaluable) disease according to RECIST v1.1 for dose
             escalating cohorts; measurable disease as per RECIST v1.1 required for expansion
             cohort

          6. Life expectancy ≥ 12 weeks

          7. Recovered from all reversible acute toxic effects of last anti-cancer treatment (other
             than alopecia) to ≤Grade 1 or baseline. Patients with baseline neuropathy that is ≤
             grade 2 are eligible for enrollment.

          8. Demonstrate adequate organ function as defined in the table below; all screening labs
             to be obtained within 28 days prior to day -6 of ulixertinib

        Hemoglobin (Hgb) ≥ 9 g/dL Absolute Neutrophil Count (ANC) ≥ 1,500 /mm3 Platelets ≥
        100,000/mm3 Creatinine ≤1.5 x upper limit of normal (ULN) or Calculated creatinine
        clearance ≥ 60 mL/min using the Cockcroft-Gault formula Bilirubin ≤ 1.5 x ULN Aspartate
        aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 2.5 x ULN; if tumor involvement
        of the liver ≤ 5 x ULN

          -  Note: Hematology and other lab parameters that are ≤ grade 2 but still meet criteria
             for study entry are allowed. Furthermore, changes in laboratory parameters during the
             study should not be considered adverse events unless they meet criteria for dose
             modification(s) of study medication outlined by the protocol and/or worsen from
             baseline during therapy.

             10. Adequate cardiac function; left ventricular ejection fraction (LVEF) >50% as
             assessed by ultrasound/echocardiography (ECHO); corrected QT interval (QTc) <470ms

             11. Females of childbearing potential must have a negative serum pregnancy test within
             3 days prior to day -6 of ulixertinib. NOTE: Females are considered of child bearing
             potential unless they are surgically sterile (have undergone a hysterectomy, bilateral
             tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at
             least 12 consecutive months

             12. Females of childbearing potential and males must be willing to abstain from
             heterosexual activity* or use effective methods of contraception from the time of
             informed consent until 120 days after treatment discontinuation. Acceptable
             contraception methods can be comprised of an intrauterine device (IUD), vasectomy of a
             female subject's male partner, contraceptive rod implanted into the skin, OR use of
             two of the following: diaphragm with spermicide (cannot be used in conjunction with
             cervical cap/spermicide), cervical cap with spermicide (nulliparous women only),
             contraceptive sponge (nulliparous women only), male condom or female condom (cannot be
             used together), hormonal contraceptive.] *Abstinence is acceptable if this is the
             usual lifestyle and preferred contraception for the subject.

             13. Subject is willing and able to comply with study procedures based on the judgement
             of the investigator or protocol designee.

             14. Willing to provide archival tissue (if available) and consent to mandatory
             pretreatment and on-treatment biopsy as deemed safe by the treating physician
             (expansion cohort only) for research purposes only.

        Exclusion Criteria:

          1. Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the
             mother is being treated on study)

          2. Treatment with any cancer-directed therapy (chemotherapy, hormonal therapy, biologic,
             radiation or immunotherapy, etc.) or investigational drug within 28 days or 5
             half-lives (whichever is shorter) prior to day -6 of ulixertinib

          3. A history or current evidence/risk of retinal vein occlusion (RVO) or central serous
             retinopathy (CSR).

          4. Major surgery within 28 days prior to day -6 of ulixertinib

          5. Not willing to avoid grapefruit, grapefruit juices, grapefruit hybrids, oranges,
             pummelos, and exotic citrus fruits from 7 days prior day -6 of ulixertinib and during
             the entire study due to potential CYP3A4 interaction with the study medications.

          6. Intake of any herbal preparations or medications (including, but not limited to, Saint
             John's Wort and ginkgo biloba) and dietary supplements within 7 days prior to day -6
             of ulixertinib due to potential CYP3A4 interaction with the study medications

          7. Unable or unwilling to discontinue use of any drug known to be a strong inhibitor of
             CYP3A4, CYP1A2 or CYP2D6 or strong inducer of CYP3A4 (prohibited inducers and
             inhibitors must be discontinued within 2 weeks prior to day -6 of ulixertinib; see
             section 10.3 Appendix C)

          8. Unable or unwilling to discontinue use of any drug known to be a sensitive CYP3A4
             substrate with a narrow therapeutic index; see section 10.3 Appendix C

          9. Known metastases of the central nervous system (CNS)

         10. Any important medical illness or abnormal laboratory finding that would increase the
             risk of participating in the study (based on the investigator's judgment)

         11. Psychiatric illness/social situations that would limit compliance with study
             requirements

         12. Has a known additional malignancy that is active and/or progressive requiring
             treatment; exceptions include basal cell or squamous cell skin cancer, in situ
             cervical or bladder cancer, or other cancer for which the patient has been disease
             free for at least five years

         13. Impaired GI function or GI disease that may significantly impair absorption (e.g.,
             inflammatory bowel disease (IBD), malabsorption syndrome, small bowel resection,
             uncontrolled vomiting or diarrhea)

         14. Inability to swallow oral medications
      
Maximum Eligible Age:99 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum Tolerated Dose (MTD)
Time Frame:Five weeks
Safety Issue:
Description:MTD of ulixertinib in combination with palbociclib in patients with advanced solid tumors of ulixertinib in combination with palbociclib in patients with advanced solid tumors

Secondary Outcome Measures

Measure:Safety (number of patients with adverse events)
Time Frame:5 weeks
Safety Issue:
Description:Number of patients with adverse events
Measure:Objective Response Rate
Time Frame:8 weeks
Safety Issue:
Description:To estimate objective response rate (ORR) after treatment with ulixertinib in combination with palbociclib
Measure:Progression-free survival
Time Frame:Up to two years after treatment
Safety Issue:
Description:To estimate progression-free survival (PFS) after treatment with ulixertinib in combination with palbociclib
Measure:Overall Survival
Time Frame:Up to two years after treatment
Safety Issue:
Description:For Expansion Cohort: To estimate overall survival (OS) after treatment with the recommended phase 2 dose of ulixertinib in combination with palbociclib in an expansion cohort of patients with metastatic pancreatic cancer
Measure:Cancer Antigen 19-9 (CA19-9) response
Time Frame:Through treatment completion, approximately 1 year
Safety Issue:
Description:For Expansion Cohort: To estimate CA19-9 response after treatment with ulixertinib in combination with palbociclib

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:UNC Lineberger Comprehensive Cancer Center

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