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

Sponsor
UNC Lineberger Comprehensive Cancer Center (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT03454035
Collaborator
BioMed Valley Discoveries, Inc (Industry), Pfizer (Industry)
45
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68.8
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Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
Phase 1

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
45 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Intervention Model Description:
This is a standard 3+3 dose escalation design.This is a standard 3+3 dose escalation design.
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Jan 30, 2018
Anticipated Primary Completion Date :
Oct 24, 2022
Anticipated Study Completion Date :
Oct 24, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: Open-label, single arm Phase I

Ulixertinib added to palbociclib

Drug: Ulixertinib
Ulixertinib 300mg, orally, twice a day concomitantly with palbociclib
Other Names:
  • BVD-523
  • Drug: Palbociclib
    Drug: Palbociclib 125mg, orally, once a day concomitantly with ulixertinib
    Other Names:
  • Ibrance
  • Outcome Measures

    Primary Outcome Measures

    1. Maximum Tolerated Dose (MTD) [Five weeks]

      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

    2. Overall Survival [6 months after treatment]

      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

    Secondary Outcome Measures

    1. Safety (number of patients with adverse events) [5 weeks]

      Number of patients with adverse events

    2. Objective Response Rate [8 weeks]

      To estimate objective response rate (ORR) after treatment with ulixertinib in combination with palbociclib

    3. Progression-free survival [Up to two years after treatment]

      To estimate progression-free survival (PFS) after treatment with ulixertinib in combination with palbociclib

    4. Overall Survival [Up to two years after treatment]

      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

    5. Cancer Antigen 19-9 (CA19-9) response [Through treatment completion, approximately 1 year]

      For Expansion Cohort: To estimate CA19-9 response after treatment with ulixertinib in combination with palbociclib

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 99 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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:

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

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

    7. 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

    8. Life expectancy ≥ 12 weeks

    9. 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.

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

    2. 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

    3. 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.

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

    5. 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Lineberger Comprehensive Cancer Center Chapel Hill North Carolina United States 27599

    Sponsors and Collaborators

    • UNC Lineberger Comprehensive Cancer Center
    • BioMed Valley Discoveries, Inc
    • Pfizer

    Investigators

    • Principal Investigator: Autumn McRee, MD, University of North Carolina, Chapel Hill

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    UNC Lineberger Comprehensive Cancer Center
    ClinicalTrials.gov Identifier:
    NCT03454035
    Other Study ID Numbers:
    • LCCC1736
    First Posted:
    Mar 5, 2018
    Last Update Posted:
    Aug 11, 2022
    Last Verified:
    Aug 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Aug 11, 2022