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

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ClinicalTrials.gov Identifier: NCT03454035
Recruitment Status : Recruiting
First Posted : March 5, 2018
Last Update Posted : April 14, 2021
Sponsor:
Collaborators:
BioMed Valley Discoveries, Inc
Pfizer
Information provided by (Responsible Party):
UNC Lineberger Comprehensive Cancer Center

Tracking Information
First Submitted Date  ICMJE February 5, 2018
First Posted Date  ICMJE March 5, 2018
Last Update Posted Date April 14, 2021
Actual Study Start Date  ICMJE January 30, 2018
Estimated Primary Completion Date October 24, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 26, 2018)
  • Maximum Tolerated Dose (MTD) [ Time Frame: 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
  • Overall Survival [ Time Frame: 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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 26, 2018)
  • Safety (number of patients with adverse events) [ Time Frame: 5 weeks ]
    Number of patients with adverse events
  • Objective Response Rate [ Time Frame: 8 weeks ]
    To estimate objective response rate (ORR) after treatment with ulixertinib in combination with palbociclib
  • Progression-free survival [ Time Frame: Up to two years after treatment ]
    To estimate progression-free survival (PFS) after treatment with ulixertinib in combination with palbociclib
  • Overall Survival [ Time Frame: 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
  • Cancer Antigen 19-9 (CA19-9) response [ Time Frame: Through treatment completion, approximately 1 year ]
    For Expansion Cohort: To estimate CA19-9 response after treatment with ulixertinib in combination with palbociclib
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Ulixertinib/Palbociclib in Patients With Advanced Pancreatic and Other Solid Tumors
Official Title  ICMJE 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
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.
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:
This is a standard 3+3 dose escalation design.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Tumor, Solid
  • Pancreatic Cancer
Intervention  ICMJE
  • Drug: Ulixertinib
    Ulixertinib 300mg, orally, twice a day concomitantly with palbociclib
    Other Name: BVD-523
  • Drug: Palbociclib
    Drug: Palbociclib 125mg, orally, once a day concomitantly with ulixertinib
    Other Name: Ibrance
Study Arms  ICMJE Experimental: Open-label, single arm Phase I
Ulixertinib added to palbociclib
Interventions:
  • Drug: Ulixertinib
  • Drug: Palbociclib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 9, 2021)
45
Original Estimated Enrollment  ICMJE
 (submitted: February 26, 2018)
30
Estimated Study Completion Date  ICMJE October 24, 2023
Estimated Primary Completion Date October 24, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 99 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Brian Burgess 919-966-4432 brian_burgess@med.unc.edu
Contact: Catherine Griffin 919-966-4432 catherine_griffin@med.unc.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03454035
Other Study ID Numbers  ICMJE LCCC1736
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party UNC Lineberger Comprehensive Cancer Center
Study Sponsor  ICMJE UNC Lineberger Comprehensive Cancer Center
Collaborators  ICMJE
  • BioMed Valley Discoveries, Inc
  • Pfizer
Investigators  ICMJE
Principal Investigator: Autumn McRee, MD University of North Carolina, Chapel Hill
PRS Account UNC Lineberger Comprehensive Cancer Center
Verification Date April 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP