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A Study of PLX2853 in Advanced Malignancies.

This study is currently recruiting participants.
Verified October 2017 by Plexxikon
Sponsor:
ClinicalTrials.gov Identifier:
NCT03297424
First Posted: September 29, 2017
Last Update Posted: October 26, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Plexxikon
  Purpose
The purpose of this research study is to evaluate safety, pharmacokinetics, pharmacodynamics and preliminary efficacy of the investigational drug PLX2853 in subjects with advanced malignancies.

Condition Intervention Phase
Small Cell Lung Cancer Uveal Melanoma Ovarian Clear Cell Carcinoma Non-Hodgkin Lymphoma Advanced Malignancies Solid Tumor Diffuse Large B Cell Lymphoma Follicular Lymphoma Drug: PLX2853 Phase 1 Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b/2a Dose-escalation Study to Assess Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of PLX2853 in Subjects With Advanced Malignancies

Resource links provided by NLM:


Further study details as provided by Plexxikon:

Primary Outcome Measures:
  • Number of participants with treatment-related adverse events as assessed by CTCAE v4.03. [ Time Frame: First dose of study drug through at least 30 days after end of treatment. ]
  • Area under the concentration-time curve (AUC) of PLX2853. [ Time Frame: From first dose of PLX2853 up to 30 days after end of treatment. ]
  • Maximum observed concentration (Cmax) of PLX2853. [ Time Frame: From first dose of PLX2853 up to 30 days after end of treatment. ]
  • Time to peak concentration (Tmax) of PLX2853. [ Time Frame: From first dose of PLX2853 up to 30 days after end of treatment. ]
  • Half life (t1/2) of PLX2853. [ Time Frame: From first dose of PLX2853 up to 30 days after end of treatment. ]
  • Number of participants who experience dose limiting toxicity as defined in the protocol. [ Time Frame: Up to 2 years ]
    The highest dose level at which less than 2 of 6 participants or less than 33% of participants (if cohort is expanded beyond 6) experience a dose limiting toxicity will be considered the maximum tolerated dose / recommended phase 2 dose.

  • Change in disease burden using RECIST 1.1 (solid tumors) or Lugano criteria (NHL). [ Time Frame: Up to 2 years ]

Secondary Outcome Measures:
  • Overall response rate (ORR) defined according to standard criteria for the relevant malignancy [Phase1b] [ Time Frame: From the first dose of study drug until the date of documented response to treatment, assessed up to 2 years. ]
  • Duration of response (DOR) [ Time Frame: DOR defined as the time from the initial objective response to disease progression or death, whichever occurs first, assessed up to 2 years. ]
  • Progression-Free Survival (PFS) [ Time Frame: PFS time is defined as the time from the first dose of PLX2853 to disease progression or death, whichever occurs first, assessed up to 2 years. ]
  • Overall Survival (OS) [ Time Frame: From the first dose of study drug until the date of death from any cause, assessed up to 2 years. ]

Estimated Enrollment: 166
Actual Study Start Date: September 12, 2017
Estimated Study Completion Date: May 2021
Estimated Primary Completion Date: December 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: PLX2853

Phase 1b (Dose Escalation): Up to 30 Subjects with advanced malignancies.

Phase 2a (Dose Expansion): There will be 5 total expansion cohorts. Either 10 or 29 subjects per cohort in each of 4 expansion cohorts: advanced SCLC, uveal melanoma, OCCC, and any other advanced malignancy with a known ARID1A mutation (between 40 to 116 subjects total for the solid tumor expansion phase). For the 5th expansion cohort, up to 20 subjects may be enrolled for NHL.

Drug: PLX2853
tablets
Other Name: PLX2853 tablets

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Confirmed diagnosis of one of the following, and must be measurable or evaluable per RECIST 1.1 (solid tumors) or Lugano (NHL):
  • Phase 1b:

    • Histologically confirmed advanced refractory solid tumor that is measurable or evaluable per RECIST 1.1 criteria.
    • Histologically confirmed NHL: diffuse large B-cell lymphoma and follicular lymphoma (Grade 1-3A) that has progressed following at least 1 line of prior anticancer therapy.
  • Phase 2a: Patients with various solid tumors or NHL who have received prior therapy.
  • Age ≥18 years
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
  • Life expectancy ≥3 months in the judgement of the investigator
  • Adequate organ function as appropriate for the disease under study. All screening laboratory tests should be performed within 10 days of treatment initiation.
  • Women of child-bearing potential (WOCBP) must have a negative serum pregnancy test at Screening (≤7 days prior to 1st study drug dose) and must agree to use an effective form of contraception from the time of the negative pregnancy test up to 6 months after the last dose of study drug. Effective forms of contraception include abstinence, hormonal contraceptive in conjunction with a barrier method, or a double barrier method. Women of non-child-bearing potential may be included if they are either surgically sterile or have been postmenopausal for ≥1 year.
  • Fertile men must agree to use an effective method of birth control during the study and for up to 6 months after the last dose of study drug.
  • All associated clinically significant drug-related toxicity from previous cancer therapy must be resolved prior to study treatment administration (alopecia is allowed).
  • Willingness and ability to provide written informed consent prior to any study-related procedures and to comply with all study requirements

Exclusion Criteria:

  • Prior exposure to a bromodomain inhibitor, such as OTX-015 or CPI-0610
  • Known uncontrolled fungal, bacterial, and/or viral infection ≥Grade 2
  • Uncontrolled autoimmune hemolytic anemia or thrombocytopenia
  • Presence of symptomatic or uncontrolled central nervous system or leptomeningeal metastases
  • Known or suspected allergy to the investigational agent or any agent given in association with this trial
  • Clinically significant cardiac arrhythmias including bradyarrhythmias and/or subjects who require anti-arrhythmic therapy (excluding beta blockers or digoxin). Subjects with controlled atrial fibrillation are not excluded.
  • Inability to take oral medication or significant nausea and vomiting, malabsorption, or significant small bowel resection that, in the opinion of the Investigator, would preclude adequate absorption
  • Non-healing wound, ulcer, or bone fracture
  • Subject has known human immunodeficiency virus (HIV), hepatitis B or hepatitis C infection or is known to be a carrier of hepatitis B or C.
  • History (within 2 years prior to first study drug administration) of another malignancy unless the malignancy was treated with curative intent and likelihood of relapse is small. Subjects with a history of squamous or basal cell carcinoma of the skin or carcinoma in situ of the cervix may be enrolled.
  • Persistent, unresolved ≥Grade 2 clinically significant drug-related toxicity (except alopecia, erectile impotence, hot flashes, libido, neuropathy) associated with previous treatment
  • Major surgery or significant traumatic injury within 14 days prior to Cycle 1 Day 1
  • Receipt of anti-cancer therapy prior to Cycle 1 Day 1: no chemotherapy, radiation therapy, small molecule tyrosine kinase inhibitor (TKI), or hormonal therapy for the treatment of cancer within 14 days or 5 half-lives (whichever is shorter) of Cycle 1 Day 1. No immune therapy or other biologic therapy (other monoclonal antibodies or antibody-drug conjugates [ADCs]) for the treatment of cancer within 28 days of Cycle 1 Day 1.
  • Subject is receiving systemic steroids at doses greater than the equivalent of prednisone 10 mg daily, with the exception of intermittent use for the treatment of emesis
  • Subject is participating in any other therapeutic clinical study (observational or registry trials are allowed)
  • Female subjects who are pregnant or breast-feeding
  • Presence of any other medical, psychological, familial, sociological, or geographic condition potentially hampering compliance with the study protocol or would interfere with the study endpoints or the subject's ability to participate in the study in the judgement of the investigator
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03297424


Contacts
Contact: Michael Pelayo 510-647-4038 MPelayo@plexxikon.com

Locations
United States, Arizona
Honor Health Recruiting
Scottsdale, Arizona, United States, 85258
Sponsors and Collaborators
Plexxikon
  More Information

Responsible Party: Plexxikon
ClinicalTrials.gov Identifier: NCT03297424     History of Changes
Other Study ID Numbers: PLX124-01
First Submitted: September 8, 2017
First Posted: September 29, 2017
Last Update Posted: October 26, 2017
Last Verified: October 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Plexxikon:
PLX2853
Small cell lung cancer (SCLC)
Uveal Melanoma
Ovarian Clear Cell Carcinoma
Non-Hodgkin Lymphoma
Advanced Malignancies
Solid Tumor
Diffuse Large B Cell Lymphoma (DLBCL)
Follicular Lymphoma (FL)
ARID1A

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Melanoma
Neoplasms
Small Cell Lung Carcinoma
Adenomyoepithelioma
Adenocarcinoma, Clear Cell
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Nevi and Melanomas
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Neoplasms, Complex and Mixed
Adenocarcinoma