ClinicalTrials.gov
ClinicalTrials.gov Menu

Phase 1/2 Study of USL311 Alone and in Combination With Lomustine in Subjects With Advanced Solid Tumors and Relapsed/Recurrent Glioblastoma Multiforme (GBM)

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.
ClinicalTrials.gov Identifier: NCT02765165
Recruitment Status : Recruiting
First Posted : May 6, 2016
Last Update Posted : January 17, 2019
Sponsor:
Information provided by (Responsible Party):
Proximagen, LLC

Brief Summary:
This is a multicenter, open-label, Phase 1/2, dose-escalation and dose expansion study of a CXCR4 inhibitor, USL311, alone and in combination with lomustine in subjects with advanced solid tumors (Phase 1) and subjects with relapsed/recurrent GBM (Phase 2). The study is designed to explore the safety, tolerability, pharmacokinetics, and preliminary efficacy of USL311 alone and in combination with lomustine.

Condition or disease Intervention/treatment Phase
Solid Tumors (Phase 1) Relapsed/Recurrent GBM (Phase 2) Drug: USL311 Drug: Lomustine Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2 Dose-escalation of USL311 as Single Agent and in Combination With Lomustine (CCNU) in Subjects With Advanced Solid Tumors, With Subsequent Single Agent and Combination Phase 2 Cohorts for Subjects With Relapsed/Recurrent Glioblastoma Multiforme (GBM)
Actual Study Start Date : April 2016
Estimated Primary Completion Date : September 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Lomustine

Arm Intervention/treatment
Experimental: Dose-Escalation USL311, Solid Tumor, Part 1a
USL311, intravenous, once per week, starting at 60 mg/m˄2
Drug: USL311
Administered once weekly in a 21-day cycle

Experimental: Dose-Escalation USL311, Solid Tumor, Part 1b
USL311, oral, daily, starting at 40 mg
Drug: USL311
Administered once daily in a 21-day cycle

Experimental: Dose-Escalation USL311 with Lomustine, Solid Tumor, Part 2
USL311, oral, daily, starting at dose as determined in Part 1b, in combination with lomustine 90 mg/m˄2, oral, once every 6 weeks
Drug: USL311
Administered once daily in a 42-day cycle

Drug: Lomustine
Administered once every 6 weeks in a 42-day cycle

Experimental: Dose-Expansion, USL311, GBM, Part 3
USL311, oral, daily, starting at dose determined in Part 1b
Drug: USL311
Administered once daily in a 21-day cycle

Experimental: Dose-Expansion, USL311 with Lomustine, GBM, Part 4
USL311, oral, daily, in combination with lomustine, oral, once every 6 weeks, at dose(s) as determined in part 2
Drug: USL311
Administered once daily in a 42-day cycle

Drug: Lomustine
Administered once every 6 weeks in a 42-day cycle




Primary Outcome Measures :
  1. Phase 1: Maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) [ Time Frame: Approximately 26 weeks ]
    USL311 as a single agent in subjects with advanced solid tumors and USL311 in combination with lomustine in subjects with advanced solid tumors

  2. Phase 2: Percentage progression free survival (PFS) at 6 months (PFS-6m) [ Time Frame: Approximately 52 weeks ]
    USL311 as a single agent in subjects with relapsed/recurrent GBM and USL311 in combination with lomustine in subjects with relapsed/recurrent GBM


Secondary Outcome Measures :
  1. Phase 1 and Phase 2: Treatment-related adverse events as assessed by CTCAE v4.03 [ Time Frame: Approximately 26 or 52 weeks ]
    USL311 as a single agent and in combination with lomustine

  2. Phase 1 and Phase 2: Overall survival (OS) [ Time Frame: Approximately 26 or 52 weeks ]
    USL311 as a single agent and in combination with lomustine

  3. Phase 1 and Phase 2: Progression free survival (PFS) [ Time Frame: Approximately 26 or 52 weeks ]
    USL311 as a single agent and in combination with lomustine

  4. Phase 1 and Phase 2: Objective response rate (ORR%) [ Time Frame: Approximately 26 or 52 weeks ]
    USL311 as a single agent and in combination with lomustine

  5. Phase 1 and Phase 2: Peak concentration (Cmax) [ Time Frame: Approximately 26 or 52 weeks ]
    USL311 in plasma and whole blood and lomustine in plasma

  6. Phase 1 and Phase 2: Time to peak concentration (Tmax) [ Time Frame: Approximately 26 or 52 weeks ]
    USL311 in plasma and whole blood and lomustine in plasma

  7. Phase 1 and Phase 2: Area under the concentration vs time curve (AUC) [ Time Frame: Approximately 26 or 52 weeks ]
    USL311 in plasma and whole blood and lomustine in plasma



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, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

All Subjects:

  1. Provide signed and dated informed consent prior to study-specific screening procedures
  2. ≥ 18 years old
  3. Karnofsky performance status (KPS) ≥ 70
  4. Must have adequate bone marrow and renal/hepatic function within protocol specified limits
  5. Disease-free period of > 2 years from any other previous malignancies, excluding curatively treated basal cell carcinoma, squamous cell carcinoma of the skin, or carcinoma in situ of the cervix. Subjects with prostate cancer Stage 1 that do not require treatment may also be included
  6. Women and men must use protocol approved methods of contraception
  7. Must be able and willing to comply with the study visit schedule and study procedures
  8. Must be able to take oral medications
  9. Must have available archived tumor tissue and willing and able to provide consent for study access to such tissue
  10. For subjects with a history of seizures, must be adequately controlled on a stable regimen of anti-epileptic drugs

    For Phase 1 Subjects Only:

  11. Histologically or cytologically documented diagnosis of solid tumor for which no standard therapy is recognized or have failed or intolerant to the standard-of-care treatment
  12. Inoperable metastatic or locally advanced, unresectable disease
  13. Subjects may have either evaluable or measurable disease
  14. Subjects with treated (surgically excised or irradiated) and stable brain metastases are eligible as long as the subject has adequately recovered from treatment and the treatment was ≥ 28 days prior to initiation of study drug(s) and baseline brain computed tomography (CT) with contrast or magnetic resonance imaging (MRI) ≤ 14 days of initiation of study drug is negative for new brain metastases

    For Phase 2 Subjects Only:

  15. Histologically confirmed diagnosis of GBM
  16. Subjects must have documented recurrence after first-line treatment
  17. Prior first-line treatment must have included radiation and temozolomide
  18. Subject is suitable for re-resection, per Investigator discretion, as a component of their clinical care
  19. No more than one prior resection (Note: biopsy does not count as prior resection)

Exclusion Criteria:

All Subjects

  1. Subjects who have had recent systemic anticancer therapies, interventional device treatment and/or radiotherapy either within 14 days prior to first dose of study drug(s) or have not recovered (to grade ≤ 1) from all clinically significant toxicities related to prior therapies
  2. Subjects who have had any major surgery (not including re-resection surgery required in Phase 2) within 28 days prior to first dose of study drug(s), or minor surgery within 14 days prior to first day of study drug(s)
  3. Subjects taking any strong cytochrome P450 3A4 inducers within 14 days prior to the first dose of study drug(s)
  4. Subjects taking any strong cytochrome P450 3A4 inhibitors within 14 days prior to the first dose of study drug(s)
  5. Subjects taking any agents with moderate to high risk to prolong QTc interval or to cause Torsades de Pointes within 14 days prior to the first dose of study drug(s)
  6. Subjects who have been treated with an investigational agent or investigational interventional device within 21 days prior to the first dose of study drug(s)
  7. Subject is growth factor dependent or transfusion dependent, or has received growth factor support or transfusion support within 14 days prior to the first dose of study drug(s)
  8. History of significant cardiac disease
  9. Status epilepticus within 1 year prior to the first dose of study drug(s)
  10. Pregnant or breastfeeding
  11. Any other significant co-morbid conditions that in the opinion of the Investigator would impair study participation or cooperation

    For Phase 1 Subjects Only:

  12. Lymphoma as primary cancer

    For Phase 2 Subjects Only:

  13. Unable or unwilling to consent to the provision of resected tissue after surgery
  14. Prior treatment with plerixafor or another CXCR4 inhibitor
  15. Prior treatment with bevacizumab
  16. Prior treatment with lomustine and/or carmustine

    For All Cohorts Receiving Oral USL311:

  17. Any active medical condition or previous major abdominal surgery or procedure that might, in the investigator's opinion, have a significant effect on USL311 absorption

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): NCT02765165


Contacts
Contact: Shari Lennon 612-801-5550 slennon@proximagen.com
Contact: Tze-Chiang Meng, MD 952-658-7440 tcmeng@proximagen.com

Locations
United States, Missouri
Washington University Not yet recruiting
Saint Louis, Missouri, United States, 63110
Contact: Sarah Larson    314-747-1864      
United States, Oklahoma
University of Oklahoma Stephenson Cancer Center Active, not recruiting
Oklahoma City, Oklahoma, United States, 73104
United States, Texas
University of Texas/MD Anderson Cancer Center Terminated
Houston, Texas, United States, 77030
South Texas Accelerated Research Therapeutics (START) Recruiting
San Antonio, Texas, United States, 78229
Contact: Isabel Jimenez, RN, MSN    210-593-5265      
UT Health San Antonio Cancer Center Not yet recruiting
San Antonio, Texas, United States, 78229
Contact: Emily Cleveland, RN    210-450-5958      
Spain
South Texas Accelerated Research Therapeutics (START) - CIOCC Withdrawn
Madrid, Spain
South Texas Accelerated Research Therapeutics (START) - FJD Terminated
Madrid, Spain
Sponsors and Collaborators
Proximagen, LLC
Investigators
Study Director: Tze-Chiang Meng, MD Proximagen, LLC

Responsible Party: Proximagen, LLC
ClinicalTrials.gov Identifier: NCT02765165     History of Changes
Other Study ID Numbers: P311-201
First Posted: May 6, 2016    Key Record Dates
Last Update Posted: January 17, 2019
Last Verified: January 2019

Keywords provided by Proximagen, LLC:
Phase 1
Phase 2
Glioblastoma Multiforme
Glioblastoma
GBM
Brain Tumor
Brain Cancer
Tumor
Solid Tumor
Tumour
Lomustine
CCNU
CXCR4
Phase 1 Clinical Trial
Phase 2 Clinical Trial

Additional relevant MeSH terms:
Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Lomustine
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents