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

NCT02765165

Description:

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.

Related Conditions:
  • Glioblastoma
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: P311-201
  • NCT ID: NCT02765165

Conditions

  • Solid Tumors (Phase 1)
  • Relapsed/Recurrent GBM (Phase 2)

Interventions

DrugSynonymsArms
USL311Dose-Escalation USL311, Solid Tumor, Part 1a
USL311Dose-Escalation USL311, Solid Tumor, Part 1b
USL311Dose-Escalation USL311 with Lomustine, Solid Tumor, Part 2
LomustineDose-Escalation USL311 with Lomustine, Solid Tumor, Part 2

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Dose-Escalation USL311, Solid Tumor, Part 1aExperimentalUSL311, intravenous, once per week, starting at 60 mg/m˄2
  • USL311
Dose-Escalation USL311, Solid Tumor, Part 1bExperimentalUSL311, oral, daily, starting at 40 mg
  • USL311
Dose-Escalation USL311 with Lomustine, Solid Tumor, Part 2ExperimentalUSL311, oral, daily, starting at dose as determined in Part 1b, in combination with lomustine 90 mg/m˄2, oral, once every 6 weeks
  • USL311
  • Lomustine
Dose-Expansion, USL311, GBM, Part 3ExperimentalUSL311, oral, daily, starting at dose determined in Part 1b
  • USL311
Dose-Expansion, USL311 with Lomustine, GBM, Part 4ExperimentalUSL311, oral, daily, in combination with lomustine, oral, once every 6 weeks, at dose(s) as determined in part 2
  • USL311
  • Lomustine

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase 1: Maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D)
Time Frame:Approximately 26 weeks
Safety Issue:
Description:USL311 as a single agent in subjects with advanced solid tumors and USL311 in combination with lomustine in subjects with advanced solid tumors

Secondary Outcome Measures

Measure:Phase 1 and Phase 2: Treatment-related adverse events as assessed by CTCAE v4.03
Time Frame:Approximately 26 or 52 weeks
Safety Issue:
Description:USL311 as a single agent and in combination with lomustine
Measure:Phase 1 and Phase 2: Overall survival (OS)
Time Frame:Approximately 26 or 52 weeks
Safety Issue:
Description:USL311 as a single agent and in combination with lomustine
Measure:Phase 1 and Phase 2: Progression free survival (PFS)
Time Frame:Approximately 26 or 52 weeks
Safety Issue:
Description:USL311 as a single agent and in combination with lomustine
Measure:Phase 1 and Phase 2: Objective response rate (ORR%)
Time Frame:Approximately 26 or 52 weeks
Safety Issue:
Description:USL311 as a single agent and in combination with lomustine
Measure:Phase 1 and Phase 2: Peak concentration (Cmax)
Time Frame:Approximately 26 or 52 weeks
Safety Issue:
Description:USL311 in plasma and whole blood and lomustine in plasma
Measure:Phase 1 and Phase 2: Time to peak concentration (Tmax)
Time Frame:Approximately 26 or 52 weeks
Safety Issue:
Description:USL311 in plasma and whole blood and lomustine in plasma
Measure:Phase 1 and Phase 2: Area under the concentration vs time curve (AUC)
Time Frame:Approximately 26 or 52 weeks
Safety Issue:
Description:USL311 in plasma and whole blood and lomustine in plasma

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Proximagen, LLC

Trial Keywords

  • 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

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