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Phase 1/2 Study of USL311 +/- Lomustine in Advanced Solid Tumors or Relapsed/Recurrent Glioblastoma Multiforme (GBM)

P

Proximagen

Status and phase

Terminated
Phase 2
Phase 1

Conditions

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

Treatments

Drug: Lomustine
Drug: USL311

Study type

Interventional

Funder types

Industry

Identifiers

NCT02765165
P311-201

Details and patient eligibility

About

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.

Enrollment

26 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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 QT corrected (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

Trial design

Primary purpose

Treatment

Allocation

Non-Randomized

Interventional model

Single Group Assignment

Masking

None (Open label)

26 participants in 5 patient groups

Dose-Escalation USL311, Solid Tumor, Part 1a
Experimental group
Description:
USL311, intravenous, once per week, starting at 60 mg/m˄2
Treatment:
Drug: USL311
Drug: USL311
Drug: USL311
Dose-Escalation USL311, Solid Tumor, Part 1b
Experimental group
Description:
USL311, oral, daily, starting at 40 mg
Treatment:
Drug: USL311
Drug: USL311
Drug: USL311
Dose-Escalation USL311 with Lomustine, Solid Tumor, Part 2
Experimental group
Description:
USL311, oral, daily, starting at dose as determined in Part 1b, in combination with lomustine 90 mg/m˄2, oral, once every 6 weeks
Treatment:
Drug: Lomustine
Drug: USL311
Drug: USL311
Drug: USL311
Dose-Expansion, USL311, GBM, Part 3
Experimental group
Description:
USL311, oral, daily, starting at dose determined in Part 1b
Treatment:
Drug: USL311
Drug: USL311
Drug: USL311
Dose-Expansion, USL311 with Lomustine, GBM, Part 4
Experimental group
Description:
USL311, oral, daily, in combination with lomustine, oral, once every 6 weeks, at dose(s) as determined in part 2
Treatment:
Drug: Lomustine
Drug: USL311
Drug: USL311
Drug: USL311

Trial documents
2

Trial contacts and locations

6

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Data sourced from clinicaltrials.gov

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