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

NCT02765165 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: P311-201
• Study Type: interventional
• Target: 26
• Locations: 2 countries
• Sites: 6

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.

Conditions

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

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

Outcome Measures

Primary Outcomes (2)

• Phase 1: Maximum Tolerated Dose (MTD)

  The MTD was defined as the highest safe dose (mg/m\^2) administered where safe is defined by having at least a 50% probability that the dose limiting toxicity (DLT) rate is less than 33%, as determined by a modified continuous reassessment model.

  Assessed weekly during treatment period. Median duration of exposure was 5.14 (range 2.1-17.3) weeks.

• Phase 1: Maximum Tolerated Dose (MTD)

  The MTD was defined as the highest safe dose (mg) administered where safe is defined by having at least a 50% probability that the dose limiting toxicity (DLT) rate is less than 33%, as determined by a modified continuous reassessment model.

  Assessed weekly during treatment period. Median duration of exposure was 6.00 (range 0.3-30.0) weeks.

Secondary Outcomes (7)

• Percentage Progression Free Survival (PFS) at 6 Months (PFS-6m)

  Once every 6 weeks during treatment

• Overall Survival (OS)

  Weekly during treatment or every 12 weeks during follow-up

• Median Progression Free Survival (PFS)

  Every 6 weeks during treatment

• Objective Response Rate (ORR%)

  Every 6 weeks

• Peak Concentration (Cmax)

  Day 1

Study Arms (5)

Dose-Escalation USL311, Solid Tumor, Part 1a

EXPERIMENTAL

USL311, intravenous, once per week, starting at 60 mg/m˄2

Drug: USL311

Dose-Escalation USL311, Solid Tumor, Part 1b

EXPERIMENTAL

USL311, oral, daily, starting at 40 mg

Drug: USL311

Dose-Escalation USL311 with Lomustine, Solid Tumor, Part 2

EXPERIMENTAL

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; Drug: Lomustine

Dose-Expansion, USL311, GBM, Part 3

EXPERIMENTAL

USL311, oral, daily, starting at dose determined in Part 1b

Drug: USL311

Dose-Expansion, USL311 with Lomustine, GBM, Part 4

EXPERIMENTAL

USL311, oral, daily, in combination with lomustine, oral, once every 6 weeks, at dose(s) as determined in part 2

Drug: USL311; Drug: Lomustine

Interventions

USL311 DRUG

Administered once weekly in a 21-day cycle

Dose-Escalation USL311, Solid Tumor, Part 1a

Lomustine DRUG

Administered once every 6 weeks in a 42-day cycle

Dose-Escalation USL311 with Lomustine, Solid Tumor, Part 2; Dose-Expansion, USL311 with Lomustine, GBM, Part 4

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All Subjects:
• Provide signed and dated informed consent prior to study-specific screening procedures
• ≥ 18 years old
• Karnofsky performance status (KPS) ≥ 70
• Must have adequate bone marrow and renal/hepatic function within protocol specified limits
• 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
• Women and men must use protocol approved methods of contraception
• Must be able and willing to comply with the study visit schedule and study procedures
• Must be able to take oral medications
• Must have available archived tumor tissue and willing and able to provide consent for study access to such tissue
• For subjects with a history of seizures, must be adequately controlled on a stable regimen of anti-epileptic drugs
• For Phase 1 Subjects Only:
• 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
• Inoperable metastatic or locally advanced, unresectable disease
• Subjects may have either evaluable or measurable disease

You may not qualify if:

• All Subjects
• 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
• 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)
• Subjects taking any strong cytochrome P450 3A4 inducers within 14 days prior to the first dose of study drug(s)
• Subjects taking any strong cytochrome P450 3A4 inhibitors within 14 days prior to the first dose of study drug(s)
• 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)
• 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)
• 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)
• History of significant cardiac disease
• Status epilepticus within 1 year prior to the first dose of study drug(s)
• Pregnant or breastfeeding
• Any other significant co-morbid conditions that in the opinion of the Investigator would impair study participation or cooperation
• For Phase 1 Subjects Only:
• Lymphoma as primary cancer
• For Phase 2 Subjects Only:

Sponsors & Collaborators

• Proximagen, LLC: lead

Study Sites (6)

Washington University

St Louis, Missouri, 63110, United States

Location

University of Oklahoma Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104, United States

Location

University of Texas/MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

South Texas Accelerated Research Therapeutics (START)

San Antonio, Texas, 78229, United States

Location

UT Health San Antonio Cancer Center

San Antonio, Texas, 78229, United States

Location

South Texas Accelerated Research Therapeutics (START) - FJD

Madrid, Spain

Location

MeSH Terms

Conditions

Recurrence; Glioblastoma; Brain Neoplasms; Neoplasms

Interventions

Lomustine

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Nitrosourea Compounds; Urea; Amides; Organic Chemicals; Nitroso Compounds

Limitations and Caveats

Small cohort sample size. Heterogenous solid tumor types.

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Proximagen, LLC

tcmeng@proximagen.com

952-658-7440

Study Officials

• Tze-Chiang Meng, MD

  Proximagen, LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 19, 2016
• First Posted: May 6, 2016
• Study Start: April 1, 2016
• Primary Completion: July 1, 2020
• Study Completion: July 1, 2020
• Last Updated: July 23, 2021
• Results First Posted: July 23, 2021

Record last verified: 2021-07

Locations

US (5); ES (1)