Solid Tumors (Phase 1)Phase 1/2NCT02765165
Phase 1/2 Study of USL311 +/- Lomustine in Advanced Solid Tumors or Relapsed/Recurrent Glioblastoma Multiforme (GBM)
A Phase 1/2 study testing USL311 and Lomustine in people with Solid Tumors (Phase 1) and Relapsed/Recurrent GBM (Phase 2), run by Proximagen, LLC at 6 sites in 2 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumors (Phase 1), Relapsed/Recurrent GBM (Phase 2)
- What is being tested?
- USL311 and Lomustine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 6 sitesin 2 countries
- Study dates
- Apr 2016to 1 Jul 2020
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
- 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:
- Histologically confirmed diagnosis of GBM
- Subjects must have documented recurrence after first-line treatment
- Prior first-line treatment must have included radiation and temozolomide
- Subject is suitable for re-resection, per Investigator discretion, as a component of their clinical care
- No more than one prior resection (Note: biopsy does not count as prior resection)
Who cannot join
- 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)
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- 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:
- Unable or unwilling to consent to the provision of resected tissue after surgery
- Prior treatment with plerixafor or another CXCR4 inhibitor
- Prior treatment with bevacizumab
- Prior treatment with lomustine and/or carmustine
- For All Cohorts Receiving Oral USL311:
- 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 locations and contacts
6 sites in 2 countries.
6 sites in 2 countries
United States5 sites
University of Texas/MD Anderson Cancer Center
Houston, Texas, 77030
University of Oklahoma Stephenson Cancer Center
Oklahoma City, Oklahoma, 73104
South Texas Accelerated Research Therapeutics (START)
San Antonio, Texas, 78229
UT Health San Antonio Cancer Center
San Antonio, Texas, 78229
Washington University
St Louis, Missouri, 63110
About this study
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)
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.
- Being tested
- USL311, Lomustine
- 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
- Medical subject headings
- Recurrence, Glioblastoma, Brain Neoplasms, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
USL311Drug
Administered once weekly in a 21-day cycle
USL311Drug
Administered once daily in a 21-day cycle
USL311Drug
Administered once daily in a 42-day cycle
LomustineDrug
Administered once every 6 weeks in a 42-day cycle
| Study group | Role | What they receive |
|---|---|---|
| Dose-Escalation USL311, Solid Tumor, Part 1a | Experimental | USL311, intravenous, once per week, starting at 60 mg/m˄2 Receives: Drug: USL311 |
| Dose-Escalation USL311, Solid Tumor, Part 1b | Experimental | USL311, oral, daily, starting at 40 mg Receives: 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 Receives: Drug: USL311; Drug: Lomustine |
| Dose-Expansion, USL311, GBM, Part 3 | Experimental | USL311, oral, daily, starting at dose determined in Part 1b Receives: 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 Receives: Drug: USL311; Drug: Lomustine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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)
Percentage of subjects who were without progression at 6 months as assessed radiographically with response to treatment determined by Response Evaluation Criteria in Solid Tumors (RECIST) or Response Assessment in Neuro-Oncology (RANO) criteria.
Measured: Once every 6 weeks during treatment
Overall Survival (OS)
Percentage of subjects alive five years after start of treatment.
Measured: Weekly during treatment or every 12 weeks during follow-up
Median Progression Free Survival (PFS)
Time after initiation of treatment before disease progression
Measured: Every 6 weeks during treatment
Objective Response Rate (ORR%)
Percentage of patients whose disease decreased (Partial response) and/or disappears (Complete response) after initiation of treatment
Measured: Every 6 weeks
Peak Concentration (Cmax)
Peak USL311 concentration (Cmax) in plasma
Measured: Day 1
Time to Peak Concentration (Tmax)
Time to peak concentration of USL311 in plasma
Measured: Day 1
Area Under the Concentration Versus Time Curve (AUC)
Area under the curve versus time from time 0 to infinity for USL311 concentration in plasma
Measured: Day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2016 (estimated)
- Study startApr 2016
- Primary completion1 Jul 2020
- Study completion1 Jul 2020
Why it stopped: Business reasons not related to safety
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Solid Tumors (Phase 1)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Proximagen, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Tze-Chiang Meng, MD, Study director, Proximagen, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02765165
- Sponsor's protocol ID
- P311-201
- Status last verified
- Jul 2021
- First submitted
- 19 Apr 2016
- Last updated
- 23 Jul 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT02765165
- Acronym / sponsor ID
- P311-201
- Keywords
- Phase 1, Phase 2, Glioblastoma Multiforme, Glioblastoma, GBM, Brain Tumor, Brain Cancer, Tumor
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Business reasons not related to safety
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Proximagen, LLCIndustry (pharma, biotech, devices)
- Study start
- Apr 2016 (actual)
- Primary completion
- 1 Jul 2020 (actual)
- Study completion
- 1 Jul 2020 (actual)
- First posted
- 6 May 2016 (estimated)
- Results
- Posted 23 Jul 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Dose-Escalation USL311, Solid Tumor, Part 1a | Experimental | Drug: USL311USL311, intravenous, once per week, starting at 60 mg/m˄2 |
| Dose-Escalation USL311, Solid Tumor, Part 1b | Experimental | Drug: USL311USL311, oral, daily, starting at 40 mg |
| Dose-Escalation USL311 with Lomustine, Solid Tumor, Part 2 | Experimental | Drug: USL311, Drug: LomustineUSL311, oral, daily, starting at dose as determined in Part 1b, in combination with lomustine 90 mg/m˄2, oral, once every 6 weeks |
| Dose-Expansion, USL311, GBM, Part 3 | Experimental | Drug: USL311USL311, oral, daily, starting at dose determined in Part 1b |
| Dose-Expansion, USL311 with Lomustine, GBM, Part 4 | Experimental | Drug: USL311, Drug: LomustineUSL311, oral, daily, in combination with lomustine, oral, once every 6 weeks, at dose(s) as determined in part 2 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- 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
Key exclusion criteria (21 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| USL311Administered once weekly in a 21-day cycle | Drug | Dose-Escalation USL311, Solid Tumor, Part 1a |
| USL311Administered once daily in a 21-day cycle | Drug | Dose-Escalation USL311, Solid Tumor, Part 1b, Dose-Expansion, USL311, GBM, Part 3 |
| USL311Administered once daily in a 42-day cycle | Drug | Dose-Escalation USL311 with Lomustine, Solid Tumor, Part 2, Dose-Expansion, USL311 with Lomustine, GBM, Part 4 |
| LomustineAdministered once every 6 weeks in a 42-day cycle | Drug | Dose-Escalation USL311 with Lomustine, Solid Tumor, Part 2, Dose-Expansion, USL311 with Lomustine, GBM, Part 4 |
Primary outcome
Phase 1: Maximum Tolerated Dose (MTD)
Time frame: Assessed weekly during treatment period. Median duration of exposure was 5.14 (range 2.1-17.3) weeks.
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.
Phase 1: Maximum Tolerated Dose (MTD)
Time frame: Assessed weekly during treatment period. Median duration of exposure was 6.00 (range 0.3-30.0) weeks.
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.
7 secondary outcomes
Percentage Progression Free Survival (PFS) at 6 Months (PFS-6m)
Time frame: Once every 6 weeks during treatment
Overall Survival (OS)
Time frame: Weekly during treatment or every 12 weeks during follow-up
Median Progression Free Survival (PFS)
Time frame: Every 6 weeks during treatment
Objective Response Rate (ORR%)
Time frame: Every 6 weeks
Peak Concentration (Cmax)
Time frame: Day 1
Time to Peak Concentration (Tmax)
Time frame: Day 1
Area Under the Concentration Versus Time Curve (AUC)
Time frame: Day 1
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jul 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tze-Chiang Meng, MD study director
Proximagen, LLC
6 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing USL311 and Lomustine in people with Solid Tumors (Phase 1) and Relapsed/Recurrent GBM (Phase 2), run by Proximagen, LLC at 6 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 23 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Jul 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase 1: Maximum Tolerated Dose (MTD) (time frame: Assessed weekly during treatment period. Median duration of exposure was 5.14 (range 2.1-17.3) weeks.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jul 2021.