Recurrent Glioblastoma Multiforme (GBM)Phase 1GlioNCT04782609

Study of Icapamespib (PU-AD) in Patients With Recurrent Malignant Glioma

A Phase 1 study testing Icapamespib in people with Recurrent Glioblastoma Multiforme (GBM) and Grade 3 Isocitrate Dehydrogenase (IDH) Wildtype Astrocytoma, run by Samus Therapeutics, Inc. at 5 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

This is a 2-part multicenter Phase 1b study designed to test icapamespib in patients with recurrent brain lesions. Part 1 of the trial will be a standard 3 by 3 dose escalation design where different doses are examined. Part 2 will be a dose expansion cohort to further evaluate the recommended Phase 2 dose (RP2D). Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Recurrent Glioblastoma Multiforme (GBM), Grade 3 Isocitrate Dehydrogenase (IDH) Wildtype Astrocytoma, Grade 3 or 4 Astrocytoma
What is being tested?: Icapamespib
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 7 participants
Where: 5 sitesUnited States
Study dates: 27 Dec 2021to 4 Nov 2022
Phase: Phase 1
Are there results?: None posted in the registry

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

Male or female subjects having histologically confirmed IDH wildtype glioblastoma (Parts 1 and 2), or grade 3 or 4 IDH mutant astrocytoma (Part 1 only) per WHO criteria
Subjects must be at 1st, 2nd, or 3rd recurrence (Part 1) or 1st or 2nd recurrence (Part 2) and with at least 5 subjects clinically requiring reoperation for tumor progression (Part 2). ; Note: recurrence is defined as progression following initial therapy (i.e., radiation, chemotherapy, or radiation + chemotherapy); if the participant had a surgical resection for relapsed disease and no anti-tumor therapy instituted for up to 12 weeks, this is considered one recurrence.
Measurable disease as defined by modified RANO (1 cm × 1 cm minimum dimensions, at least 12 weeks after final radiotherapy dose; if new disease is outside radiotherapy field, <4 weeks is acceptable).
Cranial MRI performed within 14 days prior to study entry.
Age equal to or greater than 18 years
Karnofsky performance status of >60 at screening

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Adequate bone marrow, liver and renal functions (tests must be performed within 14 days prior to enrollment).The following laboratory values must be documented within 3 days prior to the first dose of study drug Absolute neutrophil count (ANC) ≥1.5 × 109/L Platelet count ≥100 × 109/L Estimated creatinine clearance (CrCl) >60 mL/min by Cockcroft-Gault formulation Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤1.5 × the upper limit of normal (ULN) Total bilirubin ≤1.5 × ULN (unless due to Gilbert's syndrome) Serum albumin ≥2.8 g/dL International normalized ratio (INR) <1.5 (except subjects maintained on anticoagulant medications)
Negative serum or urine pregnancy test (females of childbearing potential only).
Willingness to follow highly effective means of contraception
Able and willing to give informed consent

Who cannot join

Currently receiving any concomitant anti-cancer medication
Prior treatment with Gliadel wafers.
No radiation within 4 weeks of starting treatment.
Has tumor localized primarily to the brainstem or spinal cord.
A history of any other primary malignancy that has not been treated with curative intent and that has not been in complete remission for at least 2 years (exempt from the two year limit are non-melanoma skin cancer and cervical carcinoma in-situ on biopsy or a squamous intraepithelial lesion on PAP smear).
Active infection requiring systemic treatment.

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Any significant medical illnesses or toxicities that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patients' ability to tolerate this therapy. Patients must not have any disease that will obscure toxicity or dangerously alter drug metabolism, e.g. congestive heart failure, moderate to severe liver and renal disease, other cancers.
History of unstable angina, myocardial infarction, chronic heart failure (New York Heart Association Class III or IV) or clinically significant conduction abnormalities (e.g., unstable atrial fibrillation) within 1 year prior to Screening
QT interval corrected with the Fridericia formula (QTcF) on average of triplicate ECG readings (taken approximately 5 minutes apart) at Screening Visit ECG or Baseline Visit ECGs >450 msec for males or >470 msec for females (except when QT prolongation is associated with right or left bundle branch block, in which case enrollment is allowed).
Has active ocular condition unrelated to primary intracranial pathology, that in the opinion of the investigator, may alter visual acuity during the course of the study.
The need for concomitant use of long-acting gastric pH elevating agents (proton pump inhibitors or H2-receptor antagonists) at study entry and during the study (note: gastric locally-acting antacids may be allowed if administered >2 hours before or after dosing).
The need for concomitant use of any drugs that are sensitive substrates of CYP 450 isozymes with narrow therapeutic index for at least 7 days prior to administration of the first dose of IMP and throughout the study.
The need for concomitant use of any drugs that are strong inhibitors or inducers of cytochrome (CYP) 450 isozymes at least 7 days prior to administration of the first dose of IMP and throughout the study.
Has taken other investigational drugs or participated in any clinical study within 30 days or 5 half-lives (if known) of the investigational drug, whichever is longer, prior to first dose of IMP in this study; or is currently participating in another clinical study.
Has taken corticosteroids at greater than dexamethasone 4 mg daily or equivalent daily, participants taking <4 mg daily are eligible if the dose has been stable for ≥ 1 week before the first dose of study drug.
Other unspecified reasons that, in the opinion of the investigator or Samus and/or its delegated medical monitor, place the subject at risk or make the subject unsuitable for the study or unable or unwilling to comply with the requirements of the study
History or presence of conditions, which in the judgment of the investigator, are known to interfere with the absorption distribution, metabolism or excretion of drugs, such as prior surgery or gastrointestinal dysfunction that may affect drug absorption (e.g., gastric bypass surgery, gastrectomy)
Prior exposure to icapamespib or other Hsp90 inhibitors

Trial locations and contacts

5 sites in 1 country.

City, postcode or hospital

5 sites in 1 country

United States5 sites

MD Anderson Cancer Center
Houston, Texas, 77030
University of California, Las Angeles Medical Center
Los Angeles, California, 90027
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Huntsman Cancer Institute
Salt Lake City, Utah, 84112
University of California San Diego
San Diego, California, 92093

Other trials in United States

About this study

Official title: A Phase 1b Dose Escalation/Dose Expansion Study of Icapamespib (PU-AD) in Patients With Recurrent Malignant Glioma

This is a 2-part multicenter Phase 1b study designed to test icapamespib in patients with recurrent brain lesions.

Read the detailed description

This is a 2-part multicenter Phase 1b study designed to test the safety, tolerability and pharmacokinetics of single agent oral icapamespib in patients with recurrent brain lesions.

Part 1 of the trial will be a standard 3 by 3 dose escalation design where different doses are examined. Part 2 will be a dose expansion cohort to further evaluate the recommended Phase 2 dose (RP2D). The RP2D is defined as the dose level recommended for further clinical study, or the highest dose tested. The RP2D may be the same as the maximum tolerated dose (MTD) or modified from the MTD based on assessment of overall exposure, safety experience in Cycle 2 and beyond, and clinical benefit data in the study. The RP2D will be determined in the dose expansion phase of the study.

Part 1: Up to 30 patients with 1st, 2nd or 3rd recurrence of IDH wild type glioblastoma multiforme (GBM) or grade 3 or 4, Isocitrate dehydrogenase (IDH) mutant astrocytoma will be enrolled to evaluate the safety, pharmacokinetics (PK), pharmacodynamics, and MTD of single agent oral icapamespib administered daily.

Icapamespib will be administered orally once daily for each 28-day cycle. The initial dose in this trial will be 20 mg in Cohort 1. Dose escalation will proceed as follows:

100% increment until the first drug-related Grade 2 adverse event (AE) occurs, then
50% increment until the first drug-related Grade 3 event occurs, then
33% increment until the first Dose Limiting Toxicities (DLT) occurs, then
20% increment until RP2D is declared.

Conditions: Recurrent Glioblastoma Multiforme (GBM), Grade 3 Isocitrate Dehydrogenase (IDH) Wildtype Astrocytoma, Grade 3 or 4 Astrocytoma, Glioblastoma Surgery
Being tested: Icapamespib
Medical subject headings: Glioblastoma, Lymphoma, Follicular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

IcapamespibDrug
Also called Malignant Glioma
to test the safety, tolerability and pharmacokinetics of single agent oral icapamespib in patients with recurrent brain lesions.

Study groups in NCT04782609
Study group	Role	What they receive
20 mg Icapamespib cohort	Experimental	Icapamespib will be administered orally once daily for each 28-day cycle. The initial dose in this trial will be 20 mg Receives: Drug: Icapamespib
dose expansion cohort	Experimental	dose expansion cohort to further evaluate the recommended Phase 2 dose (RP2D) Receives: Drug: Icapamespib

What is being measured

The primary outcome is the main question the study is designed to answer.

Incidence and severity of adverse events
Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5
Measured: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 6 months
Maximum Tolerated Dose (MTD)/Coverage with evidence development (CED)/recommended phase 2 dose (RP2D) (Part 1 Only
Assessed by the occurrences of DLTs in doses of single agent icapamespib. The MTD will be defined as the dose that does not exceed an acceptable threshold of toxicity which is set at 33%. Scientific Review Committee (SRC) may elect to set the dose lower than MTD or in the absence of establishing MTD as the Recommended Phase 2 dose (RP2D).
Measured: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 6 months
Icapamespib Plasma Concentration at Time of Surgery
Tissue samples collected at surgery after icapamespib treatment.
Measured: 7-14 days post surgery

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

27 Dec 20214 Nov 2022

First posted4 Mar 2021
Study start27 Dec 2021
Primary completion4 Nov 2022
Study completion4 Nov 2022

Why it stopped: Samus Therapeutics Company Closure

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Recurrent Glioblastoma Multiforme (GBM)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
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Model description: Part 1 of the trial will be a standard 3 by 3 dose escalation design where different doses are examined. Part 2 will be a dose expansion cohort to further evaluate the recommended Phase 2 dose (RP2D). The RP2D is defined as the dose level recommended for further clinical study, or the highest dose tested. The RP2D may be the same as the MTD or modified from the MTD based on assessment of overall exposure, safety experience in Cycle 2 and beyond, and clinical benefit data in the study. The RP2D will be determined in the dose expansion phase of the study.
Masking: None (open label)
Enrolment: 7 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04782609
Sponsor's protocol ID: PU-AD-SD-0104
Acronym: Glio
Status last verified: Nov 2022
First submitted: 19 Feb 2021
Last updated: 17 Nov 2022
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 17 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 1b Dose Escalation/Dose Expansion Study of Icapamespib (PU-AD) in Patients With Recurrent Malignant Glioma
ClinicalTrials.gov ID: NCT04782609
Acronym / sponsor ID: Glio / PU-AD-SD-0104
Conditions: Recurrent Glioblastoma Multiforme (GBM), Grade 3 Isocitrate Dehydrogenase (IDH) Wildtype Astrocytoma, Grade 3 or 4 Astrocytoma, Glioblastoma Surgery
Phase: Phase 1
Study type: Interventional
Recruitment status: TerminatedReason stopped: Samus Therapeutics Company Closure
Enrolment: 7 participants (actual)
Lead sponsor: Samus Therapeutics, Inc.Industry (pharma, biotech, devices)
Study start: 27 Dec 2021 (actual)
Primary completion: 4 Nov 2022 (actual)
Study completion: 4 Nov 2022 (actual)
First posted: 4 Mar 2021 (actual)
Results: Not posted in the source record

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 2-part multicenter Phase 1b study designed to test icapamespib in patients with recurrent brain lesions.

Detailed description

This is a 2-part multicenter Phase 1b study designed to test the safety, tolerability and pharmacokinetics of single agent oral icapamespib in patients with recurrent brain lesions.

Icapamespib will be administered orally once daily for each 28-day cycle. The initial dose in this trial will be 20 mg in Cohort 1. Dose escalation will proceed as follows:

100% increment until the first drug-related Grade 2 adverse event (AE) occurs, then
50% increment until the first drug-related Grade 3 event occurs, then
33% increment until the first Dose Limiting Toxicities (DLT) occurs, then
20% increment until RP2D is declared.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Number of arms: 2
Model description: Part 1 of the trial will be a standard 3 by 3 dose escalation design where different doses are examined. Part 2 will be a dose expansion cohort to further evaluate the recommended Phase 2 dose (RP2D). The RP2D is defined as the dose level recommended for further clinical study, or the highest dose tested. The RP2D may be the same as the MTD or modified from the MTD based on assessment of overall exposure, safety experience in Cycle 2 and beyond, and clinical benefit data in the study. The RP2D will be determined in the dose expansion phase of the study.

Arm	Type	Receives
20 mg Icapamespib cohort	Experimental	Drug: IcapamespibIcapamespib will be administered orally once daily for each 28-day cycle. The initial dose in this trial will be 20 mg
dose expansion cohort	Experimental	Drug: Icapamespibdose expansion cohort to further evaluate the recommended Phase 2 dose (RP2D)

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (10 listed)

Male or female subjects having histologically confirmed IDH wildtype glioblastoma (Parts 1 and 2), or grade 3 or 4 IDH mutant astrocytoma (Part 1 only) per WHO criteria
Subjects must be at 1st, 2nd, or 3rd recurrence (Part 1) or 1st or 2nd recurrence (Part 2) and with at least 5 subjects clinically requiring reoperation for tumor progression (Part 2). ; Note: recurrence is defined as progression following initial therapy (i.e., radiation, chemotherapy, or radiation + chemotherapy); if the participant had a surgical resection for relapsed disease and no anti-tumor therapy instituted for up to 12 weeks, this is considered one recurrence.
Measurable disease as defined by modified RANO (1 cm × 1 cm minimum dimensions, at least 12 weeks after final radiotherapy dose; if new disease is outside radiotherapy field, <4 weeks is acceptable).
Cranial MRI performed within 14 days prior to study entry.
Age equal to or greater than 18 years

Key exclusion criteria (18 listed)

Currently receiving any concomitant anti-cancer medication
Prior treatment with Gliadel wafers.
No radiation within 4 weeks of starting treatment.
Has tumor localized primarily to the brainstem or spinal cord.
A history of any other primary malignancy that has not been treated with curative intent and that has not been in complete remission for at least 2 years (exempt from the two year limit are non-melanoma skin cancer and cervical carcinoma in-situ on biopsy or a squamous intraepithelial lesion on PAP smear).

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
IcapamespibAlso: Malignant Gliomato test the safety, tolerability and pharmacokinetics of single agent oral icapamespib in patients with recurrent brain lesions.	Drug	20 mg Icapamespib cohort, dose expansion cohort

Primary outcome

Incidence and severity of adverse events
Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 6 months
Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5
Maximum Tolerated Dose (MTD)/Coverage with evidence development (CED)/recommended phase 2 dose (RP2D) (Part 1 Only
Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 6 months
Assessed by the occurrences of DLTs in doses of single agent icapamespib. The MTD will be defined as the dose that does not exceed an acceptable threshold of toxicity which is set at 33%. Scientific Review Committee (SRC) may elect to set the dose lower than MTD or in the absence of establishing MTD as the Recommended Phase 2 dose (RP2D).
Icapamespib Plasma Concentration at Time of Surgery
Time frame: 7-14 days post surgery
Tissue samples collected at surgery after icapamespib treatment.

Results and safety

The study was stopped early (reason given: Samus Therapeutics Company Closure). Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 17 Nov 2022.
Individual participant dataSharing planned: No

Related trials for Recurrent Glioblastoma Multiforme (GBM)

RecruitingPhase 1/2
Testing the Addition of an Anti-cancer Drug, Selinexor, to the Usual Chemotherapy Treatment (Temozolomide) for Brain Tumors That Have Returned After Previous Treatment
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PLX038 in Primary Central Nervous System Tumors Containing MYC or MYCN Amplifications
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RecruitingObservational study
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RecruitingPhase 1
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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.

Michael Silverman, MD study director

Samus Therapeutics

5 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 10 inclusion and 18 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 17 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. 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 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.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Samus Therapeutics Company Closure). Results are not available in the source record.

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?

Incidence and severity of adverse events (time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 6 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04782609.

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 17 Nov 2022.