Glioblastoma MultiformePhase 1NCT03332355
Procaspase Activating Compound-1 (PAC-1) in the Treatment of Advanced Malignancies - Component 2
A Phase 1 study testing PAC-1 Compound in people with Glioblastoma Multiforme and Anaplastic Astrocytoma, run by Vanquish Oncology, Inc. at 3 sites in United States.
Trial summary
The primary objectives of this study are to determine the maximal tolerated dose (MTD) of PAC-1 in combination with temozolomide in patients with high grade glioma: glioblastoma multiforme (GBM) or anaplastic astrocytoma after progression following standard first line therapy (Component 2), by evaluation of toxicity… Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Glioblastoma Multiforme, Anaplastic Astrocytoma
- What is being tested?
- PAC-1 Compound
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 3 sitesUnited States
- Study dates
- 1 Oct 2017to 31 Dec 2021
- 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 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female ≥ 18 years of age
- Diagnosis of advanced solid tumor or hematologic malignancy (limited to lymphoma) that has failed or become intolerant to standard therapy (Component 1 - single agent PAC-1) Note: Gliomas are excluded from Component 1 (see exclusion #19)
- Diagnosis of high grade glioma: glioblastoma multiforme (GBM) or anaplastic astrocytoma after progression following treatment with standard first line therapy (Component 2 - PAC-1 in combination with temozolomide).
- Has measurable disease, defined as at least 1 tumor that fulfills the criteria for a target lesion according to RECIST 1.1 (Component 1).
- For patients in study Component 2 measurable disease RANO criteria will be used.
- Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 (see Appendix 4)
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- Has adequate hepatic function defined as total bilirubin < 1.5 mg/dL, serum albumin > 3.0 gm/dL, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 1.5 × upper limit of normal (ULN) or < 3 x ULN for subjects with known hepatic metastases
- Has adequate renal function defined as serum creatinine < 1.5 × ULN
- Has adequate bone marrow function defined as a hemoglobin ≥ 10 g/dL, absolute neutrophil count (ANC) ≥ 1.5 × 109/L, and platelet count ≥ 100 × 109/L
- Patients taking antiepileptic drugs (AED) must be on stable doses of AED for at least two weeks prior to registration and have no episode of seizures for at least 14 days prior to registration. Because some AEDs enhance or inhibit enzymes that may affect PAC-1 metabolism, those AEDs will not be permitted in this study. The AEDs that are and are not permissible are in Appendix 6.
- Patient must be able to take oral medication and to maintain a fast as required for 2 hours before and 1 hour after capsule(s) administration
- Must be willing and able to comply with study visits and procedures
- Has read, understood and signed the informed consent form (ICF) approved by the Institutional Review Board/Independent Ethics Committee (IRB/IEC)
- Women of childbearing potential (WOCP) must not be pregnant (confirmed by a negative pregnancy test, with a serum B-HCG with a sensitivity of 50 mL U/L within 7 days of study treatment) or breast-feeding. In addition, a medically acceptable method of birth control must be used such as an oral, implantable, injectable, or transdermal hormonal contraceptive, an intrauterine device (IUD), use of a double barrier method (condoms, sponge, diaphragm, or vaginal ring with spermicidal jellies or cream), or total abstinence during the study participation and for one month after last dose of study drug(s). Women who are postmenopausal for at least 1 year or surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy) are not considered to be WOCP.
- Men who are not surgically or medically sterile must agree to use an acceptable method of contraception. Male patients with female sexual partners who are pregnant, possibly pregnant, or who could become pregnant during the study must agree to use condoms at least one month after the last dose of study drug. Total abstinence for the same study period is an acceptable alternative.
- Prior systemic treatments for metastatic disease are permitted but may not be ongoing, including targeted therapies, biologic response modifiers, chemotherapy, hormonal therapy, or investigational therapy (see Exclusion #20).
- Willingness to donate blood for biomarker studies related to the type of therapies used in this trial and the tumor types being treated
Who cannot join
- Had surgery within 4 weeks prior to study treatment except for minor procedures (hepatic biliary stent placement is allowed)
- For Component 1 (PAC-1 alone), gliomas are excluded, as well as any history of brain metastases, seizures or underlying brain injury (e.g., traumatic brain injury, or hemorrhagic or ischemic stroke)
- Patients may not have received cytotoxic chemotherapy, targeted therapies, biologic response modifiers, chemotherapy, and hormonal therapy within the last 3 weeks, or nitrosureas within the last 6 weeks prior to study treatment.
- Has a known hypersensitivity to temozolomide (this criterion applies only in Component 2)
- Has a history of blood clots, pulmonary embolism, or deep vein thrombosis unless controlled by anticoagulant treatment (patient must be on stable dose for 2 weeks)
- Has a history of an arterial thromboembolic event within the prior six months including cerebrovascular accident, transient ischemic attack, myocardial infarction, or unstable angina.
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- Has uncontrolled human immunodeficiency virus (HIV) (defined as HIV RNA >500 copies/ml and CD4+ count<200/mm3 on antiretroviral therapy) infection or hepatitis B (defined as ALT > 1 x ULN, and HBV DNA >2000 IU/ml) or hepatitis C (defined as ALT > 1 x ULN, persistent viremia on antiviral therapy) infections.
- Has any clinically significant infection, i.e., any acute viral, bacterial, or fungal infection that requires specific treatment (anti-infective treatment has to be completed ≥ 7 days prior to study entry)
- Has any other severe, uncontrolled medical condition, including uncontrolled diabetes mellitus (defined as a Hemoglobin A1C≥ 9% in patients with a prior history of diabetes, 28 days prior to study ) or clinical signs of unstable congestive heart failure (Stage III-IV of the New York Heart Association Functional Classification) (Appendix 5).
- Radiation therapy to more than 25% of the bone marrow. Whole pelvic radiation is considered to be over 25%.
- Prior allogeneic bone marrow or organ transplantation.
- > Grade 1 peripheral neuropathy within 14 days before enrollment.
- Pregnant or breastfeeding - temozolomide is Pregnancy Category D - can cause fetal harm. Confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
- Patient has received other investigational drugs within 14 days prior to study treatment.
- Other severe acute or chronic medical or psychiatric conditions or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for enrollment in this study.
- Abnormalities on 12-lead electrocardiogram (ECG) considered by the investigator to be clinically significant (such as acute ischemia, left bundle branch block, ventricular arrhythmias) or baseline prolongation of the rate-corrected QT interval (e.g., repeated demonstration of QTc interval > 480 milliseconds).
- Presence of any non-healing wound, fracture, or ulcer within 28 days prior to the first dose of study drug.
- Has any condition that, in the opinion of the investigator, might jeopardize the safety of the patient or interfere with protocol compliance
- Has any mental or medical condition that prevents the patient from giving informed consent or participating in the trial
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Johns Hopkins Cancer Center
Baltimore, Maryland, 21231
University of Illinois at Chicago
Chicago, Illinois, 60612
Regions Hospital
Saint Paul, Minnesota, 55101
About this study
Official title: (STM-03) Phase I Study of Procaspase Activating Compound-1 (PAC-1) in the Treatment of Advanced Malignancies - Component 2
The primary objectives of this study are to determine the maximal tolerated dose (MTD) of PAC-1 in combination with temozolomide in patients with high grade glioma: glioblastoma multiforme (GBM) or anaplastic astrocytoma after progression following standard first line therapy (Component 2), by evaluation of toxicity and tolerability.
Read the detailed description
PAC-1 in combination with temozolomide (Component 2): after the MTD is established for single agent PAC-1 in Component 1, a modified-Fibonacci dose-escalation 3+3 design starts in Component 2, at a PAC-1 dose one level lower than the MTD of PAC-1 established in the single agent PAC-1 component (i.e., Component 1) and 150 mg/m2 dose of temozolomide given for the 5 days starting at day 8 of cycle 1 in cohorts of 3-6 patients. The combination cohort that reaches MTD will expanded to at least 9 patients, similar to the PAC-1 alone cohort at MTD. For all dose cohorts, pharmacokinetics of PAC-1 will be assessed following doses administered on days 1 and 11 of the first cycle. Temozolomide pharmacokinetics will be performed on Day 11 of the first cycle.
- Conditions
- Glioblastoma Multiforme, Anaplastic Astrocytoma
- Being tested
- PAC-1 Compound
- Keywords
- glioblastoma multiforme, anaplastic astrocytoma, high grade glioma, temozolomide, PROCASPASE ACTIVATING COMPOUND-1 (PAC-1), advanced malignancy, maximal tolerated dose (MTD)
- Medical subject headings
- Glioblastoma, Astrocytoma, Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PAC-1 CompoundDrug
Also called Temozolamide
PAC-1 in combination with temozolomide (Component 2): after the MTD is established for single agent PAC-1 in Component 1, a modified-Fibonacci dose-escalation 3+3 design starts in Component 2, at a PAC-1 dose one level lower than the MTD of PAC-1 established in the single agent PAC-1 component (i.e., Component 1). PAC-1 will be taken in the morning on days 1-21 in each 28 day cycle. Temozolomide 150 mg/m2 dose is given for the 5 days starting at day 8 of cycle 1 in cohorts of 3-6 patients. The combination cohort that reaches MTD will expanded to at least 9 patients, similar to the PAC-1 alone cohort at MTD.
| Study group | Role | What they receive |
|---|---|---|
| PAC-1 in combination with temozolomide | Experimental | Temozolomide (PO) will be dosed at 150 mg (adjusted for body size area [m2]) daily for 5 days starting on day 8 at cycle 1, and then for each successive cycle. In Component 2, the first PAC-1 dose will be 1 dose level lower than the PAC-1 MTD established in Component 1, and the maximum dose will not exceed 450 mg. PAC-1 will be taken in the morning on days 1-21 in each 28-day cycle. Receives: Drug: PAC-1 Compound |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD)
MTD, defined as the highest tolerated dose of PAC-1 tested in combination with temozolomide in patients with high grade glioma.
Measured: During treatment cycle 1 (first 28 days)
Secondary outcomes (2)
Adverse Effects
Toxicity will be graded using the Common Terminology Criteria for Adverse Events version 4 (CTCAE v4)
Measured: Up to 30 days post final dose
Disease Response
Disease response will be assessed by RANO criteria.
Measured: Through study completion, an average of one year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Nov 2017
- Study start1 Oct 2017
- Primary completion31 Dec 2021
- Study completion31 Dec 2021
Why it stopped: Business Reasons
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Glioblastoma MultiformeStudies 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
- Not applicable
- Intervention model
- Single group
- Model description
- PAC-1 in combination with temozolomide (Component 2): after the MTD is established for single agent PAC-1 in Component 1, a modified-Fibonacci dose-escalation 3+3 design starts in Component 2, at a PAC-1 dose one level lower than the MTD of PAC-1 established in the single agent PAC-1 component (i.e., Component 1) and 150 mg/m2 dose of temozolomide given for the 5 days starting at day 8 of cycle 1 in cohorts of 3-6 patients. The combination cohort that reaches MTD will expanded to at least 9 patients, similar to the PAC-1 alone cohort at MTD.
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanquish Oncology, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- University of Illinois Chicago
- Responsible party
- Sponsor
- Investigators
- Oana C Danciu, M.D., Principal investigator, Unversity of Illinois at Chicago
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03332355
- Sponsor's protocol ID
- 2017-0058
- Status last verified
- Jun 2022
- First submitted
- 16 Oct 2017
- Last updated
- 24 May 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- (STM-03) Phase I Study of Procaspase Activating Compound-1 (PAC-1) in the Treatment of Advanced Malignancies - Component 2
- ClinicalTrials.gov ID
- NCT03332355
- Acronym / sponsor ID
- 2017-0058
- Conditions
- Glioblastoma Multiforme, Anaplastic Astrocytoma
- Keywords
- glioblastoma multiforme, anaplastic astrocytoma, high grade glioma, temozolomide, PROCASPASE ACTIVATING COMPOUND-1 (PAC-1), advanced malignancy, maximal tolerated dose (MTD)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Business Reasons
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Vanquish Oncology, Inc.Industry (pharma, biotech, devices)
- Collaborators
- University of Illinois Chicago
- Study start
- 1 Oct 2017 (actual)
- Primary completion
- 31 Dec 2021 (actual)
- Study completion
- 31 Dec 2021 (actual)
- First posted
- 6 Nov 2017 (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.
The primary objectives of this study are to determine the maximal tolerated dose (MTD) of PAC-1 in combination with temozolomide in patients with high grade glioma: glioblastoma multiforme (GBM) or anaplastic astrocytoma after progression following standard first line therapy (Component 2), by evaluation of toxicity and tolerability.
Detailed description
PAC-1 in combination with temozolomide (Component 2): after the MTD is established for single agent PAC-1 in Component 1, a modified-Fibonacci dose-escalation 3+3 design starts in Component 2, at a PAC-1 dose one level lower than the MTD of PAC-1 established in the single agent PAC-1 component (i.e., Component 1) and 150 mg/m2 dose of temozolomide given for the 5 days starting at day 8 of cycle 1 in cohorts of 3-6 patients. The combination cohort that reaches MTD will expanded to at least 9 patients, similar to the PAC-1 alone cohort at MTD. For all dose cohorts, pharmacokinetics of PAC-1 will be assessed following doses administered on days 1 and 11 of the first cycle. Temozolomide pharmacokinetics will be performed on Day 11 of the first cycle.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- PAC-1 in combination with temozolomide (Component 2): after the MTD is established for single agent PAC-1 in Component 1, a modified-Fibonacci dose-escalation 3+3 design starts in Component 2, at a PAC-1 dose one level lower than the MTD of PAC-1 established in the single agent PAC-1 component (i.e., Component 1) and 150 mg/m2 dose of temozolomide given for the 5 days starting at day 8 of cycle 1 in cohorts of 3-6 patients. The combination cohort that reaches MTD will expanded to at least 9 patients, similar to the PAC-1 alone cohort at MTD.
| Arm | Type | Receives |
|---|---|---|
| PAC-1 in combination with temozolomide | Experimental | Drug: PAC-1 CompoundTemozolomide (PO) will be dosed at 150 mg (adjusted for body size area [m2]) daily for 5 days starting on day 8 at cycle 1, and then for each successive cycle. In Component 2, the first PAC-1 dose will be 1 dose level lower than the PAC-1 MTD established in Component 1, and the maximum dose will not exceed 450 mg. PAC-1 will be taken in the morning on days 1-21 in each 28-day cycle. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Male or female ≥ 18 years of age
- Diagnosis of advanced solid tumor or hematologic malignancy (limited to lymphoma) that has failed or become intolerant to standard therapy (Component 1 - single agent PAC-1) Note: Gliomas are excluded from Component 1 (see exclusion #19)
- Diagnosis of high grade glioma: glioblastoma multiforme (GBM) or anaplastic astrocytoma after progression following treatment with standard first line therapy (Component 2 - PAC-1 in combination with temozolomide).
- Has measurable disease, defined as at least 1 tumor that fulfills the criteria for a target lesion according to RECIST 1.1 (Component 1).
- For patients in study Component 2 measurable disease RANO criteria will be used.
Key exclusion criteria (19 listed)
- Had surgery within 4 weeks prior to study treatment except for minor procedures (hepatic biliary stent placement is allowed)
- For Component 1 (PAC-1 alone), gliomas are excluded, as well as any history of brain metastases, seizures or underlying brain injury (e.g., traumatic brain injury, or hemorrhagic or ischemic stroke)
- Patients may not have received cytotoxic chemotherapy, targeted therapies, biologic response modifiers, chemotherapy, and hormonal therapy within the last 3 weeks, or nitrosureas within the last 6 weeks prior to study treatment.
- Has a known hypersensitivity to temozolomide (this criterion applies only in Component 2)
- Has a history of blood clots, pulmonary embolism, or deep vein thrombosis unless controlled by anticoagulant treatment (patient must be on stable dose for 2 weeks)
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 |
|---|---|---|
| PAC-1 CompoundAlso: TemozolamidePAC-1 in combination with temozolomide (Component 2): after the MTD is established for single agent PAC-1 in Component 1, a modified-Fibonacci dose-escalation 3+3 design starts in Component 2, at a PAC-1 dose one level lower than the MTD of PAC-1 established in the single agent PAC-1 component (i.e., Component 1). PAC-1 will be taken in the morning on days 1-21 in each 28 day cycle. Temozolomide 150 mg/m2 dose is given for the 5 days starting at day 8 of cycle 1 in cohorts of 3-6 patients. The combination cohort that reaches MTD will expanded to at least 9 patients, similar to the PAC-1 alone cohort at MTD. | Drug | PAC-1 in combination with temozolomide |
Primary outcome
Maximum Tolerated Dose (MTD)
Time frame: During treatment cycle 1 (first 28 days)
MTD, defined as the highest tolerated dose of PAC-1 tested in combination with temozolomide in patients with high grade glioma.
2 secondary outcomes
Adverse Effects
Time frame: Up to 30 days post final dose
Disease Response
Time frame: Through study completion, an average of one year
Results and safety
The study was stopped early (reason given: Business Reasons). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 May 2023.
- Individual participant dataSharing planned: No
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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.
Oana C Danciu, M.D. principal investigator
Unversity of Illinois at Chicago
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing PAC-1 Compound in people with Glioblastoma Multiforme and Anaplastic Astrocytoma, run by Vanquish Oncology, Inc. at 3 sites in United States.
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 17 inclusion and 19 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 24 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 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: Business Reasons). 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?
Maximum Tolerated Dose (MTD) (time frame: During treatment cycle 1 (first 28 days)). 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 24 May 2023.