Solid TumorPhase 1NCT02355535
Procaspase Activating Compound-1 (PAC-1) in the Treatment of Advanced Malignancies - Component 1
A Phase 1 study testing PAC-1 in people with Solid Tumor and Pancreatic Neuroendocrine Tumor, run by Vanquish Oncology, Inc. at 3 sites in United States.
Trial summary
This Phase I dose escalation study will evaluate Procaspase Activating Compound-1 (PAC-1), a small molecule that activates procaspase -3 to caspase-3, resulting in apoptosis of cancer cells, in patients with advanced malignancies. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Solid Tumor, Pancreatic Neuroendocrine Tumor, Neuroendocrine Tumors
- What is being tested?
- PAC-1
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 3 sitesUnited States
- Study dates
- Feb 2015to 18 May 2020
- 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
- Has measurable disease, defined as at least 1 tumor that fulfills the criteria for a target lesion according to RECIST 1.1, or lymphoma that fulfills the Deauville PET Criteria
- Has an ECOG PS of 0, 1, or 2
- Has total bilirubin < 1.5 mg/dL, serum albumin > 3.0 gm/dL, AST and ALT < 1.5 ULN or < 3 x ULN for subjects with known hepatic metastases
- Has serum creatinine < 1.5 × ULN
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- Has hemoglobin ≥ 10 g/dL, ANC ≥ 1.5 × 109/L, and platelet count ≥ 100 × 109/L
- 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
- Has read, understood, and signed the ICF
- Women of childbearing potential must not be pregnant or breast-feeding. In addition, a medically acceptable method of birth control must be used or total abstinence. 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
- 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)
- Gliomas are excluded, as well as any history of brain metastases, seizures or underlying brain injury
- 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 history of blood clots, pulmonary embolism, or DVT unless controlled by anticoagulant treatment
- Has a history of an arterial thromboembolic event within the prior six months including CVA, TIA, MI, or unstable angina
- Has uncontrolled HIV or hepatitis B or C
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- Has any clinically significant infection
- Has any other severe, uncontrolled medical condition, including uncontrolled DM or unstable CHF
- Radiation therapy to more than 25% of the bone marrow
- Prior allogeneic bone marrow or organ transplantation
- > Grade 1 peripheral neuropathy within 14 days before enrollment.
- Patient has received other investigational drugs with 14 days before enrollment
- Other severe acute or chronic medical or psychiatric conditions or laboratory abnormality that may increase the risk associated with study participation
- 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
- 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
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Johns Hopkins Kimmel 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 1
This Phase I dose escalation study will evaluate Procaspase Activating Compound-1 (PAC-1), a small molecule that activates procaspase -3 to caspase-3, resulting in apoptosis of cancer cells, in patients with advanced malignancies. As of March 1, 2019, only patients with neuroendocrine tumors will be enrolled in Component 1 of this study. PAC-1 is taken orally on days 1-21 of a 28-day cycle. The maximum tolerated dose (MTD) of PAC-1 (5 dose levels) will be determined using a modified-Fibonacci dose-escalation 3+3 design. Treatment continues until disease progression, unacceptable toxicity, physician discretion, or patient refusal.
- Being tested
- PAC-1
- Keywords
- refractory, intolerant, solid tumors, PNET, neuroendocrine
- Medical subject headings
- Adenoma, Islet Cell, Neuroendocrine Tumors, Neuroectodermal Tumors, Primitive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PAC-1Drug
Also called Procaspase Activating Compound-1
PAC-1 is taken orally on days 1-21 of a 28-day cycle.
| Study group | Role | What they receive |
|---|---|---|
| Open label | Experimental | Using a dose-escalation design, PAC-1 is administered orally on days 1-21, at the assigned dose, of a 28-day cycle. Receives: Drug: PAC-1 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose
The primary objective of this study component is to determine the maximum tolerated dose (MTD) of PAC-1 in patients with advanced, previously treated malignancy, by evaluation of toxicity and tolerability.
Measured: Up to 30 days post last dose
Secondary outcomes (3)
Adverse Effects
Characterize adverse effects (AE) of PAC-1 in patients with advanced malignancy.
Measured: Up to 30 days post final dose
Disease Response based on RECIST Criteria for patients with solid tumors
Evaluate clinical response of PAC-1 in patients with solid tumors (RECIST v 1.1).
Measured: Up to 8 weeks following final dose
Disease Response based on Deauville PET Criteria for patients with lymphoma
Evaluate clinical response of PAC-1 in patients with lymphoma (Deauville PET Criteria).
Measured: Up to 8 weeks following final dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Feb 2015 (estimated)
- Study startFeb 2015
- Primary completion18 May 2020
- Study completion18 May 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Solid TumorStudies 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
- Masking
- None (open label)
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanquish Oncology, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- University of Illinois Chicago
- Responsible party
- Principal investigator, Oana Danciu, MD, University of Illinois Chicago
- Investigators
- Oana C Danciu, M.D., Principal investigator, University of Illinois Chicago
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02355535
- Sponsor's protocol ID
- 2015-0057
- Status last verified
- Sep 2020
- First submitted
- 30 Jan 2015
- Last updated
- 24 Sep 2020
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Danciu OC, Holdhoff M, Peterson RA, Fischer JH, Liu LC, Wang H, Venepalli NK, Chowdhery R, Nicholas MK, Russell MJ, Fan TM, Hergenrother PJ, Tarasow TM, Dudek AZ. Phase I study of procaspase-activating compound-1 (PAC-1) in the treatment of advanced malignancies. Br J Cancer. 2023 Mar;128(5):783-792. doi: 10.1038/s41416-022-02089-7. Epub 2022 Dec 5.
PubMed 36470974
Study at a glance
From the registry record, last updated by the sponsor on 24 Sep 2020. 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 1
- ClinicalTrials.gov ID
- NCT02355535
- Acronym / sponsor ID
- 2015-0057
- Keywords
- refractory, intolerant, solid tumors, PNET, neuroendocrine
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- Vanquish Oncology, Inc.Industry (pharma, biotech, devices)
- Collaborators
- University of Illinois Chicago
- Study start
- Feb 2015 (actual)
- Primary completion
- 18 May 2020 (actual)
- Study completion
- 18 May 2020 (actual)
- First posted
- 4 Feb 2015 (estimated)
- 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 Phase I dose escalation study will evaluate Procaspase Activating Compound-1 (PAC-1), a small molecule that activates procaspase -3 to caspase-3, resulting in apoptosis of cancer cells, in patients with advanced malignancies. As of March 1, 2019, only patients with neuroendocrine tumors will be enrolled in Component 1 of this study. PAC-1 is taken orally on days 1-21 of a 28-day cycle. The maximum tolerated dose (MTD) of PAC-1 (5 dose levels) will be determined using a modified-Fibonacci dose-escalation 3+3 design. Treatment continues until disease progression, unacceptable toxicity, physician discretion, or patient refusal.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Open label | Experimental | Drug: PAC-1Using a dose-escalation design, PAC-1 is administered orally on days 1-21, at the assigned dose, of a 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 (14 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
- Has measurable disease, defined as at least 1 tumor that fulfills the criteria for a target lesion according to RECIST 1.1, or lymphoma that fulfills the Deauville PET Criteria
- Has an ECOG PS of 0, 1, or 2
- Has total bilirubin < 1.5 mg/dL, serum albumin > 3.0 gm/dL, AST and ALT < 1.5 ULN or < 3 x ULN for subjects with known hepatic metastases
Key exclusion criteria (17 listed)
- Had surgery within 4 weeks prior to study treatment except for minor procedures (hepatic biliary stent placement is allowed)
- Gliomas are excluded, as well as any history of brain metastases, seizures or underlying brain injury
- 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 history of blood clots, pulmonary embolism, or DVT unless controlled by anticoagulant treatment
- Has a history of an arterial thromboembolic event within the prior six months including CVA, TIA, MI, or unstable angina
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-1Also: Procaspase Activating Compound-1PAC-1 is taken orally on days 1-21 of a 28-day cycle. | Drug | Open label |
Primary outcome
Maximum Tolerated Dose
Time frame: Up to 30 days post last dose
The primary objective of this study component is to determine the maximum tolerated dose (MTD) of PAC-1 in patients with advanced, previously treated malignancy, by evaluation of toxicity and tolerability.
3 secondary outcomes
Adverse Effects
Time frame: Up to 30 days post final dose
Disease Response based on RECIST Criteria for patients with solid tumors
Time frame: Up to 8 weeks following final dose
Disease Response based on Deauville PET Criteria for patients with lymphoma
Time frame: Up to 8 weeks following final dose
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Sep 2020.
- Derived from this study: PubMed 36470974Danciu OC, Holdhoff M, Peterson RA, Fischer JH, Liu LC, Wang H, Venepalli NK, Chowdhery R, Nicholas MK, Russell MJ, Fan TM, Hergenrother PJ, Tarasow TM, Dudek AZ. Phase I study of procaspase-activating compound-1 (PAC-1) in the treatment of advanced malignancies. Br J Cancer. 2023 Mar;128(5):783-792. doi: 10.1038/s41416-022-02089-7. Epub 2022 Dec 5.
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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
University of Illinois 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 in people with Solid Tumor and Pancreatic Neuroendocrine Tumor, 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 14 inclusion and 17 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: finished, as of the sponsor's last update on 24 Sep 2020. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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 (time frame: Up to 30 days post last dose). 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 NCT02355535, which also lists 1 linked publication.
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 Sep 2020.