LeiomyosarcomaPhase 1NCT03761095
A Study of Unesbulin (PTC596) in Combination With Dacarbazine in Participants With Advanced Leiomyosarcoma (LMS)
A Phase 1 study testing Unesbulin and Dacarbazine in people with Leiomyosarcoma, run by PTC Therapeutics at 4 sites in United States.
Trial summary
The primary objective of this study is to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of unesbulin in combination with dacarbazine for the treatment of advanced LMS and determine the overall safety profile of unesbulin in combination with dacarbazine. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Leiomyosarcoma
- What is being tested?
- Unesbulin and Dacarbazine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 41 participants
- Where
- 4 sitesUnited States
- Study dates
- 13 Mar 2019to 5 Feb 2024
- 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
- Signed consent of an Institutional Review Board (IRB)-approved informed consent form (ICF) and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information (if appropriate).
- Willingness and ability to comply with scheduled visits, drug administration plan, laboratory tests, other study procedures, and study restrictions.
- Disease Status including all of the following:
- Histological or cytological confirmation of LMS arising at any anatomic site.
- Advanced (metastatic) or locally advanced unresectable disease.
- Ineligible for other high-priority national or institutional study.
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- Measurable disease per RECIST v1.1 criteria.
- Demographics:
- Age greater than or equal to (>/=) 18
- Male and Female
- Performance Status:
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
- Hematopoietic:
- Absolute neutrophil count (ANC) count >/= 1,500/cubic millimeters (mm^3) without the use of growth factors in the past 7 days;
- Platelet count >=100,000/mm^3 without platelet transfusion in the past 5 days;
- Hemoglobin >=9 grams per deciliter (g/dL) (packed red blood cell transfusion is allowed).
- Hepatic:
- Bilirubin lesser than (<) upper limit of normal (ULN);
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) <1.5 times ULN;
- Participants with liver metastases may be enrolled.
- Pulmonary:
- Participants with well-controlled asthma (for example Use of rescue medications <2 times/week over the last 12 months) or Chronis Obstructive Pulmonary Disease (COPD) (for example no exacerbations over the prior 3 months) may be enrolled.
- Renal:
- Creatinine <1.5 times normal, or creatinine clearance greater than (>) 45 milliliters per minute (mL/min).
- Prior Therapies:
- Toxicity from prior therapies recovered to Grade lesser than or equal to (<=) 1 or participant's baseline, except for alopecia. In addition, endocrinopathies associated with prior immunotherapy based treatments which are well controlled on replacement medication are not exclusionary
- Chemotherapy:
- Up to and inclusive of 4 prior systemic cytotoxic oncology therapy regimens for metastatic, locally recurrent, or unresectable LMS, with the last dose of prior therapy administered no fewer than 30 days or 5 times the drug half-life prior to screening. Note: prior treatment with non-cytotoxic therapy regimens (for example targeted therapies, hormonal therapies, or tyrosine kinase inhibitors) are not considered cytotoxic oncology therapies.
- Surgery:
- At least 4 weeks since prior surgery and recovered in opinion of investigator.
- Other:
- Capable of swallowing oral medication.
- Females of childbearing potential must have a negative pregnancy test within 7 days prior to being registered for protocol therapy.
- Males and females of childbearing potential must be willing to use an effective method of contraception (hormonal or barrier method of birth control; abstinence) from the time consent is signed until 90 days after treatment discontinuation. Note: The Definition of effective contraception will be based on the judgement of the Principal Investigator (PI) or Designee.
Who cannot join
- Participants meeting any of the following criteria will not be eligible for enrollment:
- Received any systemic anticancer therapy including investigational agents <=3 weeks prior to initiation of study treatment. Additionally, Participants may have not received radiation </= 3 weeks prior to initiation of study treatment.
- Co-existing active infection or any co-existing medical condition likely to interfere with study procedures, including:
- Significant cardiovascular disease (New York Heart Association Class III or IV cardiac disease), myocardial infarction within the past 6 months, unstable angina, congestive heart failure requiring therapy, unstable arrhythmia or a need for anti-arrhythmic therapy, or evidence of ischemia on electrocardiogram (ECG), marked baseline prolongation of QT/QTc (corrected QT interval) interval, for example, repeated demonstration of a QTc interval >500 milliseconds (msec) (Long QT Syndrome [congenital]).
- Known human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) positivity.
- History of solid organ transplantation.
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- Therapeutics:
- Known or suspected allergy or immediate or delayed hypersensitivity to unesbulin or dacarbazine or any agent given in this study.
- Gastrointestinal:
- Bowel obstruction, malabsorption, or other contraindication to oral medication.
- Gastrointestinal disease or other condition that could affect absorption.
- Active peptic ulcer disease.
- Inflammatory bowel disease (including ulcerative colitis and Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis.
- Any condition that impairs participant's ability to swallow oral medications.
- Wounds /Surgery:
- Serious non-healing wound, ulcer, or bone fractures.
- Major surgery, open biopsy or significant traumatic injury which has not recovered in the opinion of the investigator, within 28 days of baseline.
- Mucosal or internal bleeding.
- Concomitant Medications:
- Concomitant strong CYP1A2 inhibitors (like selective serotonin reuptake inhibitor [SSRI] agents fluvoxamine and fluoxetine) should be avoided. CYP1A2 inhibitors may inhibit the conversion of dacarbazine to its active metabolite and may increase the exposure of unesbulin.
- Other:
- Prior malignancies other than LMS, that required treatment or have shown evidence of recurrence (except for non-melanoma skin cancer or adequately treated cervical carcinoma in situ) during the 5 years prior to initiation. Cancer treated with curative intent more than 5 years previously and without evidence of recurrence is not an exclusion.
- Known coagulopathy or bleeding diathesis. Participants on anti-coagulation should be monitored closely and International Normalized Ratio (INR) within normal range.
- Prior or ongoing clinically significant illness, medical or psychiatric condition, medical history, physical findings, ECG findings, or laboratory abnormality that, in the investigator's opinion, could affect the safety of the participant, or alter the absorption, distribution, metabolism, or excretion of the study drugs, or could impair the assessment of study results.
- History of brain metastases or leptomeningeal disease at any time in participant's history, including treated central nervous system (CNS) disease which is clinically and radiographically stable.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
John Hopkins
Baltimore, Maryland, 21287
Mayo Clinic Florida
Jacksonville, Florida, 32204
Columbia University Medical Center
New York, New York, 10032
Washington University Medical Campus
St Louis, Missouri, 63110
About this study
Official title: A Phase 1B Study of Unesbulin (PTC596) in Combination With Dacarbazine in Patients With Locally Recurrent, Unresectable or Metastatic Relapsed/Refractory Leiomyosarcoma
The primary objective of this study is to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of unesbulin in combination with dacarbazine for the treatment of advanced LMS and determine the overall safety profile of unesbulin in combination with dacarbazine.
This study will employ the time-to-event continual reassessment method (TITE-CRM) for dose finding. Treatment will be initiated at dose level 2 (DL2) (Dacarbazine 1000 milligrams per square meter [mg/m^2] intravenously [IV] every 21 days in combination with unesbulin 200 milligrams [mg] orally twice weekly) for the first participant. This dose level represents the investigator's best assessment of the MTD based on available toxicity data for both agents. For subsequent participants, the dose level at which treatment is initiated will be selected based on the TITE-CRM using the most up to date dose-limiting toxicity (DLT) information from all participants previously treated. To enroll additional participants at the RP2D, the study is amended to include an expansion cohort of up to 12 participants (some of whom could be ongoing participants who reconsent).
Treatment will continue for each participant until evidence of unacceptable toxicity, disease progression, or treatment discontinuation for another reason.
- Conditions
- Leiomyosarcoma
- Being tested
- Unesbulin, Dacarbazine
- Medical subject headings
- Leiomyosarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
UnesbulinDrug
Also called PTC596
Unesbulin will be administered as per the dose and schedule specified in the arm.
DacarbazineDrug
Also called DTIC
Dacarbazine will be administered as per the dose and schedule specified in the arm.
| Study group | Role | What they receive |
|---|---|---|
| Unesbulin and Dacarbazine | Experimental | Participants will receive unesbulin orally twice weekly in combination with dacarbazine IV once every 21 days. The first participant will receive dacarbazine 1000 mg/m^2 IV every 21 days in combination with unesbulin 200 mg tablet orally twice weekly. For subsequent participants, the dose level at which treatment is initiated will be selected based on the TITE-CRM using the most up to date dose DLT information from all participants previously treated. Participants will receive unesbulin 300 mg twice weekly in combination with dacarbazine in the expansion cohort. Treatment will continue for each participant until evidence of unacceptable toxicity, disease progression, or treatment discontinuation for another reason. Receives: Drug: Unesbulin; Drug: Dacarbazine |
What is being measured
The primary outcome is the main question the study is designed to answer.
MTD and RP2D of Unesbulin in Combination With Dacarbazine
MTD will be determined using the TITE-CRM for dose-finding. MTD is defined as the dose associated with a target probability of DLT of 0.25.
Measured: First 2 cycles of treatment (6 weeks)
Number of Participants With Adverse Events
Measured: From screening until end of study (up to approximately 1.5 years)
Secondary outcomes (13)
Objective Response Rate (ORR) (Percentage of Participants With Objective Response) as Determined by the Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
Objective Response is defined as confirmed best response of complete response (CR) or partial response (PR).
Measured: From Baseline until the date of objectively documented progression per RECIST v1.1 or the date of initiation of subsequent therapy or palliative local therapy, whichever occurs first (up to approximately 1.5 years)
Time to Response as Determined by the Investigator Using RECIST v1.1
Time to response is defined as the first time either PR or CR occurs.
Measured: From Baseline until the date of first occurrence of CR or PR (up to approximately 1.5 years)
Duration of Response (DOR)
DOR is defined as the time from the date of first confirmed response to the date of the first documented tumor progression (per RECIST v1.1) or death due to any cause, whichever occurs first.
Measured: Time from the date of first confirmed response to the date of the first documented tumor progression or death due to any cause, whichever occurs first (up to approximately 1.5 years)
Progression-Free Survival (PFS)
PFS is defined as the time from the first dose of study drug to the date of the first documented tumor progression as determined by the investigator using RECIST v1.1 or death due to any cause, whichever occurs first.
Measured: Time from the first dose of study drug to the date of the first documented tumor progression or death due to any cause, whichever occurs first (up to approximately 1.5 years)
Best Overall Response Rate (Disease Control Rate) (Percentage of Participants With Best Overall Response)
Best overall response is defined as CR, PR and stable disease (SD).
Measured: From Baseline until the date of objectively documented progression per RECIST v1.1 or the date of initiation of subsequent therapy or palliative local therapy, whichever occurs first (up to approximately 1.5 years)
Overall Survival (OS)
OS is defined as the time from the first dose of study drug to the date of death from any cause.
Measured: Time from the first dose of study drug to the date of death from any cause (up to approximately 1.5 years)
Maximum Observed Plasma Concentration (Cmax) of Unesbulin, Dacarbazine, and Inactive Metabolite of Dacarbazine (5-amino-imidazole-4-carboxamide [AIC])
Pharmacokinetic (PK) variables will be calculated from the plasma concentration data using standard compartmental or non-compartmental methods, as appropriate for the data.
Measured: Unesbulin: Predose (within 1 hour [hr]); 1,2,3 to 824, 48, 72 hrs postdose (during any cycle); Dacarbazine and AIC: Predose (within 1 hr); 0.5,1 hr post start of infusion; 0.25,0.5,1,3,7,23 hrs postdose on Cycle 1 Day 1,Cycle 2 Day 1 (each cycle=21 days)
Time to Reach Maximum Plasma Concentration (Tmax) of Unesbulin, Dacarbazine, and Inactive Metabolite of Dacarbazine (AIC)
PK variables will be calculated from the plasma concentration data using standard compartmental or non-compartmental methods, as appropriate for the data.
Measured: Unesbulin: Predose (within 1 hr); 1,2,3 to 824, 48, 72 hrs postdose (during any cycle); Dacarbazine and AIC: Predose (within 1 hr); 0.5,1 hr post start of infusion; 0.25,0.5,1,3,7,23 hrs postdose on Cycle 1 Day 1,Cycle 2 Day 1 (each cycle=21 days)
Area Under the Plasma Concentration-Time Curve (AUC) of Unesbulin, Dacarbazine, and Inactive Metabolite of Dacarbazine (AIC)
PK variables will be calculated from the plasma concentration data using standard compartmental or non-compartmental methods, as appropriate for the data.
Measured: Unesbulin: Predose (within 1 hr); 1,2,3 to 824, 48, 72 hrs postdose (during any cycle); Dacarbazine and AIC: Predose (within 1 hr); 0.5,1 hr post start of infusion; 0.25,0.5,1,3,7,23 hrs postdose on Cycle 1 Day 1, Cycle 2 Day 1 (each cycle=21 days)
Half-Life (t1/2) of Unesbulin, Dacarbazine, and Inactive Metabolite of Dacarbazine (AIC)
PK variables will be calculated from the plasma concentration data using standard compartmental or non-compartmental methods, as appropriate for the data.
Measured: Unesbulin: Predose (within 1 hr); 1,2,3 to 824, 48, 72 hrs postdose (during any cycle); Dacarbazine and AIC: Predose (within 1 hr); 0.5,1 hr post start of infusion; 0.25,0.5,1,3,7,23 hrs postdose on Cycle 1 Day 1, Cycle 2 Day 1 (each cycle=21 days)
Apparent Clearance (CL/F) of Unesbulin, Dacarbazine, and Inactive Metabolite of Dacarbazine (AIC)
PK variables will be calculated from the plasma concentration data using standard compartmental or non-compartmental methods, as appropriate for the data.
Measured: Unesbulin: Predose (within 1 hr); 1,2,3 to 824, 48, 72 hrs postdose (during any cycle); Dacarbazine and AIC: Predose (within 1 hr); 0.5,1 hr post start of infusion; 0.25,0.5,1,3,7,23 hrs postdose on Cycle 1 Day 1, Cycle 2 Day 1 (each cycle=21 days)
Apparent Volume of Distribution (Vz/F) of Unesbulin, Dacarbazine, and Inactive Metabolite of Dacarbazine (AIC)
PK variables will be calculated from the plasma concentration data using standard compartmental or non-compartmental methods, as appropriate for the data.
Measured: Unesbulin: Predose (within 1 hr); 1,2,3 to 824, 48, 72 hrs postdose (during any cycle); Dacarbazine and AIC: Predose (within 1 hr); 0.5,1 hr post start of infusion; 0.25,0.5,1,3,7,23 hrs postdose on Cycle 1 Day 1, Cycle 2 Day 1 (each cycle=21 days)
Accumulation Ratio (R) of Unesbulin, Dacarbazine, and Inactive Metabolite of Dacarbazine (AIC)
PK variables will be calculated from the plasma concentration data using standard compartmental or non-compartmental methods, as appropriate for the data.
Measured: Unesbulin: Predose (within 1 hr); 1,2,3 to 824, 48, 72 hrs postdose (during any cycle); Dacarbazine and AIC: Predose (within 1 hr); 0.5,1 hr post start of infusion; 0.25,0.5,1,3,7,23 hrs postdose on Cycle 1 Day 1, Cycle 2 Day 1 (each cycle=21 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Dec 2018
- Study start13 Mar 2019
- Primary completion5 Feb 2024
- Study completion5 Feb 2024
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 LeiomyosarcomaStudies 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
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- PTC Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03761095
- Sponsor's protocol ID
- PTC596-ONC-007-LMS
- Status last verified
- Feb 2024
- First submitted
- 29 Nov 2018
- Last updated
- 15 Mar 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Van Tine BA, Ingham MA, Attia S, Meyer CF, Baird JD, Brooks-Asplund E, D'Silva D, Kong R, Mwatha A, O'Keefe K, Weetall M, Spiegel R, Schwartz GK. Phase Ib Study of Unesbulin (PTC596) Plus Dacarbazine for the Treatment of Locally Recurrent, Unresectable or Metastatic, Relapsed or Refractory Leiomyosarcoma. J Clin Oncol. 2024 Jul 10;42(20):2404-2414. doi: 10.1200/JCO.23.01684. Epub 2024 Apr 29.
PubMed 38684039
Study at a glance
From the registry record, last updated by the sponsor on 15 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1B Study of Unesbulin (PTC596) in Combination With Dacarbazine in Patients With Locally Recurrent, Unresectable or Metastatic Relapsed/Refractory Leiomyosarcoma
- ClinicalTrials.gov ID
- NCT03761095
- Acronym / sponsor ID
- PTC596-ONC-007-LMS
- Conditions
- Leiomyosarcoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 41 participants (actual)
- Lead sponsor
- PTC TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 13 Mar 2019 (actual)
- Primary completion
- 5 Feb 2024 (actual)
- Study completion
- 5 Feb 2024 (actual)
- First posted
- 3 Dec 2018 (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 objective of this study is to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of unesbulin in combination with dacarbazine for the treatment of advanced LMS and determine the overall safety profile of unesbulin in combination with dacarbazine.
This study will employ the time-to-event continual reassessment method (TITE-CRM) for dose finding. Treatment will be initiated at dose level 2 (DL2) (Dacarbazine 1000 milligrams per square meter [mg/m^2] intravenously [IV] every 21 days in combination with unesbulin 200 milligrams [mg] orally twice weekly) for the first participant. This dose level represents the investigator's best assessment of the MTD based on available toxicity data for both agents. For subsequent participants, the dose level at which treatment is initiated will be selected based on the TITE-CRM using the most up to date dose-limiting toxicity (DLT) information from all participants previously treated. To enroll additional participants at the RP2D, the study is amended to include an expansion cohort of up to 12 participants (some of whom could be ongoing participants who reconsent).
Treatment will continue for each participant until evidence of unacceptable toxicity, disease progression, or treatment discontinuation for another reason.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Unesbulin and Dacarbazine | Experimental | Drug: Unesbulin, Drug: DacarbazineParticipants will receive unesbulin orally twice weekly in combination with dacarbazine IV once every 21 days. The first participant will receive dacarbazine 1000 mg/m^2 IV every 21 days in combination with unesbulin 200 mg tablet orally twice weekly. For subsequent participants, the dose level at which treatment is initiated will be selected based on the TITE-CRM using the most up to date dose DLT information from all participants previously treated. Participants will receive unesbulin 300 mg twice weekly in combination with dacarbazine in the expansion cohort. Treatment will continue for each participant until evidence of unacceptable toxicity, disease progression, or treatment discontinuation for another reason. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (34 listed)
- Signed consent of an Institutional Review Board (IRB)-approved informed consent form (ICF) and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information (if appropriate).
- Willingness and ability to comply with scheduled visits, drug administration plan, laboratory tests, other study procedures, and study restrictions.
- Disease Status including all of the following:
- Age greater than or equal to (>/=) 18
- Male and Female
Key exclusion criteria (25 listed)
- Received any systemic anticancer therapy including investigational agents <=3 weeks prior to initiation of study treatment. Additionally, Participants may have not received radiation </= 3 weeks prior to initiation of study treatment.
- Co-existing active infection or any co-existing medical condition likely to interfere with study procedures, including:
- Known human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) positivity.
- History of solid organ transplantation.
- Known or suspected allergy or immediate or delayed hypersensitivity to unesbulin or dacarbazine or any agent given in this study.
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 |
|---|---|---|
| UnesbulinAlso: PTC596Unesbulin will be administered as per the dose and schedule specified in the arm. | Drug | Unesbulin and Dacarbazine |
| DacarbazineAlso: DTICDacarbazine will be administered as per the dose and schedule specified in the arm. | Drug | Unesbulin and Dacarbazine |
Primary outcome
MTD and RP2D of Unesbulin in Combination With Dacarbazine
Time frame: First 2 cycles of treatment (6 weeks)
MTD will be determined using the TITE-CRM for dose-finding. MTD is defined as the dose associated with a target probability of DLT of 0.25.
Number of Participants With Adverse Events
Time frame: From screening until end of study (up to approximately 1.5 years)
13 secondary outcomes
Objective Response Rate (ORR) (Percentage of Participants With Objective Response) as Determined by the Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
Time frame: From Baseline until the date of objectively documented progression per RECIST v1.1 or the date of initiation of subsequent therapy or palliative local therapy, whichever occurs first (up to approximately 1.5 years)
Time to Response as Determined by the Investigator Using RECIST v1.1
Time frame: From Baseline until the date of first occurrence of CR or PR (up to approximately 1.5 years)
Duration of Response (DOR)
Time frame: Time from the date of first confirmed response to the date of the first documented tumor progression or death due to any cause, whichever occurs first (up to approximately 1.5 years)
Progression-Free Survival (PFS)
Time frame: Time from the first dose of study drug to the date of the first documented tumor progression or death due to any cause, whichever occurs first (up to approximately 1.5 years)
Best Overall Response Rate (Disease Control Rate) (Percentage of Participants With Best Overall Response)
Time frame: From Baseline until the date of objectively documented progression per RECIST v1.1 or the date of initiation of subsequent therapy or palliative local therapy, whichever occurs first (up to approximately 1.5 years)
Overall Survival (OS)
Time frame: Time from the first dose of study drug to the date of death from any cause (up to approximately 1.5 years)
Maximum Observed Plasma Concentration (Cmax) of Unesbulin, Dacarbazine, and Inactive Metabolite of Dacarbazine (5-amino-imidazole-4-carboxamide [AIC])
Time frame: Unesbulin: Predose (within 1 hour [hr]); 1,2,3 to 824, 48, 72 hrs postdose (during any cycle); Dacarbazine and AIC: Predose (within 1 hr); 0.5,1 hr post start of infusion; 0.25,0.5,1,3,7,23 hrs postdose on Cycle 1 Day 1,Cycle 2 Day 1 (each cycle=21 days)
Time to Reach Maximum Plasma Concentration (Tmax) of Unesbulin, Dacarbazine, and Inactive Metabolite of Dacarbazine (AIC)
Time frame: Unesbulin: Predose (within 1 hr); 1,2,3 to 824, 48, 72 hrs postdose (during any cycle); Dacarbazine and AIC: Predose (within 1 hr); 0.5,1 hr post start of infusion; 0.25,0.5,1,3,7,23 hrs postdose on Cycle 1 Day 1,Cycle 2 Day 1 (each cycle=21 days)
Area Under the Plasma Concentration-Time Curve (AUC) of Unesbulin, Dacarbazine, and Inactive Metabolite of Dacarbazine (AIC)
Time frame: Unesbulin: Predose (within 1 hr); 1,2,3 to 824, 48, 72 hrs postdose (during any cycle); Dacarbazine and AIC: Predose (within 1 hr); 0.5,1 hr post start of infusion; 0.25,0.5,1,3,7,23 hrs postdose on Cycle 1 Day 1, Cycle 2 Day 1 (each cycle=21 days)
Half-Life (t1/2) of Unesbulin, Dacarbazine, and Inactive Metabolite of Dacarbazine (AIC)
Time frame: Unesbulin: Predose (within 1 hr); 1,2,3 to 824, 48, 72 hrs postdose (during any cycle); Dacarbazine and AIC: Predose (within 1 hr); 0.5,1 hr post start of infusion; 0.25,0.5,1,3,7,23 hrs postdose on Cycle 1 Day 1, Cycle 2 Day 1 (each cycle=21 days)
Apparent Clearance (CL/F) of Unesbulin, Dacarbazine, and Inactive Metabolite of Dacarbazine (AIC)
Time frame: Unesbulin: Predose (within 1 hr); 1,2,3 to 824, 48, 72 hrs postdose (during any cycle); Dacarbazine and AIC: Predose (within 1 hr); 0.5,1 hr post start of infusion; 0.25,0.5,1,3,7,23 hrs postdose on Cycle 1 Day 1, Cycle 2 Day 1 (each cycle=21 days)
Apparent Volume of Distribution (Vz/F) of Unesbulin, Dacarbazine, and Inactive Metabolite of Dacarbazine (AIC)
Time frame: Unesbulin: Predose (within 1 hr); 1,2,3 to 824, 48, 72 hrs postdose (during any cycle); Dacarbazine and AIC: Predose (within 1 hr); 0.5,1 hr post start of infusion; 0.25,0.5,1,3,7,23 hrs postdose on Cycle 1 Day 1, Cycle 2 Day 1 (each cycle=21 days)
Accumulation Ratio (R) of Unesbulin, Dacarbazine, and Inactive Metabolite of Dacarbazine (AIC)
Time frame: Unesbulin: Predose (within 1 hr); 1,2,3 to 824, 48, 72 hrs postdose (during any cycle); Dacarbazine and AIC: Predose (within 1 hr); 0.5,1 hr post start of infusion; 0.25,0.5,1,3,7,23 hrs postdose on Cycle 1 Day 1, Cycle 2 Day 1 (each cycle=21 days)
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 15 Mar 2024.
- Derived from this study: PubMed 38684039Van Tine BA, Ingham MA, Attia S, Meyer CF, Baird JD, Brooks-Asplund E, D'Silva D, Kong R, Mwatha A, O'Keefe K, Weetall M, Spiegel R, Schwartz GK. Phase Ib Study of Unesbulin (PTC596) Plus Dacarbazine for the Treatment of Locally Recurrent, Unresectable or Metastatic, Relapsed or Refractory Leiomyosarcoma. J Clin Oncol. 2024 Jul 10;42(20):2404-2414. doi: 10.1200/JCO.23.01684. Epub 2024 Apr 29.
- Related InfoLink provided by the sponsor.
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Rare Disorders, Undiagnosed Disorders
Active, not recruitingPhase 1
A Phase I Trial of Combination Gemcitabine and Nab-Sirolimus in Advanced Leiomyosarcomas or Advanced Soft-Tissue Sarcomas With TSC2 or TSC1 Loss-of-function Mutations or Deletions
Leiomyosarcoma, Soft-tissue Sarcomas
RecruitingPhase 2
A Study of Ivonescimab in People With Leiomyosarcoma
Leiomyosarcoma
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.
The record lists no contact. Use the official record to reach the sponsor.
4 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 Unesbulin and Dacarbazine in people with Leiomyosarcoma, run by PTC Therapeutics at 4 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 34 inclusion and 25 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 15 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 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?
MTD and RP2D of Unesbulin in Combination With Dacarbazine (time frame: First 2 cycles of treatment (6 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?
On the ClinicalTrials.gov record for NCT03761095, 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 15 Mar 2024.