Symptoms and General Pathology

All Conditions

Neoplasms

Rare Diseases

Recurrence

Leiomyosarcoma

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Sarcoma

Soft Tissue Sarcoma

Antineoplastic Agents

All Drugs and Chemicals

Dacarbazine

Antineoplastic Agents, Alkylating

Alkylating Agents

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.

Unesbulin will be administered as per the dose and schedule specified in the arm.

Unesbulin

Dacarbazine will be administered as per the dose and schedule specified in the arm.

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.

A Study of Unesbulin (PTC596) in Combination With Dacarbazine in Participants With Advanced Leiomyosarcoma (LMS)

A Phase 1B Study of Unesbulin (PTC596) in Combination With Dacarbazine in Patients With Locally Recurrent, Unresectable or Metastatic Relapsed/Refractory Leiomyosarcoma

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.

Objective Response is defined as confirmed best response of complete response (CR) or partial response (PR).

Time to response is defined as the first time either PR or CR occurs.

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.

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.

Best overall response is defined as CR, PR and stable disease (SD).

OS is defined as the time from the first dose of study drug to the date of death from any cause.

Pharmacokinetic (PK) variables will be calculated from the plasma concentration data using standard compartmental or non-compartmental methods, as appropriate for the data.

PK variables will be calculated from the plasma concentration data using standard compartmental or non-compartmental methods, as appropriate for the data.

PTC Therapeutics

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Carcinoma

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Neoplasms, Glandular and Epithelial

Ovarian Cancer

Ovarian Epithelial Cancer

Paclitaxel

Albumin-Bound Paclitaxel

Carboplatin

Carboplatin AUC 6mg/L IV on day 1; Paclitaxel 175mg/m2 IV on day 1; Unesbulin PO, twice a week, on day 1, 4, 8, 11, 15 and 18 per 21-day cycle for the first 3 cycles.

Unesbulin will be given in combination with carboplatin and paclitaxel for up to 7 cycles depending on which cohort the patient is in.

Kathleen Moore, MD

This is an open-label Phase Ib dose-escalation study to determine the safety, tolerability, and pharmacokinetics of Unesbulin when combined with and following conventional chemotherapy and as maintenance therapy as a capsule (weight based dosing) and a tablet (fixed dosing) in women with epithelial ovarian, fallopian tube or primary peritoneal cancer which is previously untreated.

For all cohorts, the study drug Unesbulin will be orally administered prior to chemotherapy (paclitaxel and carboplatin), twice a week of each 21-day cycle. Chemotherapy will be administered on day 1 of each cycle by vein. Dose escalation levels for Unesbulin will occur per protocol and doses may be de-escalated for management of toxicity. Patients will receive a total of 3 cycles of Unesbulin and chemotherapy. Surgery will be performed within 6 weeks after the last dose of Cycle 3. An additional 3-7 cycles of Unesbulin and chemotherapy (carboplatin and paclitaxel) may be given as maintenance therapy for up to two years at the discretion of the treating physician.

This trial will utilize a traditional 3+ 3 design with dose escalation.

Unesbulin in Women With Ovarian Cancer Receiving Neoadjuvant Chemotherapy

Phase 1B Trial With Unesbulin in High-Grade Serous Ovarian Cancer: a Targeted Approach Toward Chemoresistant Stem-Like Cancer Cells

To determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLTs) of Unesbulin in combination with and following conventional chemotherapy and as maintenance as a capsule (weight-based dosing) and a tablet (fixed dosing). Standard chemotherapy will be comprised of carboplatin and weekly paclitaxel. The DLTs will be based on adverse events that occur during administration of the first 2 cycles of combination Unesbulin and chemotherapy (a cycle = 21 days).

To examine the tolerability of the combination at the MTD of Unesbulinassessed in combination with standard neoadjuvant chemotherapy.

To determine the recommended phase II dose (RP2D) of Unesbulin in combination with standard neoadjuvant chemotherapy.

Evaluate clinical response by measuring serum CA-125. If CA-125 is initially above the upper normal limit, it must normalize for patients to be considered in complete clinical response.

To evaluate pharmacokinetic parameters of Unesbulin in patients with stage III or IV epithelial ovarian, primary peritoneal or fallopian tube cancer receiving neoadjuvant chemotherapy with carboplatin/paclitaxel

The duration of time (one year) that patients are alive and their cancer is progression-free.

The duration of time (two years) that patients are alive and their cancer is progression-free.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of Unesbulin (PTC596) in Combination With Dacarbazine in Participants With Advanced Leiomyosarcoma (LMS)	NCT03761095	Leiomyosarcoma	Unesbulin Dacarbazine	18 Years -	PTC Therapeutics
Unesbulin in Women With Ovarian Cancer Receiving Neoadjuvant Chemotherapy	NCT03206645	Ovarian Cancer	Unesbulin	18 Years - 99 Years	University of Oklahoma
A Study of Unesbulin (PTC596) in Combination With Dacarbazine in Participants With Advanced Leiomyosarcoma (LMS)	NCT03761095	Leiomyosarcoma	Unesbulin Dacarbazine	18 Years -	PTC Therapeutics

Spots Global Cancer Trial Database for unesbulin

Every month we try and update this database with for unesbulin cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for unesbulin

Every month we try and update this database with for unesbulin cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for unesbulin cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.