Phase 2/3 Study to Evaluate Efficacy and Safety of Unesbulin in Leiomyosarcoma
Research type
Research Study
Full title
A PHASE 2/3 STUDY TO EVALUATE THE EFFICACY AND SAFETY OF UNESBULIN IN UNRESECTABLE OR METASTATIC, RELAPSED OR REFRACTORY LEIOMYOSARCOMA
IRAS ID
1005169
Contact name
Mona Wahba
Contact email
Sponsor organisation
PTC Therapeutics, Inc.
Eudract number
2022-000073-12
Clinicaltrials.gov Identifier
Research summary
Research Summary - Leiomyosarcoma is a rare soft tissue cancer that spreads through the bloodstream and grows within the smooth muscle, commonly found in the abdomen or uterus. Current treatments are limited and involve surgery or chemotherapy if it is inoperable or has spread to multiple locations.
PTC596-ONC-008-LMS is a phase 2/3 study to test the effectiveness and safety of unesbulin with dacarbazine for patients with relapsed, unresectable disease or unresponsive to current treatments. The study drug, unesbulin is a novel molecule that disrupts an important binding site involved in the tumour cell’s cytoskeletal structure resulting in cell death, slowing the cancer progression. Dacarbazine is a chemotherapeutic agent (anti-cancer drug) that has shown efficacy in this disease population. The preclinical data of unesbulin in combination with dacarbazine has shown more effective tumour suppression than either drug alone.
Approximately 345 participants will be enrolled into this international, multicentre, randomised, double-blind, placebo-controlled study. Eligible participants will have history of previous drug therapy (300 participants with up to 3 and 45 participants with at least 4 systemic therapies). The participants will be randomly divided into two groups in 2:1 ratio: Unesbulin in combination with Dacarbazine and Placebo in combination with Dacarbazine respectively.
The study is designed as 21 day treatment cycles. Participants will be take either the study drug or placebo orally without food twice weekly. Participants in all treatment groups will be administered dacarbazine using an IV once every 21 days. The study period will be approximately 4 years.
The primary objective is to compare progression free survival (length of time during and after treatment without the cancer getting worse) of unesbulin plus dacarbazine versus placebo plus dacarbazine.
The study is sponsored by PTC Therapeutics Inc.
Lay summary - "The main goal of the study was to learn whether adding unesbulin to dacarbazine might treat Leiomyosarcoma (LMS) better than dacarbazine alone (dacarbazine plus the placebo).
All participants who had tried up to 3 other lines of drug therapy before joining this study were included in these results. This included 209 participants who were assigned to receive unesbulin plus dacarbazine and 105 participants who were assigned to receive the placebo
plus dacarbazine.
The main measurement that researchers used in the study to evaluate the treatment effect of unesbulin is called progression-free survival (PFS). PFS is how long a person lives with LMS before it progresses (gets worse).Researchers measured the median PFS in the group of participants who received unesbulin plus dacarbazine. Median is a statistics term. It is the middle value in a set of measurements.
They compared this with the median PFS in the group of participants who received the placebo plus dacarbazine.
The median PFS was:
• 3.6 months for participants who received unesbulin plus dacarbazine
• 2.6 months for participants who received the placebo plus dacarbazine
While the median PFS was longer for the group that received unesbulin, the difference between the 2 groups was not large enough to be considered “clinically meaningful”. This means it was unlikely that unesbulin would have a meaningful impact on the amount of time that a person could live with LMS before it got worse.Researchers also used other (secondary) measurements to evaluate the treatment effect of unesbulin.
These measurements included:
• Overall survival: Overall survival is how long a person lives after starting treatment.
o Because the study was stopped early, researchers did not have enough information to determine and compare median overall survival in the 2 treatment groups.
• Objective response rate: The objective response rate is the percentage of participants whose tumours disappeared completely or shrank in size by a certain amount after starting treatment. There were 294 participants who contributed to this measurement, including 198 who were assigned to receive unesbulin plus dacarbazine and 96 who were assigned to receive the placebo plus dacarbazine.
o The objective response rate was 8.1% among participants who received unesbulin plus dacarbazine (16 of 198 participants).
o The objective response rate was 2.1% among participants who received the placebo plus dacarbazine (2 of 96 participants).
• Duration of response: Among participants whose tumours disappeared or shrank in size after starting treatment, the duration of response is how long this response to treatment lasted before their LMS returned or got worse.
o Because the study was stopped early, researchers did not have enough information to determine and compare the median duration of response in the 2 treatment groups.
• Disease control rate: The disease control rate is the percentage of participants whose tumours disappeared, shrank in size, or remained stable for at least 3 months. There were 294 participants who contributed to this measurement, including 198 who were assigned to receive unesbulin plus dacarbazine and 96 who were assigned to receive the placebo plus dacarbazine.
o The disease control rate was 36.4% among participants who received unesbulin plus dacarbazine (72 of 198 participants).
o The disease control rate was 27.1% among participants who received the placebo plus dacarbazine (26 of 96 participants)."REC name
North East - Newcastle & North Tyneside 2 Research Ethics Committee
REC reference
22/NE/0089
Date of REC Opinion
5 Jul 2022
REC opinion
Further Information Favourable Opinion