Phase I Study Compound 451238 and Radiotherapy in Soft-tissue Sarcoma
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|ClinicalTrials.gov Identifier: NCT03602833|
Recruitment Status : Recruiting
First Posted : July 27, 2018
Last Update Posted : January 11, 2019
|Condition or disease||Intervention/treatment||Phase|
|Soft-tissue Sarcoma||Drug: Compound 451238||Phase 1 Phase 2|
Overall Study Design
This is a single centre open label, non-randomized, non-placebo phase 1 clinical trial to establish the safety and tolerability compound 451238 in combination with radiotherapy in patients with soft tissue sarcomas (STS). STS patients receiving radiotherapy to a tumour deposit above the diaphragm in the thorax, trunk or extremity, will receive radiotherapy. This study will recruit 12 patients and run as a fixed dose trial. Patients will continue on the treatment regimen unless they progress, suffer unacceptable toxicities, or withdraw from the trial.
A maximum of 12 patients will be recruited. The safety and tolerabilty will be assessed in the first 3+3 patients with expansion to 12 patients as tolerated. A minimum gap of 2 weeks will be left between treatment of the first and second patient (with the combination of RT) to mitigate against multiple patients suffering acute toxicity. Patients will be followed for a minimum of 11 weeks from the initiation of radiotherapy with combined compound 451238 for the purposes of acute toxicity monitoring. Late toxicity monitoring will commence from 11 weeks + one day from initiation of radiotherapy with combined compound 451238 and continue until disease progression or initiation of new anti-cancer therapy.
Safety Follow-up - 30 Days
All patients will be required to attend a safety follow-up visit 30 days after the last dose of compound 451238 or before the initiation of a new anti-cancer treatment, whichever comes first.
Extended Safety Follow-up - 90 Days
Given the potential risk for delayed toxicities, an extended safety follow-up visit must be performed up to 90 days after the last dose of compound 451238 administration. The extended safety follow-up will be performed either via a site visit or via a telephone call with subsequent site visit requested in case any concerns noted during the telephone call. All AEs and SAEs that occur prior to the safety follow-up visit should be reported as described in the trial protocol. After the safety follow-up any unresolved AEs at the patient's last visit should be followed up for as long as medically indicated, but without further recording in the CRF.
Patients who discontinue trial treatment for any reason other than disease progression will move into the follow-up phase and will be assessed every 12 weeks by MRI or radiologic imaging to monitor disease status. Every effort will be made to collect information regarding disease status until the start of new anti-cancer therapy, disease progression, death, withdrawal or end of the study. Information regarding post-study anticancer treatment will be collected if new treatment is initiated.
Once a patient experiences confirmed PD or starts a new anti-cancer therapy, the patient moves into the survival follow-up phase and will be followed up every 12 weeks to determine their disease status. This will be done by reviewing their medical notes and/or contacting the patient and/or General Practitioner directly. Patients will remain on this follow-up until death, withdrawal of consent, or the end of the study, whichever occurs first.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||12 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Compound 451238 and Radiotherapy in Soft-tissue Sarcoma|
|Actual Study Start Date :||November 5, 2018|
|Estimated Primary Completion Date :||February 13, 2020|
|Estimated Study Completion Date :||February 13, 2022|
Experimental: Compound 451238
To assess the safety and tolerability of combining radiotherapy with compound 451238, treating advanced STS.
Drug: Compound 451238
Each patient will receive compound 451238 until disease progression unacceptable toxicities.
- Determine the safety and tolerability of compound 451238 in combination with radiation therapy in patients with soft-tissue sarcoma as assessed by CTCAE v4.0 at 11 weeks from the start of radiotherapy. [ Time Frame: 2 years ]
To assess the safety and tolerability of combining radiotherapy with compound 451238 as evidenced by the rate of occurrence of dose limiting toxicities assessed using CTCAE v4.0.
- Evaluate local control (LC) [ Time Frame: 3 months ]To measure the local control (LC) at 3 months.
- To determine progression free survival (PFS) [ Time Frame: 1 Year ]To measure progression free survival (PFS) at 6 months and 1 year.
- To determine overall survival (OS) [ Time Frame: 1 Year ]To measure overall survival (OS) at 6 months and 1 year.
- To determine acute toxicity [ Time Frame: 11 weeks ]Measure acute ≥ grade 2 toxicity from initiation of radiotherapy and compound 451238 up to 11 weeks following initiation of combined radiotherapy and compound 451238.
- To determine late toxicity [ Time Frame: 11 weeks plus one day until disease progression ]Measure late ≥ grade 2 toxicity from 11 weeks plus one day after initiation of combined radiotherapy and compound 451238 up to confirmed disease progression or initiation of new anti-cancer treatment therapy.
- To measure progression free survival (PFS) in PD-L1 positive population at 6 months and 1 year. [ Time Frame: 1 year ]To evaluate progression free survival (PFS) in a PD-L1 positive population.
- To measure overall survival (OS) in PD-L1 positive population at 6 months and 1 year. [ Time Frame: 1 year ]To evaluate overall survival (OS) in a PD-L1 positive population.
- To evaluate the extent of abscopal effect on local and distant metastasis when compound 451238 and RT are combined. [ Time Frame: 2 years ]To assess for evidence of abscopal response using change in value of selected immunological biomarkers.
- Identification of immunological biomarkers that correlate with response to therapy. [ Time Frame: 2 years Description: To evaluate whether radiation therapy combined with compound 451238results in a measurable change in anti-tumour immunity. ]To evaluate which immunological biomarkers best predict measurable anti-tumour response to radiation therapy combined with compound 451238.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03602833
|Contact: Jeane Guevarafirstname.lastname@example.org|
|Contact: Linda Wedlake||+442089156767||Linda.Wedlake@rmh.nhs.uk|
|The Royal Marsden NHS Foundation Trust||Recruiting|
|London, United Kingdom, SW3 6JJ|
|Contact: Shane Zaidi, MRCP FRCR 02078082591 email@example.com|
|Principal Investigator:||Shane Zaidi||MRCP FRCR|