A randomized phase II study of SM‐88 plus methoxsalen, phenytoin, and sirolimus in patients with metastatic pancreatic cancer treated in the second line and beyond
Abstract Background This trial explores SM‐88 used with methoxsalen, phenytoin, and sirolimus (MPS) in pretreated metastatic pancreatic ductal adenocarcinoma (mPDAC) Methods Forty‐nine patients were randomized to daily 460 or 920 mg oral SM‐88 with MPS (SM‐88 Regimen). The primary endpoint was objec...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-11-01
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| Series: | Cancer Medicine |
| Online Access: | https://doi.org/10.1002/cam4.4768 |
| _version_ | 1811189196005572608 |
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| author | Marcus S. Noel Semmie Kim Marion L. Hartley Steve Wong Vincent J. Picozzi Harry Staszewski Dae Won Kim Jan M. Van Tornout Philip Agop Philip Vincent Chung Allyson J. Ocean Andrea Wang‐Gillam |
| author_facet | Marcus S. Noel Semmie Kim Marion L. Hartley Steve Wong Vincent J. Picozzi Harry Staszewski Dae Won Kim Jan M. Van Tornout Philip Agop Philip Vincent Chung Allyson J. Ocean Andrea Wang‐Gillam |
| author_sort | Marcus S. Noel |
| collection | DOAJ |
| description | Abstract Background This trial explores SM‐88 used with methoxsalen, phenytoin, and sirolimus (MPS) in pretreated metastatic pancreatic ductal adenocarcinoma (mPDAC) Methods Forty‐nine patients were randomized to daily 460 or 920 mg oral SM‐88 with MPS (SM‐88 Regimen). The primary endpoint was objective response rate (RECIST 1.1). Results Thirty‐seven patients completed ≥ one cycle of SM‐88 Regimen (response evaluable population). Disease control rate (DCR), overall survival (OS), and progression‐free survival (PFS) did not differ significantly between dose levels. Stable disease was achieved in 9/37 patients (DCR, 24.3%); there were no complete or partial responses. Quality‐of‐life (QOL) was maintained and trended in favor of 920 mg. SM‐88 Regimen was well tolerated; a single patient (1/49) had related grade 3 and 4 adverse events, which later resolved. In the intention‐to‐treat population of 49 patients, the median overall survival (mOS) was 3.4 months (95% CI: 2.7–4.9 months). Those treated in the second line had an mOS of 8.1 months and a median PFS of 3.8 months. Survival was higher for patients with stable versus progressive disease (any line; mOS: 10.6 months vs. 3.9 months; p = 0.01). Conclusions SM‐88 Regimen has a favorable safety profile with encouraging QOL effects, disease control, and survival trends. This regimen should be explored in the second‐line treatment of patients with mPDAC. ClinicalTrials.gov Identifier: NCT03512756. |
| first_indexed | 2024-04-11T14:31:53Z |
| format | Article |
| id | doaj.art-566d5c8953714e0c95e07051f157b1d7 |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-04-11T14:31:53Z |
| publishDate | 2022-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-566d5c8953714e0c95e07051f157b1d72022-12-22T04:18:33ZengWileyCancer Medicine2045-76342022-11-0111224169418110.1002/cam4.4768A randomized phase II study of SM‐88 plus methoxsalen, phenytoin, and sirolimus in patients with metastatic pancreatic cancer treated in the second line and beyondMarcus S. Noel0Semmie Kim1Marion L. Hartley2Steve Wong3Vincent J. Picozzi4Harry Staszewski5Dae Won Kim6Jan M. Van Tornout7Philip Agop Philip8Vincent Chung9Allyson J. Ocean10Andrea Wang‐Gillam11Georgetown Lombardi Comprehensive Cancer Center Washington District of Columbia USATYME Technologies Inc. Bedminster New Jersey USAThe Ruesch Center for the Cure of Gastrointestinal Cancers Washington District of Columbia USASarcoma Oncology Research Center Santa Monica California USAVirginia Mason Hospital and Medical Center Seattle Washington USAMather Hospital Port Jefferson New York USAThe University of Texas MD Anderson Cancer Center Houston Texas USATYME Technologies Inc. Bedminster New Jersey USAKarmanos Cancer Center Wayne State University Michigan Detroit USACity of Hope Duarte California USAWeill Cornell Medicine New York‐Presbyterian Hospital New York New York USAWashington University School of Medicine in St. Louis St. Louis Missouri USAAbstract Background This trial explores SM‐88 used with methoxsalen, phenytoin, and sirolimus (MPS) in pretreated metastatic pancreatic ductal adenocarcinoma (mPDAC) Methods Forty‐nine patients were randomized to daily 460 or 920 mg oral SM‐88 with MPS (SM‐88 Regimen). The primary endpoint was objective response rate (RECIST 1.1). Results Thirty‐seven patients completed ≥ one cycle of SM‐88 Regimen (response evaluable population). Disease control rate (DCR), overall survival (OS), and progression‐free survival (PFS) did not differ significantly between dose levels. Stable disease was achieved in 9/37 patients (DCR, 24.3%); there were no complete or partial responses. Quality‐of‐life (QOL) was maintained and trended in favor of 920 mg. SM‐88 Regimen was well tolerated; a single patient (1/49) had related grade 3 and 4 adverse events, which later resolved. In the intention‐to‐treat population of 49 patients, the median overall survival (mOS) was 3.4 months (95% CI: 2.7–4.9 months). Those treated in the second line had an mOS of 8.1 months and a median PFS of 3.8 months. Survival was higher for patients with stable versus progressive disease (any line; mOS: 10.6 months vs. 3.9 months; p = 0.01). Conclusions SM‐88 Regimen has a favorable safety profile with encouraging QOL effects, disease control, and survival trends. This regimen should be explored in the second‐line treatment of patients with mPDAC. ClinicalTrials.gov Identifier: NCT03512756.https://doi.org/10.1002/cam4.4768 |
| spellingShingle | Marcus S. Noel Semmie Kim Marion L. Hartley Steve Wong Vincent J. Picozzi Harry Staszewski Dae Won Kim Jan M. Van Tornout Philip Agop Philip Vincent Chung Allyson J. Ocean Andrea Wang‐Gillam A randomized phase II study of SM‐88 plus methoxsalen, phenytoin, and sirolimus in patients with metastatic pancreatic cancer treated in the second line and beyond Cancer Medicine |
| title | A randomized phase II study of SM‐88 plus methoxsalen, phenytoin, and sirolimus in patients with metastatic pancreatic cancer treated in the second line and beyond |
| title_full | A randomized phase II study of SM‐88 plus methoxsalen, phenytoin, and sirolimus in patients with metastatic pancreatic cancer treated in the second line and beyond |
| title_fullStr | A randomized phase II study of SM‐88 plus methoxsalen, phenytoin, and sirolimus in patients with metastatic pancreatic cancer treated in the second line and beyond |
| title_full_unstemmed | A randomized phase II study of SM‐88 plus methoxsalen, phenytoin, and sirolimus in patients with metastatic pancreatic cancer treated in the second line and beyond |
| title_short | A randomized phase II study of SM‐88 plus methoxsalen, phenytoin, and sirolimus in patients with metastatic pancreatic cancer treated in the second line and beyond |
| title_sort | randomized phase ii study of sm 88 plus methoxsalen phenytoin and sirolimus in patients with metastatic pancreatic cancer treated in the second line and beyond |
| url | https://doi.org/10.1002/cam4.4768 |
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