Richard Riedel

Overview:

Novel therapies for soft tissue and bone sarcomas

Positions:

Associate Professor of Medicine

Medicine, Medical Oncology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 2000

Thomas Jefferson University

Resident in Medicine, Medicine

Duke University

Fellow in Hematology-Oncology, Medicine

Duke University

Fellow in Hematology-Oncology, Medicine

Duke University

Grants:

An International, Multicenter, Open-label, Randomized, Phase 3 Study of BLU-285 vs Regorafenib in Patients with Locally Advanced Unresectable or Metastatic Gastrointestinal Stromal Tumor (GIST)

Administered By
Duke Cancer Institute
Awarded By
Blueprint Medicines Corporation
Role
Principal Investigator
Start Date
End Date

Dissecting Mechanisms of Metastasis Through Comparative Systems Genetics

Administered By
Radiation Oncology
Awarded By
National Institutes of Health
Role
Investigator
Start Date
End Date

A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial of Nirogacestat Versus Placebo in Adult Patients With Progressing Desmoid Tumors/Aggressive Fibromatosis (DT/AF)

Administered By
Duke Cancer Institute
Awarded By
SpringWorks Therapeutics
Role
Principal Investigator
Start Date
End Date

A Phase 3, Interventional, Randomized, Multicenter, Open-Label Study of DCC-2618 vs Sunitinib in Patients with Advanced Gastrointestinal Stromal Tumors after Treatment with Imatinib

Administered By
Duke Cancer Institute
Awarded By
Deciphera Pharmaceuticals, LLC
Role
Principal Investigator
Start Date
End Date

A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Determine the Efficacy and Safety of MB305 in Unresectable Locally-advanced or Metastatic NY-ESO-1+ Synovial Sarcoma Subjects Following First-line Systemic Anti-cancer Therapy

Administered By
Duke Cancer Institute
Awarded By
Immune Design Corp.
Role
Principal Investigator
Start Date
End Date

Publications:

Dual-Energy CT Vital Iodine Tumor Burden for Response Assessment in Patients With Metastatic GIST Undergoing TKI Therapy: Comparison to Standard CT and FDG PET/CT Criteria.

Background: CT-based criteria for assessing gastroinstestinal stromal tumor (GIST) response to tyroskine kinase inhibitor (TKI) therapy are limited partly because tumor attenuation is influenced by treatment-related changes including hemorrhage and calcification. Iodine concentration may be less impacted by such changes. Objective: To determine whether DECT vital iodine tumor burden (TB) provides improved differentiation between responders and non-responders in patients with metastatic GIST undergoing TKI therapy compared to established CT and PET/CT criteria. Methods: An anthropomorphic phantom with spherical inserts mimicking GIST lesions of varying iodine concentrations and having non-enhancing central necrotic cores underwent DECT to determine a threshold iodine concentration. Forty patients (median age 57 years; 25 women, 15 men) treated with TKI for metaststic GIST were retrospectively evaluated. Patients underwent baseline and follow-up DECT and FDG PET/CT. Response assessment was performed using RECIST 1.1, modified Choi (mChoi), vascular tumor burden (VTB), DECT vital iodine TB, and European Organization for Research and Treatment of Cancer (EORTC PET) criteria. DECT vital iodine TB used the same percentage changes as RECIST 1.1 response categories. Progression-free survival (PFS) was compared between responders and non-responders for each response criteria using Cox proportional hazard ratios and Harrell's c-indices. Results: The phantom experiment identified a 0.5 mg/mL threshold to differentiate vital from non-vital tissue. Using DECT vital iodine TB, median PFS was significantly different between non-responders and responders (587 vs 167 days, respectively; p=.02). Hazard ratio for progression for DECT vital iodine TB non-responders versus responders was 6.9, versus 7.6 for EORTC PET, 3.3 for VTB, 2.3 for RECIST 1.1, and 2.1 for mChoi. C-index was 0.74 for EORTC PET, 0.73 for DECT vital iodine TB, 0.67 for VTB, 0.61 for RECIST 1.1, and 0.58 for mChoi. C-index was significantly greater for DECT vital iodine TB than RECIST 1.1 (p=.02) and mChoi (p=.002), but not different than VTB and EORTC PET (p>.05). Conclusion: DECT vital iodine TB criteria showed comparable performance as EORTC PET and outperformed RECIST 1.1 and mChoi for response assessment of metastatic GIST under TKI therapy. Clinical Impact: DECT vital iodine TB could help guide early management decisions in patients on TKI therapy.
Authors
Meyer, M; Hohenberger, P; Overhoff, D; Bartsch, A; Henzler, T; Haubenreisser, H; Ronald, J; Schmidt, B; Flohr, T; Sedlmair, M; Ota, H; Messiou, C; Schoenberg, SO; Riedel, RF; Nelson, RC; Marin, D
URI
https://scholars.duke.edu/individual/pub1499246
PMID
34668385
Source
pubmed
Published In
Ajr. American Journal of Roentgenology
Published Date
DOI
10.2214/AJR.21.26636

nab-Sirolimus for Patients With Malignant Perivascular Epithelioid Cell Tumors.

PURPOSE: Malignant perivascular epithelioid cell tumor (PEComa) is a rare aggressive sarcoma, with no approved treatment. To our knowledge, this phase II, single-arm, registration trial is the first prospective clinical trial in this disease, investigating the safety and efficacy of the mammalian target of rapamycin inhibitor nab-sirolimus (AMPECT, NCT02494570). PATIENTS AND METHODS: Patients with malignant PEComa were treated with nab-sirolimus 100 mg/m2 intravenously once weekly for 2 weeks in 3-week cycles. The primary end point was objective response rate evaluated by independent radiology review. Key secondary end points included duration of response, progression-free survival, and safety. A key exploratory end point was tumor biomarker analysis. RESULTS: Thirty-four patients were treated (safety evaluable), and 31 were evaluable for efficacy. The overall response rate was 39% (12 of 31; 95% CI, 22 to 58) with one complete and 11 partial responses, 52% (16 of 31) of patients had stable disease, and 10% (3 of 31) had progressive disease. Responses were of rapid onset (67% by week 6) and durable. Median duration of response was not reached after a median follow-up for response of 2.5 years, with 7 of 12 responders with treatment ongoing (range 5.6-47.2+ months). Twenty-five of 31 patients had tumor mutation profiling: 8 of 9 (89%) patients with a TSC2 mutation achieved a confirmed response versus 2 of 16 (13%) without TSC2 mutation (P < .001). The median progression-free survival was 10.6 months (95% CI, 5.5 months to not reached), and the median overall survival was 40.8 months (95% CI, 22.2 months to not reached). Most treatment-related adverse events were grade 1 or 2 and were manageable for long-term treatment. No grade ≥ 4 treatment-related events occurred. CONCLUSION: nab-Sirolimus is active in patients with malignant PEComa. The response rate, durability of response, disease control rate, and safety profile support that nab-sirolimus represents an important new treatment option for this disease.
Authors
Wagner, AJ; Ravi, V; Riedel, RF; Ganjoo, K; Van Tine, BA; Chugh, R; Cranmer, L; Gordon, EM; Hornick, JL; Du, H; Grigorian, B; Schmid, AN; Hou, S; Harris, K; Kwiatkowski, DJ; Desai, NP; Dickson, MA
MLA Citation
Wagner, Andrew J., et al. “nab-Sirolimus for Patients With Malignant Perivascular Epithelioid Cell Tumors.J Clin Oncol, Oct. 2021, p. JCO2101728. Pubmed, doi:10.1200/JCO.21.01728.
URI
https://scholars.duke.edu/individual/pub1499333
PMID
34637337
Source
pubmed
Published In
Journal of Clinical Oncology
Published Date
Start Page
JCO2101728
DOI
10.1200/JCO.21.01728

Identified Enrollment Challenges of Adolescent and Young Adult Patients on the Nonchemotherapy Arm of Children's Oncology Group Study ARST1321.

ARST1321, a trial of patients with advanced soft tissue sarcoma, was the first National Clinical Trials Network study codeveloped by pediatric and adult consortia with two treatment cohorts. We report on the findings of a survey to identify barriers to enrolling adolescent and young adult patients (15-39 years) onto the nonchemotherapy arm. The survey response rate was 31% with a 70% completion rate. Common identified reasons for low accrual in order of decreasing frequency included insufficient funding, lack of study awareness or interest, competing trials, toxicity concerns, philosophical differences in the therapy backbone, and regulatory and infrastructure barriers. Clinical Trials.gov ID: NCT02180867.
Authors
Avutu, V; Weiss, AR; Reed, DR; Ahmed, SK; Allen-Rhoades, WA; Chen, Y-LE; Davis, LE; Eaton, BR; Hawkins, DS; Indelicato, DJ; Patel, SR; Randall, RL; Reinke, DK; Riedel, RF; Scharschmidt, TJ; Thornton, KA; Wang, D; Janeway, KA; Kopp, LM
MLA Citation
Avutu, Viswatej, et al. “Identified Enrollment Challenges of Adolescent and Young Adult Patients on the Nonchemotherapy Arm of Children's Oncology Group Study ARST1321.J Adolesc Young Adult Oncol, Sept. 2021. Pubmed, doi:10.1089/jayao.2021.0103.
URI
https://scholars.duke.edu/individual/pub1497171
PMID
34515544
Source
pubmed
Published In
J Adolesc Young Adult Oncol
Published Date
DOI
10.1089/jayao.2021.0103

Phase II Randomized Study of CMB305 and Atezolizumab Compared With Atezolizumab Alone in Soft-Tissue Sarcomas Expressing NY-ESO-1.

PURPOSE: CMB305 is a heterologous prime-boost vaccination regimen created to prime NY-ESO-1-specific CD8 T-cell populations and then activate the immune response with a potent TLR-4 agonist. This open-label randomized phase II trial was designed to investigate the efficacy and safety of adding the CMB305 regimen to atezolizumab (anti-programmed death ligand-1 therapy) in comparison with atezolizumab alone in patients with synovial sarcoma or myxoid liposarcoma. PATIENTS AND METHODS: Patients with locally advanced, relapsed, or metastatic synovial sarcoma or myxoid liposarcoma (any grade) were randomly assigned to receive CMB305 with atezolizumab (experimental arm) or atezolizumab alone (control arm). The primary end points were progression-free survival (PFS) and overall survival (OS) analyzed using the Kaplan-Meier method. Safety and immune responses were assessed. RESULTS: A total of 89 patients were enrolled; 55.1% had received ≥ 2 prior lines of chemotherapy. Median PFS was 2.6 months and 1.6 months in the combination and control arms, respectively (hazard ratio, 0.9; 95% CI, 0.6 to 1.3). Median OS was 18 months in both treatment arms. Patients treated with combination therapy had a significantly higher rate of treatment-induced NY-ESO-1-specific T cells (P = .01) and NY-ESO-1-specific antibody responses (P < .0001). In a post hoc analysis of all dosed patients, OS was longer (36 months) in the subset who developed anti-NY-ESO-1 T-cell immune response (hazard ratio, 0.3; P = .02). CONCLUSION: Although the combination of CMB305 and atezolizumab did not result in significant increases in PFS or OS compared with atezolizumab alone, some patients demonstrated evidence of an anti-NY-ESO-1 immune response and appeared to fare better by imaging than those without such an immune response. Combining prime-boost vaccines such as CMB305 with anti-programmed death ligand-1 therapies merits further evaluation in other clinical contexts.
Authors
Chawla, SP; Van Tine, BA; Pollack, SM; Ganjoo, KN; Elias, AD; Riedel, RF; Attia, S; Choy, E; Okuno, SH; Agulnik, M; von Mehren, M; Livingston, MB; Keedy, VL; Verschraegen, CF; Philip, T; Bohac, GC; Yurasov, S; Yakovich, A; Lu, H; Chen, M; Maki, RG
MLA Citation
Chawla, Sant P., et al. “Phase II Randomized Study of CMB305 and Atezolizumab Compared With Atezolizumab Alone in Soft-Tissue Sarcomas Expressing NY-ESO-1.J Clin Oncol, July 2021, p. JCO2003452. Pubmed, doi:10.1200/JCO.20.03452.
URI
https://scholars.duke.edu/individual/pub1489114
PMID
34260265
Source
pubmed
Published In
Journal of Clinical Oncology
Published Date
Start Page
JCO2003452
DOI
10.1200/JCO.20.03452

Health-related quality of life and pain with selinexor in patients with advanced dedifferentiated liposarcoma.

Objective: Compare health-related quality of life (HRQoL) of selinexor versus placebo in patients with dedifferentiated liposarcoma. Materials & methods: HRQoL was assessed at baseline and day 1 of each cycle using the European Organization for Research and Treatment of Cancer 30-item core quality of life questionnaire. Results were reported from baseline to day 169 (where exposure to treatment was maximized while maintaining adequate sample size). Results: Pain scores worsened for placebo versus selinexor across all postbaseline visits, although differences in HRQoL at some visits were not significant. Other domains did not exhibit significant differences between arms; however, scores in both arms deteriorated over time. Conclusion: Patients treated with selinexor reported lower rates and slower worsening of pain compared with patients who received placebo.
Authors
Gounder, M; Abdul Razak, AR; Gilligan, AM; Leong, H; Ma, X; Somaiah, N; Chawla, SP; Martin-Broto, J; Grignani, G; Schuetze, SM; Vincenzi, B; Wagner, AJ; Chmielowski, B; Jones, RL; Shah, J; Shacham, S; Kauffman, M; Riedel, RF; Attia, S
MLA Citation
Gounder, Mrinal, et al. “Health-related quality of life and pain with selinexor in patients with advanced dedifferentiated liposarcoma.Future Oncol, vol. 17, no. 22, Aug. 2021, pp. 2923–39. Pubmed, doi:10.2217/fon-2021-0284.
URI
https://scholars.duke.edu/individual/pub1480790
PMID
33855868
Source
pubmed
Published In
Future Oncol
Volume
17
Published Date
Start Page
2923
End Page
2939
DOI
10.2217/fon-2021-0284