Annick Desjardins

Positions:

Associate Professor of Neurosurgery

Neurosurgery, Neuro-Oncology
School of Medicine

Associate Professor in Neurology

Neurology, General & Community Neurology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 1998

University of Sherbrooke

Resident, Neurology

University of Sherbrooke

Fellow in Neuro-Oncology, Medicine

Duke University

Grants:

Phase 3 randomized, open-label study to evaluate Eflornithine with Lomustine compared to Lomustine (STELLAR) alone in patients with Anaplastic Astrocytoma

Administered By
Duke Cancer Institute
Role
Principal Investigator
Start Date
End Date

Ph1 Study of Marizomib and Bevacizumab-Naive Subjects with Grade IV Malignant Glioma

Administered By
Duke Cancer Institute
Role
Principal Investigator
Start Date
End Date

Phase 1b, Multicenter, Open-Label Study of Marizomib with Temozolomide and Radiotherapy in Patients with Newly Diagnosed WHO Grade IV Malignant Glioma

Administered By
Duke Cancer Institute
Role
Principal Investigator
Start Date
End Date

A Phase 1 Dose Escalation Study Evaluating the Safety and Tolerability of PF-06840003 in Patients with Malignant Glioma

Administered By
Duke Cancer Institute
Role
Principal Investigator
Start Date
End Date

Phase 2 study of SYM004 for adult patients with recurrent glioblastoma

Administered By
Duke Cancer Institute
Role
Principal Investigator
Start Date
End Date

Publications:

Phase 1b/2a study of galunisertib, a small molecule inhibitor of transforming growth factor-beta receptor I, in combination with standard temozolomide-based radiochemotherapy in patients with newly diagnosed malignant glioma.

Purpose Galunisertib, a TGF-β inhibitor, has demonstrated antitumor effects in preclinical and radiographic responses in some patients with malignant glioma. This Phase 1b/2a trial investigated the clinical benefit of combining galunisertib with temozolomide-based radiochemotherapy (TMZ/RTX) in patients with newly diagnosed malignant glioma (NCT01220271). Methods This is an open-label, 2-arm Phase 1b/2a study (N = 56) of galunisertib (intermittent dosing: 14 days on/14 days off per cycle of 28 days) in combination with TMZ/RTX (n = 40), versus a control arm (TMZ/RTX, n = 16). The primary objective of Phase 1b was to determine the safe and tolerable Phase 2 dose of galunisertib. The primary objective of Phase 2a was to confirm the tolerability and pharmacodynamic profile of galunisertib with TMZ/RTX, and the secondary objectives included determining the efficacy and pharmacokinetic (PK) profile of galunisertib with TMZ/RTX in patients with glioblastoma. This study also characterized the changes in the major T-cell subsets during TMZ/RTX plus galunisertib treatment. Results In the Phase 2a study, efficacy results for patients treated with galunisertib plus TMZ/RTX or TMZ/RTX were: median overall survival (18.2 vs 17.9 months), median progression-free survival (7.6 vs 11.5 months), and disease control rate (80% [32/40] vs 56% [9/16] patients) respectively. PK profile of galunisertib plus TMZ/RTX regimen was consistent with previously published PK data of galunisertib. The overall safety profile across treatment arms was comparable. Conclusion No differences in efficacy, safety or pharmacokinetic variables were observed between the two treatment arms.
Authors
Wick, A; Desjardins, A; Suarez, C; Forsyth, P; Gueorguieva, I; Burkholder, T; Cleverly, AL; Estrem, ST; Wang, S; Lahn, MM; Guba, SC; Capper, D; Rodon, J
URI
https://scholars.duke.edu/individual/pub1434005
PMID
32140889
Source
pubmed
Published In
Invest New Drugs
Published Date
DOI
10.1007/s10637-020-00910-9

Rindopepimut with Bevacizumab for Patients with Relapsed EGFRvIII-Expressing Glioblastoma (ReACT): Results of a Double-Blind Randomized Phase II Trial.

PURPOSE: Rindopepimut is a vaccine targeting the tumor-specific EGF driver mutation, EGFRvIII. The ReACT study investigated whether the addition of rindopepimut to standard bevacizumab improved outcome for patients with relapsed, EGFRvIII-positive glioblastoma. PATIENTS AND METHODS: In this double-blind, randomized, phase II study (NCT01498328) conducted at 26 hospitals in the United States, bevacizumab-naïve patients with recurrent EGFRvIII-positive glioblastoma were randomized to receive rindopepimut or a control injection of keyhole limpet hemocyanin, each concurrent with bevacizumab. The primary endpoint was 6-month progression-free survival (PFS6) by central review with a one-sided significance of 0.2. RESULTS: Between May 2012 and 2014, 73 patients were randomized (36 rindopepimut, 37 control). Rindopepimut toxicity included transient, low-grade local reactions. As primary endpoint, PFS6 was 28% (10/36) for rindopepimut compared with 16% (6/37) for control (P = 0.12, one-sided). Secondary and exploratory endpoints also favored the rindopepimut group including a statistically significant survival advantage [HR, 0.53; 95% confidence interval (CI), 0.32-0.88; two-sided log-rank P = 0.01], a higher ORR [30% (9/30) vs. 18% (6/34; P = 0.38)], median duration of response [7.8 months (95% CI, 3.5-22.2) vs. 5.6 (95% CI, 3.7-7.4)], and ability to discontinue steroids for ≥6 months [33% (6/18) vs. 0% (0/19)]. Eighty percent of rindopepimut-treated patients achieved robust anti-EGFRvIII titers (≥1:12,800), which were associated with prolonged survival (HR = 0.17; 95% CI, 0.07-0.45; P < 0.0001). CONCLUSIONS: Our randomized trial supports the potential for targeted immunotherapy among patients with GBM, but the therapeutic benefit requires validation due to the small sample size and potential heterogeneity of bevacizumab response among recurrent patients with GBM.See related commentary by Wick and Wagener, p. 1535.
Authors
Reardon, DA; Desjardins, A; Vredenburgh, JJ; O'Rourke, DM; Tran, DD; Fink, KL; Nabors, LB; Li, G; Bota, DA; Lukas, RV; Ashby, LS; Duic, JP; Mrugala, MM; Cruickshank, S; Vitale, L; He, Y; Green, JA; Yellin, MJ; Turner, CD; Keler, T; Davis, TA; Sampson, JH; ReACT trial investigators,
MLA Citation
Reardon, David A., et al. “Rindopepimut with Bevacizumab for Patients with Relapsed EGFRvIII-Expressing Glioblastoma (ReACT): Results of a Double-Blind Randomized Phase II Trial.Clin Cancer Res, vol. 26, no. 7, Apr. 2020, pp. 1586–94. Pubmed, doi:10.1158/1078-0432.CCR-18-1140.
URI
https://scholars.duke.edu/individual/pub1431799
PMID
32034072
Source
pubmed
Published In
Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Volume
26
Published Date
Start Page
1586
End Page
1594
DOI
10.1158/1078-0432.CCR-18-1140

Second primary cancers in long-term survivors of glioblastoma.

Background: Overall survival (OS) in glioblastoma (GBM) is poor at an average of 14 to 18 months, and long-term survivors (LTS) of GBM are rare. LTS of GBM, defined as surviving >5 years postdiagnosis, represent only 2% to 10% of all GBM patients. LTS of cancer are at high risk of developing second primary neoplasms. This study looks at occurrences of second primary neoplasms in LTS of GBM. Methods: Records from adult patients newly diagnosed with GBM between January 1, 1998 and February 8, 2010, were retrospectively reviewed to identify LTS, defined as patients who survived ≥5 years. We focused on the identification of a new diagnosis of cancer occurring at least 2 years after the initial GBM diagnosis. Results: We identified 155 LTS of GBM, with a median OS of 11.0 years (95% CI: 9.0 to 13.1 years) and a median follow-up of 9.6 years (95% CI: 8.7 to 10.7 years). In this cohort of patients, 13 (8.4%) LTS of GBM developed 17 secondary cancers. Eight could potentially be attributed to previous radiation and chemotherapy (skin cancer in radiation field [n = 4], leukemia [n = 2], low-grade glioma [n = 1], and sarcoma of the scalp [n = 1]). The other 9 cases included melanoma (n = 2), prostate cancer (n = 2), bladder cancer (n = 1), endometrioid adenocarcinoma (n = 1), basal cell carcinoma (n = 1), and renal cell carcinoma (n = 1). Conclusions: Although second primary cancers are rare in GBM LTS, providers should continue close monitoring with appropriate oncologic care. Moreover, this highlights the need for survivorship care of patients with GBM.
Authors
Kim, J-Y; Jackman, JG; Woodring, S; McSherry, F; Herndon, JE; Desjardins, A; Friedman, HS; Peters, KB
MLA Citation
Kim, Jung-Young, et al. “Second primary cancers in long-term survivors of glioblastoma.Neurooncol Pract, vol. 6, no. 5, Sept. 2019, pp. 386–91. Pubmed, doi:10.1093/nop/npz001.
URI
https://scholars.duke.edu/individual/pub1411790
PMID
31555453
Source
pubmed
Published In
Neuro Oncology Practice
Volume
6
Published Date
Start Page
386
End Page
391
DOI
10.1093/nop/npz001

Randomized open-label phase II trial of 5-day aprepitant plus ondansetron compared to ondansetron alone in the prevention of chemotherapy-induced nausea-vomiting (CINV) in glioma patients receiving adjuvant temozolomide.

PURPOSE: CINV remains a distressing side effect experienced by glioma patients receiving multi-day temozolomide therapy, in spite of guideline-based antiemetic therapy with selective serotonin-receptor-antagonists. Antiemetic research with aprepitant has routinely excluded glioma patients. In this randomized open-label phase II study, use of a nonstandard 5-day regimen of aprepitant for glioma patients was investigated. METHODS: One hundred thirty-six glioma patients receiving their first cycle of adjuvant temozolomide (150-200 mg/m2/day × 5 days every 28 days) were randomized to Arm-A (ondansetron 8 mg days 1-5 with aprepitant day 1: 125 mg, days 2-5: 80 mg) or Arm-B (ondansetron). Randomization was stratified by tumor grade and number of prior chemotherapy regimens. The primary endpoint was the percentage of patients achieving complete control (CC), defined as no emetic episode or antiemetic rescue medication over the 7-day study period. Secondary endpoints included CINV efficacy in the acute phase (≤ 24 h) and delayed phase (days 2-7), as well as safety and quality of life (QoL). RESULTS: Patients were 61% male, 97% white, 48% with KPS > 90%, 60% non-smokers, mean age 54, 92% with low alcohol use, and 46% with a CINV history. The CC was 58.6% (Arm-A) and 54.5% (Arm-B). Acute-complete response (CR) rates, defined as CC on day 1 in Arm-A and -B, were 97.1% and 87.9%, respectively (p = 0.056). Treatment-related toxicities were mild or moderate in severity. CONCLUSIONS: Aprepitant plus ondansetron may increase acute-CR, may have benefit regarding CINV's effect on QoL, and is safe for 5-day temozolomide compared to ondansetron. This study provides no evidence that aprepitant increases CC rate over ondansetron alone.
Authors
Patel, MP; Woodring, S; Randazzo, DM; Friedman, HS; Desjardins, A; Healy, P; Herndon, JE; McSherry, F; Lipp, ES; Miller, E; Peters, KB; Affronti, ML
MLA Citation
URI
https://scholars.duke.edu/individual/pub1406357
PMID
31440823
Source
pubmed
Published In
Support Care Cancer
Volume
28
Published Date
Start Page
2229
End Page
2238
DOI
10.1007/s00520-019-05039-x

Rindopepimut with temozolomide for patients with newly diagnosed, EGFRvIII-expressing glioblastoma (ACT IV): a randomised, double-blind, international phase 3 trial.

BACKGROUND: Rindopepimut (also known as CDX-110), a vaccine targeting the EGFR deletion mutation EGFRvIII, consists of an EGFRvIII-specific peptide conjugated to keyhole limpet haemocyanin. In the ACT IV study, we aimed to assess whether or not the addition of rindopepimut to standard chemotherapy is able to improve survival in patients with EGFRvIII-positive glioblastoma. METHODS: In this randomised, double-blind, phase 3 trial, we recruited patients aged 18 years and older with glioblastoma from 165 hospitals in 22 countries. Eligible patients had newly diagnosed glioblastoma confirmed to express EGFRvIII by central analysis, and had undergone maximal surgical resection and completion of standard chemoradiation without progression. Patients were stratified by European Organisation for Research and Treatment of Cancer recursive partitioning analysis class, MGMT promoter methylation, and geographical region, and randomly assigned (1:1) with a prespecified randomisation sequence (block size of four) to receive rindopepimut (500 μg admixed with 150 μg GM-CSF) or control (100 μg keyhole limpet haemocyanin) via monthly intradermal injection until progression or intolerance, concurrent with standard oral temozolomide (150-200 mg/m2 for 5 of 28 days) for 6-12 cycles or longer. Patients, investigators, and the trial funder were masked to treatment allocation. The primary endpoint was overall survival in patients with minimal residual disease (MRD; enhancing tumour <2 cm2 post-chemoradiation by central review), analysed by modified intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01480479. FINDINGS: Between April 12, 2012, and Dec 15, 2014, 745 patients were enrolled (405 with MRD, 338 with significant residual disease [SRD], and two unevaluable) and randomly assigned to rindopepimut and temozolomide (n=371) or control and temozolomide (n=374). The study was terminated for futility after a preplanned interim analysis. At final analysis, there was no significant difference in overall survival for patients with MRD: median overall survival was 20·1 months (95% CI 18·5-22·1) in the rindopepimut group versus 20·0 months (18·1-21·9) in the control group (HR 1·01, 95% CI 0·79-1·30; p=0·93). The most common grade 3-4 adverse events for all 369 treated patients in the rindopepimut group versus 372 treated patients in the control group were: thrombocytopenia (32 [9%] vs 23 [6%]), fatigue (six [2%] vs 19 [5%]), brain oedema (eight [2%] vs 11 [3%]), seizure (nine [2%] vs eight [2%]), and headache (six [2%] vs ten [3%]). Serious adverse events included seizure (18 [5%] vs 22 [6%]) and brain oedema (seven [2%] vs 12 [3%]). 16 deaths in the study were caused by adverse events (nine [4%] in the rindopepimut group and seven [3%] in the control group), of which one-a pulmonary embolism in a 64-year-old male patient after 11 months of treatment-was assessed as potentially related to rindopepimut. INTERPRETATION: Rindopepimut did not increase survival in patients with newly diagnosed glioblastoma. Combination approaches potentially including rindopepimut might be required to show efficacy of immunotherapy in glioblastoma. FUNDING: Celldex Therapeutics, Inc.
Authors
Weller, M; Butowski, N; Tran, DD; Recht, LD; Lim, M; Hirte, H; Ashby, L; Mechtler, L; Goldlust, SA; Iwamoto, F; Drappatz, J; O'Rourke, DM; Wong, M; Hamilton, MG; Finocchiaro, G; Perry, J; Wick, W; Green, J; He, Y; Turner, CD; Yellin, MJ; Keler, T; Davis, TA; Stupp, R; Sampson, JH; ACT IV trial investigators,
MLA Citation
Weller, Michael, et al. “Rindopepimut with temozolomide for patients with newly diagnosed, EGFRvIII-expressing glioblastoma (ACT IV): a randomised, double-blind, international phase 3 trial.Lancet Oncol, vol. 18, no. 10, Oct. 2017, pp. 1373–85. Pubmed, doi:10.1016/S1470-2045(17)30517-X.
URI
https://scholars.duke.edu/individual/pub1274010
PMID
28844499
Source
pubmed
Published In
Lancet Oncol
Volume
18
Published Date
Start Page
1373
End Page
1385
DOI
10.1016/S1470-2045(17)30517-X