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Papers by Priya Kumthekar

Frontiers in Oncology, Sep 27, 2018

Journal of Clinical Oncology, May 20, 2014

2072 Background: Current standard treatment for GBM is radiation (RT) and temozolomide (TMZ). We ... more 2072 Background: Current standard treatment for GBM is radiation (RT) and temozolomide (TMZ). We published phase I data of the addition of arsenic trioxide (ATO) to RT and TMZ. We now present the phase II data. Methods: Patients with newly diagnosed malignant gliomas were eligible for treatment in this single arm phase II. Patients were treated with RT (60GY), TMZ (75 mg/m2 daily x 42 days) and ATO 0.20 mg/kg daily in week 1 then twice a week x 5 weeks. Results: Twenty-five patients (14 M and 11 W) were enrolled with a median age of 56 (28-73). Histology was GBM 18, AA 6 and AO 1. All patients completed RT/TMZ/ATO. Median number of post RT cycles of TMZ was 3 (0-12); 9 patients completed 6 or more cycles. Median PFS was 6 m for GBM and 15 m for AG and median OS was 15 m for GBM and NR for AA. Response was SD in 20, PR in 1 and PD in 4. Conclusions: Adding ATO to RT and TMZ is feasible and tolerable but does not appear to improve outcome compared to RTOG 0525 data where OS is 16.6 months in newly diagnosed...

Neuro-oncology, Nov 1, 2016

Neuro-oncology, Nov 1, 2018

Acta Neuropathologica, Sep 23, 2016

Neuro-oncology, Nov 1, 2019

Scientific Reports, Nov 28, 2019

Neuro-oncology, Nov 1, 2016

Nature Medicine, May 15, 2023

Molecular Cancer Research, 2018

Research Square (Research Square), Feb 3, 2023

Neuro-oncology, Nov 1, 2016

Neuro-oncology, Sep 1, 2014

Neuro-oncology, Nov 1, 2017

Neuro-oncology, Nov 1, 2014

Lancet Oncology, Aug 1, 2021

BACKGROUND Malignant glioma is the most common and lethal primary brain tumour, with dismal survi... more BACKGROUND Malignant glioma is the most common and lethal primary brain tumour, with dismal survival rates and no effective treatment. We examined the safety and activity of NSC-CRAd-S-pk7, an engineered oncolytic adenovirus delivered by neural stem cells (NSCs), in patients with newly diagnosed high-grade glioma. METHODS This was a first-in-human, open-label, phase 1, dose-escalation trial done to determine the maximal tolerated dose of NSC-CRAd-S-pk7, following a 3 + 3 design. Patients with newly diagnosed, histologically confirmed, high-grade gliomas (WHO grade III or IV) were recruited. After neurosurgical resection, NSC-CRAd-S-pk7 was injected into the walls of the resection cavity. The first patient cohort received a dose starting at 6·25 × 1010 viral particles administered by 5·00 × 107 NSCs, the second cohort a dose of 1·25 × 1011 viral particles administered by 1·00 × 108 NSCs, and the third cohort a dose of 1·875 × 1011 viral particles administered by 1·50 × 108 NSCs. No further dose escalation was planned. Within 10-14 days, treatment with temozolomide and radiotherapy was initiated. Primary endpoints were safety and toxicity profile and the maximum tolerated dose for a future phase 2 trial. All analyses were done in all patients who were included in the trial and received the study treatment and were not excluded from the study. Recruitment is complete and the trial is finished. The trial is registered with ClinicalTrials.gov, NCT03072134. FINDINGS Between April 24, 2017, and Nov 13, 2019, 12 patients with newly diagnosed, malignant gliomas were recruited and included in the safety analysis. Histopathological evaluation identified 11 (92%) of 12 patients with glioblastoma and one (8%) of 12 patients with anaplastic astrocytoma. The median follow-up was 18 months (IQR 14-22). One patient receiving 1·50 × 108 NSCs loading 1·875 × 1011 viral particles developed viral meningitis (grade 3) due to the inadvertent injection of NSC-CRAd-S-pk7 into the lateral ventricle. Otherwise, treatment was safe as no formal dose-limiting toxicity was reached, so 1·50 × 108 NSCs loading 1·875 × 1011 viral particles was recommended as a phase 2 trial dose. There were no treatment-related deaths. The median progression-free survival was 9·1 months (95% CI 8·5-not reached) and median overall survival was 18·4 months (15·7-not reached). INTERPRETATION NSC-CRAd-S-pk7 treatment was feasible and safe. Our immunological and histopathological findings support continued investigation of NSC-CRAd-S-pk7 in a phase 2/3 clinical trial. FUNDING US National Institutes of Health.

Frontiers in Oncology, Sep 27, 2018

Journal of Clinical Oncology, May 20, 2014

2072 Background: Current standard treatment for GBM is radiation (RT) and temozolomide (TMZ). We ... more 2072 Background: Current standard treatment for GBM is radiation (RT) and temozolomide (TMZ). We published phase I data of the addition of arsenic trioxide (ATO) to RT and TMZ. We now present the phase II data. Methods: Patients with newly diagnosed malignant gliomas were eligible for treatment in this single arm phase II. Patients were treated with RT (60GY), TMZ (75 mg/m2 daily x 42 days) and ATO 0.20 mg/kg daily in week 1 then twice a week x 5 weeks. Results: Twenty-five patients (14 M and 11 W) were enrolled with a median age of 56 (28-73). Histology was GBM 18, AA 6 and AO 1. All patients completed RT/TMZ/ATO. Median number of post RT cycles of TMZ was 3 (0-12); 9 patients completed 6 or more cycles. Median PFS was 6 m for GBM and 15 m for AG and median OS was 15 m for GBM and NR for AA. Response was SD in 20, PR in 1 and PD in 4. Conclusions: Adding ATO to RT and TMZ is feasible and tolerable but does not appear to improve outcome compared to RTOG 0525 data where OS is 16.6 months in newly diagnosed...

Neuro-oncology, Nov 1, 2016

Neuro-oncology, Nov 1, 2018

Acta Neuropathologica, Sep 23, 2016

Neuro-oncology, Nov 1, 2019

Scientific Reports, Nov 28, 2019

Neuro-oncology, Nov 1, 2016

Nature Medicine, May 15, 2023

Molecular Cancer Research, 2018

Research Square (Research Square), Feb 3, 2023

Neuro-oncology, Nov 1, 2016

Neuro-oncology, Sep 1, 2014

Neuro-oncology, Nov 1, 2017

Neuro-oncology, Nov 1, 2014

Lancet Oncology, Aug 1, 2021

BACKGROUND Malignant glioma is the most common and lethal primary brain tumour, with dismal survi... more BACKGROUND Malignant glioma is the most common and lethal primary brain tumour, with dismal survival rates and no effective treatment. We examined the safety and activity of NSC-CRAd-S-pk7, an engineered oncolytic adenovirus delivered by neural stem cells (NSCs), in patients with newly diagnosed high-grade glioma. METHODS This was a first-in-human, open-label, phase 1, dose-escalation trial done to determine the maximal tolerated dose of NSC-CRAd-S-pk7, following a 3 + 3 design. Patients with newly diagnosed, histologically confirmed, high-grade gliomas (WHO grade III or IV) were recruited. After neurosurgical resection, NSC-CRAd-S-pk7 was injected into the walls of the resection cavity. The first patient cohort received a dose starting at 6·25 × 1010 viral particles administered by 5·00 × 107 NSCs, the second cohort a dose of 1·25 × 1011 viral particles administered by 1·00 × 108 NSCs, and the third cohort a dose of 1·875 × 1011 viral particles administered by 1·50 × 108 NSCs. No further dose escalation was planned. Within 10-14 days, treatment with temozolomide and radiotherapy was initiated. Primary endpoints were safety and toxicity profile and the maximum tolerated dose for a future phase 2 trial. All analyses were done in all patients who were included in the trial and received the study treatment and were not excluded from the study. Recruitment is complete and the trial is finished. The trial is registered with ClinicalTrials.gov, NCT03072134. FINDINGS Between April 24, 2017, and Nov 13, 2019, 12 patients with newly diagnosed, malignant gliomas were recruited and included in the safety analysis. Histopathological evaluation identified 11 (92%) of 12 patients with glioblastoma and one (8%) of 12 patients with anaplastic astrocytoma. The median follow-up was 18 months (IQR 14-22). One patient receiving 1·50 × 108 NSCs loading 1·875 × 1011 viral particles developed viral meningitis (grade 3) due to the inadvertent injection of NSC-CRAd-S-pk7 into the lateral ventricle. Otherwise, treatment was safe as no formal dose-limiting toxicity was reached, so 1·50 × 108 NSCs loading 1·875 × 1011 viral particles was recommended as a phase 2 trial dose. There were no treatment-related deaths. The median progression-free survival was 9·1 months (95% CI 8·5-not reached) and median overall survival was 18·4 months (15·7-not reached). INTERPRETATION NSC-CRAd-S-pk7 treatment was feasible and safe. Our immunological and histopathological findings support continued investigation of NSC-CRAd-S-pk7 in a phase 2/3 clinical trial. FUNDING US National Institutes of Health.