Vermandel M, Dupont C, Lecomte F, Quidet M, Le Rhun E, Mordon S, Reyns N
An introduction to indygo: set-up and preliminary results of the first pilot clinical trial on intraoperative 5-ala pdt for the treatment of newly diagnosed glioblastoma
ASLMS 2017, San Diego, CA
An introduction to indygo: set-up and preliminary results of the first pilot clinical trial on intraoperative 5-ala pdt for the treatment of newly diagnosed glioblastoma
ASLMS 2017, San Diego, CA
Abstract:
Glioblastoma (GBM) is a rare neoplastic disease and still remains an incurable brain tumor with a median overall survival of approximately 16 months. Despite of its low prevalence (0.3/10,000 persons), it is the most frequent primary malignant brain tumor in adults and no existing therapeutic agent is able to stop GBM progression. Complete tumor resection is rarely feasible, since tumor cells usually infiltrate brain surrounding tumor core. Adjuvant therapies to improve local control are thus highly expected. Management of newly diagnosed GBM includes surgery for maximal tumor resection followed by radiation therapy and concomitant and adjuvant chemotherapy. Recently, 5-ALA interstitial photodynamic therapies have been reported with promising results. However, if one consider the absence of controlled clinical trial, efficacy of 5-ALA PDT is not still evidenced and thus not included in the standard protocol. We present here the set-up of clinical trial to evaluate 5-ALA PDT to treat newly diagnosed GBM.
Our group has recently developed a specific light applicator to deliver PDT in the surgical cavity early after maximal resection to demonstrate 5-ALA-PDT efficacy on newly diagnosed GBM. Treatment of the infiltrating cells by a PDT effect is expected in the first millimeters of the cavity borders. Intraoperative PDT is a seamless strategy easily embeddable into the standard surgical protocol, which is more ethically acceptable and more efficient to assess PDT efficacy.
Ten patients will be enrolled and will undergo to intraoperative PDT in addition to the standard of care. PDT will be delivered early after maximal resection with 25 J/cm2 delivered at 5 mm of the surgical cavity borders. Total light dose will be delivered with 5 fractions of 5 J/cm2 each (off-period of 2 minutes between each fraction). A first early post-operative MRI will be acquired and, then, MRI will be acquired quarterly for monitoring.
Primary endpoint is the feasibility of intraoperative PDT, estimated by the proportion of patients who undergone intraoperative PDT without unacceptable toxicity. The objective is 70% that is 7 of 10 patients without unacceptable toxicity in relation to PDT. Secondary endpoints are progression-free survival, overall survival, and evaluation at 3 months, 6 months and 12 months of radiation treatment response and patients' quality of life.
Finally, after the feasibility and the absence of adverse effects, multicentric, parallel-group, randomized controlled trial (RCT) will be set-up to evaluate the efficacy of 5-ALA PDT for the treatment of newly diagnosed GBM. This multicenter clinical trial will be set-up and performed with the support of the European network Synaps (http://www.synaps-project.eu).
Glioblastoma (GBM) is a rare neoplastic disease and still remains an incurable brain tumor with a median overall survival of approximately 16 months. Despite of its low prevalence (0.3/10,000 persons), it is the most frequent primary malignant brain tumor in adults and no existing therapeutic agent is able to stop GBM progression. Complete tumor resection is rarely feasible, since tumor cells usually infiltrate brain surrounding tumor core. Adjuvant therapies to improve local control are thus highly expected. Management of newly diagnosed GBM includes surgery for maximal tumor resection followed by radiation therapy and concomitant and adjuvant chemotherapy. Recently, 5-ALA interstitial photodynamic therapies have been reported with promising results. However, if one consider the absence of controlled clinical trial, efficacy of 5-ALA PDT is not still evidenced and thus not included in the standard protocol. We present here the set-up of clinical trial to evaluate 5-ALA PDT to treat newly diagnosed GBM.
Our group has recently developed a specific light applicator to deliver PDT in the surgical cavity early after maximal resection to demonstrate 5-ALA-PDT efficacy on newly diagnosed GBM. Treatment of the infiltrating cells by a PDT effect is expected in the first millimeters of the cavity borders. Intraoperative PDT is a seamless strategy easily embeddable into the standard surgical protocol, which is more ethically acceptable and more efficient to assess PDT efficacy.
Ten patients will be enrolled and will undergo to intraoperative PDT in addition to the standard of care. PDT will be delivered early after maximal resection with 25 J/cm2 delivered at 5 mm of the surgical cavity borders. Total light dose will be delivered with 5 fractions of 5 J/cm2 each (off-period of 2 minutes between each fraction). A first early post-operative MRI will be acquired and, then, MRI will be acquired quarterly for monitoring.
Primary endpoint is the feasibility of intraoperative PDT, estimated by the proportion of patients who undergone intraoperative PDT without unacceptable toxicity. The objective is 70% that is 7 of 10 patients without unacceptable toxicity in relation to PDT. Secondary endpoints are progression-free survival, overall survival, and evaluation at 3 months, 6 months and 12 months of radiation treatment response and patients' quality of life.
Finally, after the feasibility and the absence of adverse effects, multicentric, parallel-group, randomized controlled trial (RCT) will be set-up to evaluate the efficacy of 5-ALA PDT for the treatment of newly diagnosed GBM. This multicenter clinical trial will be set-up and performed with the support of the European network Synaps (http://www.synaps-project.eu).
