Introduction
Convection-enhanced delivery
Convective delivery properties
Bypasses the blood–brain barrier
Homogeneous distribution
Reliable
Safe
Targeted
Real-time imaging of perfusion
CED in clinical trials
Author | Year | Agent | Trial phase | WHO grade, tumor type (no. of pts) | No. of catheters | Catheter location (intratumoral vs. peritumoral) | Volume infused (ml) | Mean Vd | Duration | Median OS | Adverse Events |
---|---|---|---|---|---|---|---|---|---|---|---|
Laske et al | 1997 | TF-CRM107 | I | Recurrent Gr IV GBM (10), Gr III AA (5), AO (1), metastatic lung Ca (2) | 1–3 | Intratumoral | 5–180 | na | 2–16 days | 41 weeks (GBM patients only) | Cerebral edema, seizures |
Rand et al | 2000 | NBI-3001 (IL4-Pseudomonas exotoxin) | I | Recurrent Gr IV GBM (9) | 1–3 | Intratumoral | 30–185 | na | 4–8 days | ||
Weaver et al | 2003 | TF-CRM107 | II | Recurrent Gr IV GBM & Gr III AA (44) | 1–2 | Intratumoral | 40 | na | 4–5 days | 37 weeks | Cerebral edema, seizures |
Weber et al | 2003 | NBI-3001 (IL4-Pseudomonas exotoxin) | I | Recurrent Gr IV GBM (25) & Gr III AA (6) | 1–3 | Intratumoral | 40–100 | na | 4 days | 23.2 weeks (GBM patients only) | Seizures, headache, weakness, edema |
Voges et al | 2003 | HSV-tk | I/II | Recurrent Gr IV GBM (8) | 1–2 | Intratumoral | 30–60 | 3.0 (0.5–6.9) ml | 29 days | 28.1 weeks | Transient worsening of neurological condition, elevated body temperature |
Lidar et al | 2004 | Paclitaxel | I/II | Recurrent Gr IV GBM (13) & Gr III AA (2) | 1 | Intratumoral | 6 | na | 2–5 days | 16 weeks (GBM); 30 weeks including anaplastic astrocytoma | Chemical meningitis |
Patel et al | 2005 | Cotara* | I/II | Recurrent Gr IV GBM (37) & Gr III AA (6), newly diagnosed Gr IV GBM (8) | 1–2 | Intratumoral | 4.5–18 | na | 1–2 days | 37.9 weeks | Cerebral edema, hemiparesis, headache |
Carpentier et al | 2006 | CpG oligonucleotide | I | Recurrent Gr IV GBM (24) | 1–2 | Intratumoral | 1 ml | na | 6 h | 29 weeks | Lymphopenia, worsening of neurologic condition |
Vogelbaum et al | 2007 | IL-13 PE38QQR (Cintredekin besudotox) | I | Newly diagnosed Gr IV GBM (21) & Grade III AO (1) | 2–4 | Peri-resection cavity | 72 | na | 4 days | Survival range 5–113 weeks | Seizure, aphasia, confusion, fatigue, gait disturbance, nystagmus |
Kunwar et al | 2007 | IL-13 PE38QQR (Cintredekin besudotox) | I | Recurrent Gr IV GBM (46) & Gr III AA (3) & Gr III AO (2) | 1–3 | Peri-resection cavity | 72 | 17.9 cm3 ± 12.5 cm3 | 4 days | 42.7 weeks (GBM only); 45.9 weeks all patients | Hemiparesis, convulsions, headache |
Tanner et al | 2007 | Paclitaxel | I/II | Recurrent Gr IV GBM (8) | 1–2 | Intra- and Peri-tumoral | 26 ml | 12.8–22.9 cm^3 | 120 h | survival range 4–15 months | Cerebral edema, neurological deterioration, skin necrosis |
Hau et al | 2007 | AP 12009/Trabedersen (TGF-B2 inhibitor) | I/II | Recurrent Gr IV GBM (19) & Gr III AA (5) | 1 | intratumoral | 23–80.6 ml | na | 4 days, 7 days | 44 weeks (GBM) | Brain edema |
Kunwar et al | 2010 | IL-13 PE38QQR (Cintredekin besudotox) | III | Recurrent Gr IV GBM (296) | 2–4 | Peri-resection cavity | 72 | na | 4 days | 45.3 weeks | Pulmonary embolism |
Carpentier et al | 2010 | CpG oligonucleotide | II | Recurrent Gr IV GBM (34) | 2 | Intratumoral | 2 ml | na | 6 h | 28 weeks | Transient neurological worsening, fever, hemorrhage at catheter site SAEs- infection, pneumoencephaly, hemorrhage |
Bogdahn et al | 2011 | AP 12009/Trabedersen (TGF-B2 inhibitor) | IIB | Recurrent Gr IV GBM (103) & Gr III AA (42) | 1 | Intratumoral | 40 | na | 7 days | 36.4 weeks (GBM only) | Meningitis, hyponatremia, cerebral edema, thrombocytopenia |
Bruce et al | 2011 | Topotecan | IB | Recurrent Gr IV GBM (10) & Gr III glioma (6) | 2 | Intra- and Peri-tumoral | 40–100 | na | 4.17 days | 58.5 weeks (GBM only) | Parietal syndrome, dysmetria, hemineglect, weakness |
Kicielinski et al | 2014 | Reovirus | I | Recurrent Gr IV GBM (12) & AA (3) | 1–4 | Intratumoral | na | na | 72 h | survival 140 days | Catheter clogging, convulsions |
Desjardins et al | 2018 | PVSRIPO | I | Recurrent Gr IV GBM (61) | 1 | Intratumoral | 3.25 ml | na | 6.5 h | 50 weeks | Hemorrhage, headache, hemiparesis, seizure |
Sampson et al | 2023 | MDNA55 (IL4-PE | IIb | Recurrent Gr IV GBM (47) | 1–4 | Intra and Peri-tumoral | Up to 66 mL | Median tumor area coverage = 52.66% | < 48 h | 11.6 months | Seizure, fatigue, headaches, muscular weakness |
Bos et al | 2023 | rhBMP4 | I | Recurrent Gr IV GBM (15) | 3 | Intra and Peri-tumoral | Up to 66 mL | 27.5–125.5 cm^3 | 4–6 days | 7.0 months | Headache, vomiting, hemiparesis, hyperglycemia |
Study | Tracer/Imaging Agent | Time Frame of Imaging | Trial Number | Phase | Status |
---|---|---|---|---|---|
D2C7 for recurrent malignant glioma | N/A | N/A | NCT02303678 | 1/2 | Active, Not Recruiting |
D2C7-IT with atezolizumab for recurrent gliomas | N/A | N/A | NCT04160494 | 1 | Active, Not Recruiting |
PVSRIPO for recurrent GBM | N/A | N/A | NCT01491893 | 2 | Completed |
PVSRIPO and pembrolizumab in patients with recurrent glioblastoma (LUMINOS-101) | N/A | N/A | NCT04479241 | 2 | Active, Not Recruiting |
EGFRvIII CAR T cells for recurrent GBM (INTERCEPT) | 111-Indium-labeled CAR-T cells (SPECT-traceable) | 2 days post-infusion | NCT03283631 | 1 | Closed |
186Rhenium nanoliposomes (186RNL) in recurrent glioma | 186-Rhenium-labeled liposomes (SPECT-traceable) | Up to 7 days post-infusion | NCT01906385 | 1/2 | Recruiting |
Topotecan via CED for recurrent grade III/IV glioma | Gadolinium-based agent | Real-time | NCT03927274 | 1 | Terminated (Lack of funding) |
Nanoliposomal irinotecan for recurrent high-grade glioma | Gadolinium-based agent | Within 2 days post-infusion | NCT02022644 | 1 | Completed |
Convection-enhanced delivery of OS2966 for patients with high-grade glioma undergoing a surgical resection | Gadoteridol | Within 1 day post-infusion | NCT04608812 | 1 | Terminated (Enrollment) |
Safety & Efficacy/Tolerability of Rhenium-186 NanoLiposomes (186RNL) for Patients Who Received a Prior 186RNL Treatment | 186-Rhenium-labeled liposomes (SPECT-traceable) | 3 days post-infusion | NCT05460507 | 1 | Not yet recruiting |
D2C7-IT in Combination With 2141-V11 for Recurrent Malignant Glioma | N/A | N/A | NCT04547777 | 1 | Recruiting |