Table 1:
Select clinical trials evaluating systemic therapies for patients with BM
| NCT (Phase) | Inclusion / exclusion criteria | Planned Enrollment | Intervention | Study Design | Primary Outcome |
|---|---|---|---|---|---|
| Targeted Therapy | |||||
| NCT04992013 / (2) | CNS basket trial; presence of progressive BM and BRCA1, BRCA2, PARP, DNA repair pathway, or homologous recombination gene alteration within BM | 20 | Niraparib | Single arm open-label | Intracranial clinical benefit rate |
| NCT03994796 / (1/2) | CNS basket trial; presence of progressive BM and CDK pathway, PI3K pathway, or NTRK/ROS1 alteration within BM | 150 | Abemaciclib Paxalisib Entrectinib |
Non-randomized open-label parallel assignment: Arm 1: CDK pathway alteration Arm 2: PI3K pathway alteration Arm 3: NTRK/ROS1 alteration |
Intracranial clinical benefit rate |
| NCT02896335 / 2 | CNS basket trial; presence of progressive BM and CDK pathway alteration within BM | 30 | Palbociclib | Single arm open-label | Intracranial clinical benefit rate |
| NCT03898908 / 2 | BRAF-mutant metastatic melanoma without prior local treatment in the brain | 38 | Encorafenib / binimetinib | Non-randomized open-label parallel assisgnment: Arm 1: asymptomatic BM Arm 2: symptomatic BM |
Intracranial response rate |
| NCT04158947 / 1/2 | HER-2 positive breast cancer BM | 130 | Afatinib and trastuzumab emtansine (T-DM1) | Randomized two-arm study: Arm 1 – T-DM1 + afatinib in dose escalation Arm 2 – T-DM1 + afatinib vs. T-DM1 |
Maximum tolerated dose of afatinib when used in combination with T-DM1; intracranial response rate |
| NCT04752059 / 2 | HER-2 positive breast cancer BM | 15 | Trastuzumab deruxtecan (T-DxD) | Single arm open-label | Intracranial response rate |
| NCT04185883 / 1b/2 | Basket trial for KRAS G12C-mutant solid tumors (progressive BM are allowed) | 1054 | Sotorasib and histology-specific therapeutic | Non-randomized, open-label, multi-arm (for each histology) | Maximum tolerated dose of sotorasib in combination with other therapeutics; extracranial response rate |
| Astrocyte-directed Therapy | |||||
| NCT01904123 / 1 | Progressive melanoma BM or glioma | 8 | WP1066 (STAT3 inhibitor) | Single arm open-label | Maximum tolerated dose; incidence of adverse events |
| NCT02429570 / pilot | Progressive BM of any histology | 30 | Meclofenamate (CX-43 inhibitor) | Single arm open-label | Feasibility |
| Chemotherapy (prevention trial) | |||||
| NCT03190967 / 1/2 | Histology-confirmed HER-2 positive breast cancer BM | 125 | T-DM1 Temozolomide (TMZ) |
Randomized open-label sequential assignment Arm 1 – T-DM1 + TMZ in dose escalation Arm 2 – T-DM1 alone |
Median time to developing new BM; maximum tolerated dose of TMZ when used in combination with T-DM1; |
| Combination immunotherapy regimens | |||||
| NCT04789668 / 1/2 | Progressive BM of any histology | 36 | Bintrafusp alfa + pimasertib | Single arm open-label | Intracranial clinical benefit rate; incidence of dose-limiting toxicities |
| NCT03175432 / 2 | BRAF V600 wild type melanoma BM | 60 | Atezolizumab Bevacizumab Cobimetinib |
Non-randomized open-label parallel assignment Arm 1: atezolizumab, bevacizumab Arm 2: atezolizumab, bevacizumab, cobimetinib |
Intracranial response rate |
| NCT03131908 / 1/2 | Metastatic melanoma with PTEN loss (progressive BM can be enrolled) | 36 | GSK2636771 (PI3K inhibitor) Pembrolizumab |
Single arm open-label | Maximum tolerated dose of GSK2636771 in combination with pembrolizumab; extracranial and intracranial response rate |
| NCT02910700 / 2 | BRAF V600 mutant metastatic melanoma that has progressed on prior PD-1 inhibition (progressive BM can be enrolled) | 51 | Binimetinib Dabrafenib Encorafenib Trametinib Nivolumab |
Non-randomized open-label parallel assignment Arm 1 – nivolumab, dabrafenib Arm 2 – nivolumab, trametinib Arm 3 – nivolumab, encorafenib, binimetinib |
Extracranial and intracranial response rate |
| NCT02886585 / 2 | CNS metastasis of any histology Arm 1 – untreated BM Arm 2 – progressive BM Arm 3 – neoplastic meningitis Arm 4 – 1–4 melanoma BM |
102 | Pembrolizumab Stereotactic radiosurgery |
Non-randomized open-label parallel assignment Arm 1, 2, 3 – pembrolizumab Arm 4 – pembrolizumab + SRS |
Intracranial response rate |
| NCT02816021 / 2 | Metastatic melanoma (progressive BM can be enrolled) Arm 1 – PD-1 naïve Arm 2 – post PD-1 progression |
24 | Azacitidine Pembrolizumab |
Non-randomized open-label parallel assignment | Extracranial and intracranial response rate |
| CAR T-cell therapy | |||||
| NCT03696030 / 1 | CNS metastasis of any histology with HER2-overexpression | 39 | CAR T cell targeting HER2 antigen | Single arm open-label | Treatment-related adverse events |
| Dendritic cell vaccine | |||||
| NCT04348747 / 2 | Triple-negative or HER-2 positive breast cancer BM | 23 | Anti-HER2 / HER3 dendritic cell vaccine | Single arm open-label | Intracranial response rate |