Trial Watch: Proteasomal inhibitors for anticancer therapy

Figures & data

Table 1. Completed clinical trials testing the therapeutic profile of bortezomib in cancer patients.

Indication(s)	Phase	Notes	Ref.
Biliary tract cancers	II	As single agent	326
Breast cancer	II	Combined with doxorubicine	331
Follicular lymphoma	II	As single agent	247
		Combined with bendamustine and rituximab	307
Gastric or gastroesophageal carcinoma	I	Combined with epirubicin, carboplatin and capecitabine	315
	II	As single agent	324
Glioblastoma multiforme	II	Combined with vorinostat	329
Hepatocellular carcinoma	II	As single agent	325
		Combined with doxorubicine	333
Head and neck cancer	I	Combined with cisplatin-based chemoradiotherapy	318
	II	As single agent or combined with irinotecan	328
		Combined with doxorubicine	327
Hematologic neoplasms	I	Combined with doxorubicin	264
	I/II	Combined with chemotherapy and HSCT	311
		Combined with gemcitabine	312
		Combined with R-CHOP	308
Melanoma and soft tissue sarcoma	I	Combined with dacarbazine	321
Mesothelioma	II	Combined with cisplatin	330
Mantle cell lymphoma	II	As single agent	83,84
		Combined with gemcitabine	297
Myelodysplastic syndrome	I/II	Combined with cytarabine	300
	I	As single agent	227–229
	Ib	Combined with panobinostat and dexamethasone	269
	I/II	Combined with bendamustine, rituximab and dexamethasone	286
		Combined with doxorubicin and dexamethasone	266
		Combined with fotemustine and dexamethasone	292
		Combined with melphalan and prednisone	241,243
	II	As single agent	78,79,97,251
		Combined with bendamustine and rituximab	284,285
		Combined with bevacizumab	287
		Combined with dexamethasone	252,254
		Combined with dexamethasone and DLIs	255
		Combined with doxorubicin	263
		Combined with doxorubicin and dexamethasone	265,267
		Combined with fludarabine and melphalan prior to HSCT	295
		Combined with lenalidomide and dexamethasone	278
		Combined with melphalan, lenalidomide, and HSCT	296.
		Combined with melphalan, prednisone, and siltuximab	239
		Combined with panobinostat and dexamethasone	270
		Combined with thalidomide, dexamethasone, and cyclophosphamide	277
	III	As single agent	98,234
		Combined with melphalan and prednisone	237,238,240,242
		Combined with melphalan- and prednisone-based chemotherapy	240,245
		Combined with melphalan and prednisone or thalidomide and prednisone	240,244,246
		Combined with thalidomide and dexamethasone	276
		Combined with vorinostat	268
	IIIb	As single agent or combined with dexamethasone	253
Non-Hodgkin's lymphoma	I	Combined with ^90Y-ibritumomab tiuxetan	303
	II	Combined with rituximab and dexamethasone	306
Non-small cell lung carcinoma	I	Combined with vorinostat and consolidative surgery	322
	II	As single agent	323
		Combined with vorinostat	332
Ovarian carcinoma	II	Combined with doxorubicine	337
Prostate carcinoma	II	Combined with prednisone	334
		Combined with docetaxel	336
Advanced solid tumors	I	Combined with oxaliplatin	320
		Combined with sorafenib	314
		Combined with sunitinib	317
		Combined with tanespimycin	316
		Combined with vorinostat	313,319

Abbreviations: DLI, donor lymphocyte infusion; HSCT, hematopoietic stem cell transplantation; R-CHOP, rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone.

Table 2. Ongoing clinical trials recently launched to evaluate the safety and efficacy of off-label bortezomib in cancer patients.*

Indication(s)	Phase	Status	Notes	Ref.
Acute lymphoblastic leukemia	II	Recruiting	Combined with doxorubicin-based radiotherapy	NCT01769209
Acute myeloid leukemia	I	Recruiting	Combined with decitabine and sorafenib	NCT01861314
	I/II	Recruiting	Combined with sorafenib and vorinostat	NCT01534260
	II	Recruiting	Combined with arsenic trioxide	NCT01950611
			Combined with liposomal doxorubicin	NCT01736943
Diffuse large B-cell lymphoma	II	Recruiting	As single agent	NCT01965977
			Combined with rituximab, cyclophosphamide, doxorubicin, and prednisone	NCT01848132
	II/III	Recruiting	Combined with rituximab-based chemotherapy prior to HSCT	NCT01805557
Hematologic neoplasms	I	Recruiting	Combined with alisertib and rituximab	NCT01695941
	III	Not yet recruiting	Combined with cyclophosphamide- and doxorubicin-based chemoradiotherapy	NCT02112916
Myelodysplastic syndrome	II	Recruiting	As single agent	NCT01891968
Neuroblastoma	I/II	Recruiting	Combined with eflornithine	NCT02139397
Non-small cell lung carcinoma	II	Recruiting	Combined with acyclovir	NCT01833143
Waldenström's macroglobulinemia	II	Recruiting	Combined with cyclophosphamide, dexamethasone, and rituximab	NCT01788020
	III	Recruiting	Combined with cyclophosphamide, fludarabine, and rituximab	NCT01592981

Abbreviation: HSCT, hematopoietic stem cell transplantation.

*initiated after January 1 2012 and not terminated, suspended, withdrawn, or completed at the date of submission.

Table 3. Completed clinical trials testing the therapeutic profile of carfilzomib in cancer patients.

Indication(s)	Phase	Notes	Ref.
Multiple myeloma	I	As single agent	384,385
	Ib	Combined with dexamethasone and lenalidomide	389
	I/II	Combined with a panel of chemotherapeutics	392
		Combined with dexamethasone and lenalidomide	391
	II	As single agent	85–88,387
		Combined with dexamethasone and lenalidomide	390
		Combined with dexamethasone and cyclophosphamide	393
	III	As single agent	394
Advanced solid tumors	I/II	As single agent	395

Table 4. Ongoing clinical trials recently launched to evaluate the safety and efficacy of off-label carfilzomib in cancer patients.*

Indication(s)	Phase	Status	Notes	Ref.
Diffuse large B-cell lymphoma	I/II	Not yet recruiting	Combined with rituximab and CHOP	NCT02073097
		Recruiting	Combined with rituximab, ifosfamide, carboplatin, and etoposide	NCT01959698
Hematological neoplasms	I	Recruiting	Combined with dexamethasone and HSCT	NCT01926665
Mantle cell lymphoma	I/II	Recruiting	Combined with lenalidomide and rituximab	NCT01729104
	II	Not yet recruiting	As single agent	NCT02042950
Non-Hodgkin's lymphoma	I	Not yet recruiting	Combined with belinostat	NCT02142530
			Combined with bendamustine and rituximab	NCT02187133
Prostate carcinoma	II	Recruiting	Combined with dexamethasone and acyclovir	NCT02047253
Renal cell carcinoma	II	Active, not recruiting	As single agent	NCT01775930
Small cell lung carcinoma	I/II	Recruiting	Combined with carboplatin and etoposide	NCT01987232
T-cell lymphoma	I	Recruiting	Combined with romidepsin	NCT01738594
Waldenström's macroglobulinemia	II	Recruiting	Combined with dexamethasone and rituximab	NCT01813227
Advanced tumors	I	Recruiting	As single agent	NCT01949545
	I/II	Recruiting	Combined with irinotecan	NCT01941316

Abbreviations: CHOP, cyclophosphamide, doxorubicin, vincristine, and prednisone; HSCT, hematopoietic stem cell transplantation.

*initiated after January 1 2012 and not terminated, suspended, withdrawn, or completed at the date of submission.

Table 5. Clinical trials recently launched to evaluate the safety and efficacy of third-generation proteasomal inhibitors in cancer patients.*

Inhibitor	Indication(s)	Phase	Status	Notes	Ref.
Ixazomib	Acute myeloid leukemia	I	Not yet recruiting	Combined with cytarabine, etoposide, and mitoxantrone	NCT02070458
		II	Recruiting	As single agent	NCT02030405
	Follicular lymphoma	II	Recruiting	As single agent	NCT01939899
	Hematologic neoplasms	I	Recruiting	Combined with doxorubicin-based chemotherapy	NCT01887587
		II	Not yet recruiting	As single agent after HSCT	NCT02169791
	Multiple myeloma	I	Recruiting	Combined with dexamethasone and lenalidomide	NCT01645930
				Combined with dexamethasone	NCT01830816
				Combined with dexamethasone and panobinostat	NCT02057640
		I/II	Not yet recruiting	Combined with dexamethasone and pomalidomide	NCT02119468
			Recruiting	Combined with dexamethasone and cyclophosphamide	NCT01864018
				Combined with dexamethasone and pomalidomide	NCT02004275
		II	Not yet recruiting	As single agent after HSCT	NCT02168101
				Combined with dexamethasone and lenalidomide	NCT01936532
			Recruiting	Combined with dexamethasone	NCT01415882
				Combined with lenalidomide after HSCT	NCT01718743
				Combined with dexamethasone and cyclophosphamide	NCT02046070
		III	Not yet recruiting	As single agent after HSCT	NCT02181413
		III	Recruiting	Combined with dexamethasone and lenalidomide	NCT01564537
					NCT01850524
	T-cell lymphoma	II	Not yet recruiting	As single agent	NCT02158975
	Advanced tumors	I	Not yet recruiting	Combined with vorinostat	NCT02042989
			Recruiting	As single agent	NCT01912222
					NCT01953783
Marizomib	Multiple myeloma	I	Recruiting	Combined with dexamethasone and pomalidomide	NCT02103335
		I/II	Recruiting	As single agent	NCT00461045
Oprozomib	Multiple myeloma	I/II	Recruiting	Combined with dexamethasone and lenalidomide or cyclophosphamide	NCT01881789
				Combined with dexamethasone	NCT01832727
				Combined with dexamethasone and pomalidomide	NCT01999335
				Combined with melphalan and prednisone	NCT02072863

Abbreviations: HSCT, hematopoietic stem cell transplantation.

*initiated after January 1 2012 and not terminated, suspended, withdrawn, or completed at the date of submission.