Clinical trial NCT02915523
Conditions: Epithelial Ovarian Cancer Peritoneal Cancer Fallopian Tube Cancer
Keywords: Ovarian Cancer Histone Deacetylase Inhibitors Entinostat Solid tumor Avelumab SNDX-275 Ovarian Neoplasms Ovarian Diseases Fallopian Tube Cancer Peritoneal Cancer
Sponsor: Syndax Pharmaceuticals
Start date: 2016-12-19; Completion date: 2021-04-21
Enrollment: 140 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to determine the biologically active dose of entinostat, when given in combination with avelumab, that is safe and warrants further investigation. Additionally, this study will evaluate the effectiveness of entinostat in combination with avelumab at the determined dose in terms of progression free survival compared to avelumab plus placebo in participants with refractory or recurrent epithelial ovarian cancer.

Detailed description:
The study is comprised of 2 phases: an open-label Safety Lead-in (Phase 1b) followed by an Expansion Phase (Phase 2). The Expansion Phase will evaluate the efficacy and safety of entinostat with avelumab when administered at the Recommended Phase 2 Dose (RP2D) versus avelumab alone in participants with advanced epithelial ovarian cancer in a randomized, double-blind, placebo-controlled setting. In Phase 2, participants will be randomized in a 2:1 ratio to receive avelumab plus entinostat or avelumab plus placebo, respectively.

All participants will be assessed at Screening and at specified times during the conduct of the study using standard clinical and laboratory assessments. Participants will be assessed for response through radiological assessments. Participants will continue receiving their appropriate cycles of study treatment until tumor progression or adverse events (AEs) occur which necessitate discontinuing therapy as determined by the Investigator.

Arms: arm 1: Avelumab is administered intravenously (IV) on Day 1 of each 14-day cycle in combination with Entinostat administration on Day 1 and Day 8 of each cycle at the Maximum tolerated Dose (MTD)/RP2D as determined in the Phase Ib (Dose Determination) part of the study. arm 2: Avelumab is administered intravenously (IV) on Day 1 of each 14-day cycle in combination with placebo administered on Day 1 and Day 8 of each cycle.
Interventions: intervention 1: entinostat intervention 2: avelumab intervention 3: Placebo
Intervention descriptions: intervention 1: An orally available histone deacetylases inhibitor (HDACi). intervention 2: A fully human antibody of the immunoglobulin (Ig) G1 isotype that targets and blocks Programmed death-ligand 1 (PD-L1), the ligand for Programmed cell death protein 1 (PD-1) receptor. intervention 3: A pill containing no active drug ingredient.

Protocol documents:
Prot_000.pdf: 
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` &'&%&%#'(	#$%	+'&%$	```````````````````````````````````````````````````````````````````````````	
	
/<1/
IFE[Q5I6j5=K96EF96DG11111111111111111111111111111111111111111111111111111111111111111111111111111111111111111/2/
/<1/1/
A8FK5/VkYDK5Y595BE6GF96DGA8FK5l111111111111111111111111111111111111111111111111/2/


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/01/12	
45678	2	9:;<6=7>?=	45678@	
111111111111111111111111111111111111111111111111111111111111111111	
/2/	
/012	 45678	2	A=B8C>D	:EE>F6FG	H=6IG787	11111111111111111111111111111111111111111111111111111111111111111111111	
/20	
/010	 4?<JI6B>?=7	E?C	H=6IG7>7	
111111111111111111111111111111111111111111111111111111111111111111111111111111111111111	
/20	
/01K	 LBJMG	:=M<?>=B7	
1111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111	
/2K	
/01N	 LB6B>7B>F6I	O8B5?M7	
111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111	
/2N	
/01N1/	
P8=8C6I	
111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111	
/2N	
/01N12	
46B>8=B	Q>7<?7>B>?=	
111111111111111111111111111111111111111111111111111111111111111111111111111111	
/2N	
/01N10	
Q8D?RC6<5>F7	6=M	S56C6FB8C>7B>F7	
111111111111111111111111111111111111111111111111111111	
/2N	
/01N1K	
:;B8=B	?E	:;<?7JC8	
111111111111111111111111111111111111111111111111111111111111111111111111111111	
/2T	
/01N1N	
:EE>F6FG	H=6IG787	
11111111111111111111111111111111111111111111111111111111111111111111111111111111	
/2T	
/01N1T	
L6E8BG	H=6IG787	
11111111111111111111111111111111111111111111111111111111111111111111111111111111111	
/2U	
/01N1V	
456CD6F?W>=8B>F	6=M	H=B>MCJR	H=B>X?MG	H=6IG787	
1111111111111111111111111111	
/0/	
/01N1Y	
S?CC8I6B>Z8	H=6IG787	
111111111111111111111111111111111111111111111111111111111111111111111111111	
/0/	
[\ +	]-('&$+)	$^(%]'&%$	
\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\	
	
/K1/	 A=E?CD8M	S?=78=B	
11111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111	
/02	
/K12	 A=7B>BJB>?=6I	_8Z>8`	a?6CMb:B5>F7	S?DD>BB88	
111111111111111111111111111111111111111111111111111111	
/02	
/K10	 4C8c7BJMG	Q?FJD8=B6B>?=	_8dJ>C8D8=B7	
111111111111111111111111111111111111111111111111111111111111111	
/00	
/K1K	 46B>8=B	S?=E>M8=B>6I>BG	111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111	
/00	
\ ',%%&+'&%e		'	(	]'(	$^(%]'&%$	
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	
/N1/	 4C?B?F?I	HD8=MD8=B7	6=M	LBJMG	f8CD>=6B>?=	
11111111111111111111111111111111111111111111111111111	
/0N	
/N12	 LBJMG	Q?FJD8=B6B>?=	6=M	HCF5>Z8	
11111111111111111111111111111111111111111111111111111111111111111111111	
/0N	
/N10	 LBJMG	O?=>B?C>=R	6=M	Q6B6	S?II8FB>?=	
11111111111111111111111111111111111111111111111111111111111111111	
/0T	
\ +		+	#		
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012345657		89:4;<34	=>	8?<;@	ABB4BBC4D?B	7777777777777777777777777777777777777777777777777777777777777777777777777777777777	GH	
01234I657		J49KBK=D	L<34B	>=M	N1?K4D?	ODM=33C4D?	PBKDQ	?:4	L=33KDQ	8KR	J4BKQD	
777777777777777777777777	ST	
01234U657		V=D6:4C1?=3=QK9	0=RK9K?@W	J=B4	X=;K>K91?K=DB	>=M	OD?KD=B?1?	
7777777777777777777777777777777777	TI	
01234U6G7		Y4C1?=3=QK9	0=RK9K?@W		J=B4	X=;K>K91?K=D	>=M	OD?KD=B?1?	
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7777777777777777777777777777777777777	EG	
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77777777777777777777777777777777777777777777777777777777777777777	US	
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77777777777777777777777777777777777777777777777777777777777777777777777777777	55^	
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777777777777777777777777777777777777777777777777777777777777777777777777	55U	
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77777777777777777777777777777777	5^T	
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777777777777777777777777777777777777777777777777777777777777777777777777777777777777	5^E	
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77777777777777777777777777777777777777777777777777777777777777777777777777777777777777777777777777777777777777	ZS	
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	
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	
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=''
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	
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	 !"#$!%
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! 0	- 
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31 	& '
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4+&'	 
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6
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'
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	
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 
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.''
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	
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.1 	 		8
# 1  .28
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1  
	   2 
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 
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
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	
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2 3&	 1,)	#
!'
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43 	 	.) 
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
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.*5
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!!	
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