NCT00926640

A Phase I Study of Belinostat in Combination With Cisplatin and Etoposide in Adults With Small Cell Lung Carcinoma and Other Advanced Cancers

Completed Phase 1 Last updated 19 October 2018

What this trial tests

Phase 1 trial testing Belinostat in Carcinoma Neuroendocrine in 28 participants. Completed in 20 April 2018.

Timeline

1 July 2009

Primary endpoint
16 June 2017

20 April 2018

Quick facts

Lead sponsor	National Cancer Institute (NCI)
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	28
Start date	1 July 2009
Primary completion	16 June 2017
Estimated completion	20 April 2018
Sites	1 location across United States

Drugs / interventions tested

• Belinostat (belinostat) — full drug profile →
• Cisplatin (cisplatin) — full drug profile →
• Etoposide (etoposide) — full drug profile →

Conditions studied

• Carcinoma Neuroendocrine — all drugs for Carcinoma Neuroendocrine →
• Small Cell Lung Carcinoma — all drugs for Small Cell Lung Carcinoma →
• Malignant Epithelial Neoplasms — all drugs for Malignant Epithelial Neoplasms →

Sponsor

National Cancer Institute (NCI)

Who can join

Adults 18 to 99, any sex, with Carcinoma Neuroendocrine or Small Cell Lung Carcinoma. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

BACKGROUND:

* The histone deacetylase (HDAC) inhibitors are a novel class of anticancer agent. These agents lead to the increased acetylation of both histone and non-histone proteins, which leads to rapid cell death in many tumor models. It is thought that the cell death observed with this class of agents may be mediated, in part, through the selective acetylation of histone proteins resulting in increased expression of specific genes.
* For solid tumors in general, cell death in preclinical models has not translated to activity in patients. For this reason, studies increasingly have combined chemotherapy with HDAC inhibitors to achieve additive and potentially synergistic effects on cancer cells.
* This protocol will study a continuous infusion of the HDAC inhibitor belinostat in combination with cisplatin and etoposide for patients with advanced cancer.

OBJECTIVES:

* To determine a safe and tolerable phase 2 dose for the combination of belinostat with cisplatin and etoposide.
* Evaluate molecular markers of HDAC inhibition.

ELIGIBILITY:

* The protocol will be open to all patients with recurrent or advanced cancer (small-cell lung cancer and other advanced cancers) for whom standard therapy offers no curative potential.
* Age greater than or equal to 18 years
* ECOG Performance Status 0-2

DESIGN:

* The study will begin with belinostat 400 mg/m (2)/24h administered by continuous IV infusion on days 1 and 2, cisplatin at 80 mg/m (2) IV on day 2, and etoposide at 100 mg/m (2) IV daily times 3 on days 2 - 4. Dose escalation of belinostat will follow according to traditional 3 patient cohorts.
* Treatment schedule and dose escalation schemata.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Central role of Snail1 in the regulation of EMT and resistance in cancer: a target for therapeutic intervention.
   Kaufhold S, Bonavida B. · · 2014 · cited 342× · PMID 25084828 · DOI 10.1186/s13046-014-0062-0
2. The Roles of Histone Deacetylases and Their Inhibitors in Cancer Therapy.
   Li G, Tian Y, Zhu WG. · · 2020 · cited 246× · PMID 33117804 · DOI 10.3389/fcell.2020.576946
3. Small cell lung cancer: will recent progress lead to improved outcomes?
   Pietanza MC, Byers LA, Minna JD, Rudin CM. · · 2015 · cited 176× · PMID 25979931 · DOI 10.1158/1078-0432.ccr-14-2958
4. Synergistic Enhancement of Cancer Therapy Using HDAC Inhibitors: Opportunity for Clinical Trials.
   Hontecillas-Prieto L, Flores-Campos R, Silver A, de Álava E, et al · · 2020 · cited 145× · PMID 33024443 · DOI 10.3389/fgene.2020.578011
5. Regulation and signaling pathways in cancer stem cells: implications for targeted therapy for cancer.
   Zeng Z, Fu M, Hu Y, Wei Y, et al · · 2023 · cited 93× · PMID 37853437 · DOI 10.1186/s12943-023-01877-w
6. Targeting Histone Deacetylases in Diseases: Where Are We?
   Benedetti R, Conte M, Altucci L. · · 2015 · cited 91× · PMID 24382114 · DOI 10.1089/ars.2013.5776
7. Advances in epigenetic therapeutics with focus on solid tumors.
   Jin N, George TL, Otterson GA, Verschraegen C, et al · · 2021 · cited 87× · PMID 33879235 · DOI 10.1186/s13148-021-01069-7
8. Histone deacetylases in skeletal development and bone mass maintenance.
   McGee-Lawrence ME, Westendorf JJ. · · 2011 · cited 80× · PMID 21185361 · DOI 10.1016/j.gene.2010.12.003