NCT01664000

A Phase 1, Open-Label, Dose-Escalation, Safety, Pharmacokinetic and Pharmacodynamic Study of Kevetrin (Thioureidobutyronitrile) Administered Intravenously, in Patients With Advanced Solid Tumors

Completed Phase 1 Last updated 23 February 2016

What this trial tests

Phase 1 trial testing thioureidobutyronitrile in Solid Tumors in 48 participants. Completed in 1 February 2016.

Timeline

1 October 2012

Primary endpoint
1 January 2016

1 February 2016

Quick facts

Lead sponsor	Cellceutix Corporation
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	48
Start date	1 October 2012
Primary completion	1 January 2016
Estimated completion	1 February 2016
Sites	1 location across United States

Drugs / interventions tested

• thioureidobutyronitrile — full drug profile →

Conditions studied

• Solid Tumors — all drugs for Solid Tumors →

Sponsor

Cellceutix Corporation — full company profile →

Who can join

18 and older, any sex, with Solid Tumors. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Maximum Tolerated Dose (MTD) of Kevetrin
  Time frame: up to 6 months
  A dose will be declared the MTD if at least 1 patient out of 6 patients experience a dose limiting toxicity (DLT) at the highest dose level below the maximally administered dose. Once an MTD has been established, up to 12 additional patients may be enrolled at the MTD dose level for confirmation of safety. The maximally administered dose is if 1 or more of 6 patients experience a DLT.
• Dose Limiting Toxicities (DLT) of Kevetrin.
  Time frame: up to 4 weeks
  The definition of dose limiting toxicity (DLT) is in accord with the NCI Common Terminology Criteria for Adverse Events v4.0 (CTCAE). Dose limiting toxicity will be defined as: * Grade 3 or 4 neutropenia complicated by fever, or greater than 38.5°C documented infection, or Grade 4 neutropenia of greater than 7 days duration * Grade 4 thrombocytopenia or grade 3 thrombocytopenia complicated by hem

Sponsor's own description

In the laboratory, Kevetrin activates p53, a tumor suppressor protein that has an important role in protecting the body. p53 functions by activating proteins that repair DNA and kill cells that have genetic mutations such as in cancers. Research experiments showed that when cancer cells were treated with Kevetrin, it activated p53 which induced p21, a protein that inhibits cancer cell growth. p53 also induced PUMA (p53 up-regulated modulator of apoptosis), a protein that causes tumor cell death. Because of these activities, slowing cancer cell growth and causing cancer cell death, Kevetrin may help to treat tumors.

Publications & conference data

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

1. The Role of p53 Signaling in Colorectal Cancer.
   Liebl MC, Hofmann TG. · · 2021 · cited 231× · PMID 33924934 · DOI 10.3390/cancers13092125
2. Prospective comprehensive genomic profiling of advanced gastric carcinoma cases reveals frequent clinically relevant genomic alterations and new routes for targeted therapies.
   Ali SM, Sanford EM, Klempner SJ, Rubinson DA, et al · · 2015 · cited 61× · PMID 25882375 · DOI 10.1634/theoncologist.2014-0378
3. Discussion of some 'knowns' and some 'unknowns' about the tumour suppressor p53.
   Lieschke E, Wang Z, Kelly GL, Strasser A. · · 2019 · cited 19× · PMID 30496435 · DOI 10.1093/jmcb/mjy077
4. Kevetrin induces apoptosis in TP53 wild‑type and mutant acute myeloid leukemia cells.
   Napolitano R, De Matteis S, Carloni S, Bruno S, et al · · 2020 · cited 15× · PMID 32945487 · DOI 10.3892/or.2020.7730
5. Adenosine triphosphate induced cell death: Mechanisms and implications in cancer biology and therapy.
   Zhang HL, Sandai D, Zhang ZW, Song ZJ, et al · · 2023 · cited 11× · PMID 38179405 · DOI 10.5306/wjco.v14.i12.549
6. Therapeutic Strategies Targeting Tumor Suppressor Genes in Pancreatic Cancer.
   Kuo KK, Hsiao PJ, Chang WT, Chuang SC, et al · · 2021 · cited 10× · PMID 34359820 · DOI 10.3390/cancers13153920
7. State of the Art of Pharmacological Activators of p53 in Ocular Malignancies.
   Casciano F, Zauli E, Busin M, Caruso L, et al · · 2023 · cited 6× · PMID 37509256 · DOI 10.3390/cancers15143593