Phase 2 Study of ONC201 in Neuroendocrine Tumors

NCT03034200 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: CASE2716
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to learn if a new drug, ONC201 can make tumors become smaller or go away completely. Investigators also want to learn if ONC201 can prevent new deposits of cancer from appearing in new places in participants (metastases). A phase 2 study of ONC201 in PC-PG (pheochromocytoma-paraganglioma) and other neuroendocrine tumors will determine whether inhibition of DRD2 (a member of the dopamine receptor family) is safe in unresectable, recurrent, locally advanced, refractory, or metastatic neuroendocrine cancers including PC-PG, desmoplastic small round cell tumor (DSRCT), Ewing sarcoma (PNET) or any other neuroendicrine tumor with a catecholamine or dopamine biomarker or autocrine or paracrine dependence on dopamine including cholangiocarcinoma and adrenal cortical carcinoma. ONC201 is an investigational (experimental) agent and has a favorable safety profile in phase 1 and early phase 2 clinical trials in advanced cancers. This study design has been chosen to see whether ONC201 is associated with reduction of anti-hypertension medications, safety and significant efficacy against neuroendocrine tumors, especially PC-PG.

Conditions

Recurrent Neuroendocrine Tumor; Metastatic Neuroendocrine Tumor

Keywords

Pheochromocytoma-paraganglioma; ONC201

Outcome Measures

Primary Outcomes (1)

• Tumor Response According to RECIST Criteria

  Complete Response (CR) Disappearance or fibrosis of all target lesions. Any pathologic lymph nodes must have reduction in short axis to \<10mm and standardized uptake value (SUV) is \<4. Partial Response (PR) At least 30% decrease in sum of longest diameters of target lesions (compared to initial on study baseline) and any decrease in SUV in Fludeoxyglucose 18F (18FDG) imaging Stable disease (SD) 0-29% decrease in sum of longest diameters of target lesions (compared to initial on study baseline) or 0-19% increase in sum of longest diameters of target lesions (compared to initial on study baseline). SUV may increase or decrease Progressive disease 20% or more increase of sum of longest diameters of target lesions (compared to initial on study baseline). The sum must also be at an increase of at least 5mm or one or more new lesions that are considered metastatic disease

  Up to 1 Year

Secondary Outcomes (2)

• Median Duration of Therapy

  Up to 5 years

• Overall Survival

  Up to 1 Year

Study Arms (3)

Arm A: Metastatic PC-PG

EXPERIMENTAL

625mg ONC201 will be given once weekly

Drug: ONC201

Arm B: Other NETs

EXPERIMENTAL

625mg ONC201 will be given once weekly

Drug: ONC201

Arm C: PC-PG + other NETs

EXPERIMENTAL

625mg ONC201 will be given on day 1 and day 2 of each week

Drug: ONC201

Interventions

ONC201 DRUG

625mg ONC201 will be given on two consecutive days each week

Arm A: Metastatic PC-PG; Arm B: Other NETs; Arm C: PC-PG + other NETs

Eligibility Criteria

• Age: 14 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

1. "Subjects must have a unresectable, recurrent, locally advanced, refractory, or metastatic neuroendocrine tumor including pheochromocytoma-paraganglioma (PC-PG), DSRCT, Ewing Sarcoma or PNET, or any neuroendocrine tumor with a catecholamine or dopamine biomarker or autocrine or paracrine dependence on dopamine including cholangiocarcinoma and adrenal cortical carcinoma (ACC). 2. There is no limit on number of prior therapies. 3. Age ≥14 years. 4. Subjects must have normal organ and marrow function as defined below. Studies should be done within 3 weeks prior to enrollment * Hemoglobin ≥ 10.0 g/dl * Leukocytes ≥ 1500/mcL * Absolute neutrophil count ≥ 1,000/mcL * Platelet count ≥ 75000/mcL * Total bilirubin within 1.5 x normal institutional limits * AST (SGOT) ≤ 5 X institutional upper limit of normal * ALT (SGPT) ≤ 5 X institutional upper limit of normal * Serum Creatinine \<3.0mg/dL * 5 1 lesion detectable on CT, MRI, 18FDG PET-CT 6 Subjects must have the ability to understand and the willingness to sign a written informed consent document. 7: Karnofsky or if \<16 years old Lansky Play Performance status ≥ 60%

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Peter Anderson: lead

Study Sites (1)

Cleveland Clinic Pediatric and Taussig Cancer Institute, Case Comprehensive Cancer Center

Cleveland, Ohio, 44195, United States

Location

Related Publications (8)

• Allen JE, Krigsfeld G, Mayes PA, Patel L, Dicker DT, Patel AS, Dolloff NG, Messaris E, Scata KA, Wang W, Zhou JY, Wu GS, El-Deiry WS. Dual inactivation of Akt and ERK by TIC10 signals Foxo3a nuclear translocation, TRAIL gene induction, and potent antitumor effects. Sci Transl Med. 2013 Feb 6;5(171):171ra17. doi: 10.1126/scitranslmed.3004828.

  PMID: 23390247 BACKGROUND

• Allen JE, Krigsfeld G, Patel L, Mayes PA, Dicker DT, Wu GS, El-Deiry WS. Identification of TRAIL-inducing compounds highlights small molecule ONC201/TIC10 as a unique anti-cancer agent that activates the TRAIL pathway. Mol Cancer. 2015 May 1;14:99. doi: 10.1186/s12943-015-0346-9.

  PMID: 25927855 BACKGROUND

• Allen JE, Prabhu VV, Talekar M, van den Heuvel AP, Lim B, Dicker DT, Fritz JL, Beck A, El-Deiry WS. Genetic and Pharmacological Screens Converge in Identifying FLIP, BCL2, and IAP Proteins as Key Regulators of Sensitivity to the TRAIL-Inducing Anticancer Agent ONC201/TIC10. Cancer Res. 2015 Apr 15;75(8):1668-74. doi: 10.1158/0008-5472.CAN-14-2356. Epub 2015 Feb 13.

  PMID: 25681273 BACKGROUND

• Allen JE, Kline CL, Prabhu VV, Wagner J, Ishizawa J, Madhukar N, Lev A, Baumeister M, Zhou L, Lulla A, Stogniew M, Schalop L, Benes C, Kaufman HL, Pottorf RS, Nallaganchu BR, Olson GL, Al-Mulla F, Duvic M, Wu GS, Dicker DT, Talekar MK, Lim B, Elemento O, Oster W, Bertino J, Flaherty K, Wang ML, Borthakur G, Andreeff M, Stein M, El-Deiry WS. Discovery and clinical introduction of first-in-class imipridone ONC201. Oncotarget. 2016 Nov 8;7(45):74380-74392. doi: 10.18632/oncotarget.11814.

  PMID: 27602582 BACKGROUND

• Hayes-Jordan AA, Ma X, Menegaz BA, Lamhamedi-Cherradi SE, Kingsley CV, Benson JA, Camacho PE, Ludwig JA, Lockworth CR, Garcia GE, Craig SL. Efficacy of ONC201 in Desmoplastic Small Round Cell Tumor. Neoplasia. 2018 May;20(5):524-532. doi: 10.1016/j.neo.2018.02.006. Epub 2018 Apr 5.

  PMID: 29626752 BACKGROUND

• Prabhu VV, Lulla AR, Madhukar NS, Ralff MD, Zhao D, Kline CLB, Van den Heuvel APJ, Lev A, Garnett MJ, McDermott U, Benes CH, Batchelor TT, Chi AS, Elemento O, Allen JE, El-Deiry WS. Cancer stem cell-related gene expression as a potential biomarker of response for first-in-class imipridone ONC201 in solid tumors. PLoS One. 2017 Aug 2;12(8):e0180541. doi: 10.1371/journal.pone.0180541. eCollection 2017.

  PMID: 28767654 BACKGROUND

• Anderson PM, Hanna R. Defining Moments: Making Time for Virtual Visits and Catalyzing Better Cancer Care. Health Commun. 2020 May;35(6):787-791. doi: 10.1080/10410236.2019.1587695. Epub 2019 Mar 24.

  PMID: 30907145 BACKGROUND

• Anderson PM, Trucco MM, Tarapore RS, Zahler S, Thomas S, Gortz J, Mian O, Stoignew M, Prabhu V, Morrow S, Allen JE. Phase II Study of ONC201 in Neuroendocrine Tumors including Pheochromocytoma-Paraganglioma and Desmoplastic Small Round Cell Tumor. Clin Cancer Res. 2022 May 2;28(9):1773-1782. doi: 10.1158/1078-0432.CCR-21-4030.

  PMID: 35022321 RESULT

MeSH Terms

Conditions

Neuroendocrine Tumors

Interventions

TIC10 compound

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue

Results Point of Contact

• Title: Dr. Peter Anderson
• Organization: Cleveland Clinic Pediatric and Taussig Cancer Institute, Case Comprehensive Cancer Center

andersp@ccf.org

216-308-2706

Study Officials

• Peter M Anderson, MD, PhD

  Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Site Principal Investigator

Study Record Dates

• First Submitted: January 25, 2017
• First Posted: January 27, 2017
• Study Start: August 2, 2017
• Primary Completion: May 19, 2023
• Study Completion: May 19, 2023
• Last Updated: November 26, 2024
• Results First Posted: November 26, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)