Phase 2 Study of ONC201 in Neuroendocrine Tumors

NCT ID: NCT03034200

Last Updated: 2024-11-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-08-02
• Study Completion Date: 2023-05-19

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.

Detailed Description

Primary Objective To demonstrate objective responses using MRI or CT, and/or PET-CT imaging. The same CT or MRI imaging to assess disease burden at study entry will be compared at week 6 and 3 months. Patients without progression at 3 months will continue treatment and have imaging at 6, 9 and 12 months after study entry. Metabolic response and/or biomarkers will be compared with study entry PET-CT and scans at 6 weeks, 3 months and 12 months.

Secondary Objectives Progression - free Survival: This will be calculated according to Response Evaluation Criteria In Solid Tumors (RECIST) or development of new disease

Overall survival: Overall survival will be determined by email or telephone contact.

Study Design: Phase 2 open-label fixed dose study Metastatic neuroendocrine tumors including PC-PG are rare diseases.

The current recommended phase II dose of 625 mg orally on 2 consecutive days every week will be used. The same imaging at study entry will be used at subsequent time points (CT or MRI for week 6 and 3, 6, 9, and 12 months) Imaging modality choice will be influenced by the quality of prior scans of the subject and will be ordered so clinical comparison is possible.

Because of travel and lodging considerations associated with the COVID-19 pandemic, some information by the study team/PI may be obtained using virtual visits and 2nd read of scans sent to Cleveland Clinic

Conditions

Recurrent Neuroendocrine Tumor; Metastatic Neuroendocrine Tumor

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A: Metastatic PC-PG

625mg ONC201 will be given once weekly

Group Type: EXPERIMENTAL

ONC201

Intervention Type: DRUG

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

Arm B: Other NETs

625mg ONC201 will be given once weekly

Group Type: EXPERIMENTAL

ONC201

Intervention Type: DRUG

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

Arm C: PC-PG + other NETs

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

Group Type: EXPERIMENTAL

ONC201

Intervention Type: DRUG

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

Interventions

ONC201

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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%

• Minimum Eligible Age: 14 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Peter Anderson

OTHER

Sponsor Role: lead

Responsible Party

Peter Anderson

Site Principal Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Peter M Anderson, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Locations

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

Cleveland, Ohio, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 23390247 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 25927855 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 25681273 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 27602582 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 29626752 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 28767654 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 30907145 (View on PubMed)

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.

Reference Type: RESULT

PMID: 35022321 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

CASE2716

Identifier Type: -

Identifier Source: org_study_id