Oral ONC201 in Relapsed/Refractory Multiple Myeloma

NCT02863991 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: ONC007R01FD005402
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 2

Brief Summary

This was a Phase 1/2 open-label study of ONC201 administered orally once every week in combination with dexamethasone in adults with relapsed/refractory multiple myeloma. The primary objective of this study was to evaluate the antitumor efficacy of ONC201. Note: This study was completed by predecessor company, Oncoceutics, Inc.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Response of Participants at Last On-study Visit (End of Treatment/Follow-up)

  Assessments of response were made using the International Myeloma Working Group (IMWG) response criteria and were assessed by magnetic resonance imaging (MRI), computed tomography (CT), or positron emission tomography (PET)/CT scans (when applicable). Per IMWG response criteria, objective response could be defined as follows: complete response (CR), disappearance of any soft tissue plasmacytomas; partial response (PR), a \>50% reduction in size of soft tissue plasmacytomas; progressive disease (PD), definite development of new or a definite increase of size of existing soft tissue plasmacytomas; and stable disease (SD), not meeting criteria for CR, PR, or PD.

  The response assessment data reported was conducted at the last on-study visit (end of treatment/follow-up), up to a maximum of 7 months following treatment initiation.

Study Arms (2)

375 mg ONC201

EXPERIMENTAL

Patients received 375 mg ONC201 once every week in combination with dexamethasone.

Drug: ONC201; Drug: Dexamethasone

625 mg ONC201

EXPERIMENTAL

Patients received 625 mg ONC201 once every week in combination with dexamethasone.

Drug: ONC201; Drug: Dexamethasone

Interventions

ONC201 DRUG

375 mg or 625 mg ONC201

375 mg ONC201; 625 mg ONC201

Dexamethasone DRUG

20 mg dexamethasone

375 mg ONC201; 625 mg ONC201

Eligibility Criteria

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

You may qualify if:

• A patient had to meet all of the following criteria to be eligible to participate in the study:
• Must have been refractory to, or not a candidate for, established therapy known to provide clinical benefit for their malignancy.
• Had measurable disease M protein component in serum (at least 0.5 g/dL) and/or urine (if present) (≥0.2 g excreted in a 24 hour collection sample), or serum free light chain level ≥10 mg/dL, provided the serum free light chain ratio was abnormal.
• Was able to swallow and retain oral medication.
• Had all previous therapies for cancer, including radiotherapy, major surgery and investigational therapies discontinued for ≥14 days (≥28 days for mitomycin C or nitrosoureas) before study entry, and had all acute effects of any prior therapy resolved to baseline severity or Grade ≤1 Common Terminology Criteria for Adverse Events (CTCAE v4.03), except alopecia or parameters defined in this eligibility list.
• Were aged ≥18 years.
• Had an Eastern Cooperative Oncology Group (ECOG) performance status of ≤1.
• Had adequate organ and marrow function as defined below:
• Absolute neutrophil count: ≥1,000/mm3 without growth factor use ≤7 days prior to treatment (cycle 1 day 1, C1D1)
• Platelets: ≥75,000/mm3 without platelet transfusion ≤3 days prior to C1D1
• Hemoglobin: 8.0 mg/dL without red blood cell transfusion ≤3 days prior to C1D1
• Total serum bilirubin: ≤1.5 X upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (SGOT)/alanine aminotransferase (ALT) (SGPT): ≤2 X ULN; ≤ 5 X ULN if liver dysfunction was felt to be secondary to tumor burden
• Serum creatinine: ≤1.5 X ULN (OR creatinine clearance ≥30 mL/min/1.73 m2)
• Serum or urine pregnancy test (for females of childbearing potential) negative ≤7days of starting treatment

You may not qualify if:

• A potential patient who met any of the following criteria was ineligible to participate in the study:
• Had active inflammatory gastrointestinal disease, chronic diarrhea (unless related to underlying malignancy or prior related treatment) or history of abdominal fistula, gastrointestinal perforation, peptic ulcer disease, or intra-abdominal abscess within 6 months prior to study enrollment. Gastroesophageal reflux disease under treatment with proton pump inhibitors was allowed.
• Was pregnant or breast feeding.
• Was undergoing current active treatment in another clinical study.
• Had active bacterial, fungal or viral infection including hepatitis B (HBV), hepatitis C (HCV)
• Had known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness that was not well controlled.
• Had active or prior plasma cell leukemia (defined as either 20% of peripheral white blood cell count \[WBC\] comprised of plasma/CD138+ cells or an absolute count of 2x10\^9/L).
• Had solitary bone or solitary extramedullary plasmacytoma as the only evidence of plasma cell dyscrasia.
• Had serum calcium (corrected for albumin) ≥12 mg/dL
• Had any of the following in the previous 6 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack or symptomatic pulmonary embolism.
• Had other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may have increased the risk associated with study participation or study drug administration, or may have interfered with the interpretation of study results, or in the judgment of the investigator would have made the patient inappropriate for entry into the study.

Sponsors & Collaborators

• Jazz Pharmaceuticals: lead
• Oncoceutics, Inc.: collaborator

Study Sites (2)

The Mount Sinai Medical Center

New York, New York, 10029-6574, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

TIC10 compound; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Limitations and Caveats

Note: This study was terminated due to a change in corporate priorities. The decision to terminate the study was not based on any safety concerns.

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Chimerix, Inc.

clinicaltrials@chimerix.com

919-806-1074

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 4, 2016
• First Posted: August 11, 2016
• Study Start: April 19, 2017
• Primary Completion: September 17, 2019
• Study Completion: December 16, 2019
• Last Updated: July 3, 2024
• Results First Posted: July 3, 2024

Record last verified: 2024-06

Locations

US (2)