A Dose-Escalation Study of Onc201 Administered Every One or Three Weeks in Advanced Solid Tumors and Multiple Myeloma

NCT02609230 | Completed Phase 1 DMC

• 2 other identifiers: PH-07715-1009
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

This study will determine the maximum tolerated dose (MTD) and/or the recommended phase II dose (RP2D) of single agent ONC201 in patients with advanced solid tumors or multiple myeloma.

Conditions

Advanced Solid Tumors; Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Determine the maximum tolerated dose of ONC201

  At day 21 of Cycle 1 of therapy

Secondary Outcomes (1)

• Peak Plasma Concentration of ONC201

  0, 0.5, 2, 4, 6, 24, 48, 72, 168 hours post dose

Study Arms (2)

A

EXPERIMENTAL

For the first arm (A), dose escalation will use the following single patient dose-escalation cohorts based on 'Design 4' proposed by Simon and colleagues: 125, 250, and 500 mg. every 3 weeks.

Drug: ONC-201

B

EXPERIMENTAL

Following completion of Arm A dose escalation, subsequent cohorts will be tested in a minimum of 3 patients, the Arm B dose cohort will consist of dose levels administered every week (planned dosing of 250, 375, 500 and 625 mg).

Drug: ONC-201

Interventions

ONC-201 DRUG

A; B

Eligibility Criteria

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

You may qualify if:

• Solid tumor specific:
• Patients must have a histologically/cytologically confirmed primary solid tumor
• Radiographic or clinical evidence of advanced/metastatic malignant disease that is resistant to standard therapy or for which no standard therapy is available. Lesions may be measurable or non-measurable
• Multiple myeloma specific:
• Confirmed evidence of disease progression from immediately prior MM therapy or refractory to the immediately prior treatment
• 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).
• Subjects with free light chain only disease are excluded
• All previous therapies for cancer, including radiotherapy, major surgery and investigational therapies discontinued for ≥ 14 days (≥ 28 days for mitomycin C or nitrosoureas ) before Cycle 1 Day 1 (C1D1), and 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
• Age ≥ 18 years
• ECOG performance status ≤ 1
• Adequate organ and marrow function as defined below:
• Absolute neutrophil count ≥1,000/mm3 without growth factor use ≤ 7 days prior to C1D1
• Platelets ≥75,000/mm3 without platelet transfusion ≤ 7 days prior to C1D1
• Hemoglobin \>8.0 mg/dL without red blood cell transfusion ≤ 7 days prior to C1D1
• Total serum bilirubin \<1.5 X upper limit of normal (ULN)

You may not qualify if:

• Patients with symptomatic brain metastases are excluded. Patients with asymptomatic and treated CNS metastases may participate in this trial. The patient must have completed any prior treatment for CNS metastases \> 28 days prior to study entry including radiotherapy or surgery. Steroids for the treatment of brain metastasis are not permitted.
• 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 is allowed.
• Pregnancy or breast feeding
• Current active treatment in another clinical study
• Active bacterial, fungal or viral infection including hepatitis B (HBV), hepatitis C (HCV), requiring treatment with IV antibiotic, IV anti-fungal, or anti-viral.
• Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness.
• Multiple myeloma specific:
• Active or prior plasma cell leukemia (defined as either 20% of peripheral WBC comprised of plasma/CD138+ cells or an absolute count of 2 x 10\^9/L)
• Solitary bone or solitary extramedullary plasmacytoma as the only evidence of plasma cell dyscrasia.
• Subjects with serum calcium (corrected for albumin) ≥ 12 mg/dL
• 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.
• Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, or in the judgment of the investigator would make the patient inappropriate for entry into the study.

Sponsors & Collaborators

• Fox Chase Cancer Center: lead

Study Sites (1)

Fox Chase Cancer Center - Philadelphia

Philadelphia, Pennsylvania, 19111-2497, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

TIC10 compound

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

Study Officials

• Anthony Olszanski, MD

  Fox Chase Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: November 10, 2015
• First Posted: November 20, 2015
• Study Start: November 5, 2015
• Primary Completion: March 1, 2020
• Study Completion: March 26, 2020
• Last Updated: June 4, 2021

Record last verified: 2021-06

Locations

US (1)