Phase 1 Study of Oprozomib Administered Orally in Patients With Advanced Refractory or Recurrent Solid Tumors

NCT01129349 | Completed Phase 1

• 1 other identifier: 2009-003
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 3

Brief Summary

To evaluate the safety and tolerability of Oprozomib in patients with advanced refractory or recurrent solid tumors including determination of its Dose Limiting Toxicity (DLT) and Maximum Tolerated Dose (MTD) To determine the pharmacokinetics (PK) of Oprozomib To explore the anti-tumor activity of Oprozomib in this patient population including the overall response rate (ORR), the duration of responses (DOR), the progression-free survival (PFS) and time to progression (TTP) To define the pharmacodynamics (PDn) of Oprozomib.

Conditions

Solid Tumors

Keywords

Solid Tumors

Outcome Measures

Primary Outcomes (1)

• Dose Limiting Toxicity (DLT) and Maximum Tolerated Dose (MTD)

  * To evaluate the safety and tolerability of Oprozomib in patients with advanced refractory or recurrent solid tumors including determination of its Dose Limiting Toxicity (DLT) and Maximum Tolerated Dose (MTD) * To determine the pharmacokinetics (PK) of Oprozomib

  31 months

Secondary Outcomes (1)

• Overall response rate (ORR), duration of responses (DOR), progression-free survival (PFS), and time to progression (TTP)

  31 months

Study Arms (1)

Oprozomib

EXPERIMENTAL

Phase I, Dose Escalation, Single Arm, Open Label

Drug: Oprozomib

Interventions

Oprozomib DRUG

Oral administration of Oprozomib on Days 1-5 of a 14 day cycle

Oprozomib

Eligibility Criteria

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

You may qualify if:

• Disease Related
• Histologically confirmed advanced solid tumor that is refractory or recurrent after standard treatments.
• At least one site of radiographically measurable disease of ≥ 2 cm in the largest dimension by traditional computed tomography (CT) scanning technique or ≥ 1 cm in the largest dimension by spiral CT scanning (per RECIST criteria); or if, in the Principal Investigator's opinion, evaluable disease can be reliably and consistently followed, the patient may be eligible upon approval by the Onyx Therapeutics, Inc., Medical Monitor.
• Demographic
• Males and females ≥ 18 years of age
• Life expectancy of more than three months
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
• Laboratory
• Adequate hepatic function, with bilirubin ≤ 1.5 times the upper limit of normal (ULN), and alanine aminotransferase (ALT) ≤ 3 times ULN or ≤ 5 times ULN in the presence of hepatic tumor involvement
• Absolute neutrophil count (ANC) ≥ 1500/mm3, hemoglobin ≥ 8 g/dL, and platelet count ≥ 100,000/ mm3
• Screening platelet count must be independent of platelet transfusions for at least one week
• Screening ANC must be independent of granulocyte- and granulocyte/macrophage colony stimulating factor (G-CSF and GM-CSF) support for at least one week and of pegylated G-CSF for at least two weeks
• Patients may receive red blood cell (RBC) transfusions or receive supportive care with erythropoietin or darbepoetin in accordance with institutional guidelines
• Calculated or measured creatinine clearance of ≥ 30 mL/min; calculation using a generally accepted formula such as that of Cockcroft and Gault: CrCl = \[(140 - Age) × Mass (kg) / (72 × Creatinine mg/dL)\], multiply by 0.85 if female
• Ethical / Other

You may not qualify if:

• Disease Related
• Chemotherapy with approved or investigational anticancer therapeutics, including steroid therapy, within four weeks prior to first dose of Oprozomib or six weeks for antibody therapy
• Radiation therapy or immunotherapy within three weeks prior to first dose; localized radiation therapy within one week prior to first dose Patients with brain metastases (patients with prior brain metastases are permitted, but must have completed treatment and have no evidence of active CNS disease for at least three months prior to first dose)
• Prior treatment with a proteasome inhibitor
• Concurrent Conditions
• Major surgery within three weeks prior to first dose
• Congestive heart failure (New York Heart Association Class III to IV), symptomatic ischemia, or conduction abnormalities. Conduction system abnormalities not clinically warranting intervention are allowed.
• Myocardial infarction within three months prior to first dose
• Active infection requiring systemic antibiotics, antivirals, or antifungals within two weeks prior to first dose
• HIV infection (HIV seropositive)
• Active hepatitis A, B, or C infection
• Peripheral neuropathy of Grade ≥ 3 or Grade 2 with pain at the time of the first dose
• Patients with pleural effusions requiring repeat thoracentesis or ascites requiring repeat paracentesis
• Prior Oprozomib therapy
• Hypersensitivity to Oprozomib or any of its components

Sponsors & Collaborators

• Amgen: lead

Study Sites (3)

Oncology Research Associates

Scottsdale, Arizona, 85258, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, United States

Location

South Texas Accelerated Research Therapeutics

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Interventions

ONX 0912

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: May 21, 2010
• First Posted: May 24, 2010
• Study Start: April 1, 2010
• Primary Completion: November 1, 2012
• Study Completion: March 1, 2013
• Last Updated: May 2, 2017

Record last verified: 2017-04

Locations

US (3)