A Dose Escalation Trial of PR610 Treating Patients With Solid Tumors

NCT01631279 | Terminated Phase 1

• 1 other identifier: PR610-1001
• Study Type: interventional
• Target: 33
• Locations: 2 countries
• Sites: 6

Brief Summary

The purpose of this study is to determine the Maximum Tolerated Dose and the Dose-Limiting Toxicity of the drug to further evaluate safety and antitumor activity.

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Keywords

NSCLC; non-small cell lung cancer; non-squamous, non-small cell lung cancer; solid tumors; lung cancer

Outcome Measures

Primary Outcomes (2)

• Determine the Maximum Tolerated Dose (MTD) of PR610 for Both a 1-hour and a 24-hour Weekly IV Infusion

  The first cohort of three subjects will receive PR610 at Dose Level 1. Subsequent cohorts will receive PR610 at a dose levels determined as per dose escalation criteria. The MTD will be defined as the dose level at which one (1) or fewer subject in six exhibit DLT with the next highest dose level demonstrating two (2) or more of six (6) subjects with DLT (or for which more than ≥33% of subjects exhibit DLT if the cohort size exceeds 6 subjects).

  3 weeks (1 cycle)

• Determine the Dose-Limiting Toxicity (DLT) of PR610 for Both a 1-hour and a 24-hour Weekly IV Infusion

  DLT is defined as the following: * Occurs during the first cycle of PR610 * Is considered PR610-related, as defined by "Definitely-related", "Probably-related" or "Possibly-related" * Is clinically significant, as determined by the Principal Investigator In addition, DLT will meet at least one of the criteria listed below using grading criteria from the CTCAEv4. * Grade 4 hematologic toxicity * Any drug-related toxicity that prevents administration of 100% of all doses of PR610 planned for Cycle 1 * Grade 3 or higher non-hematologic toxicity

  3 weeks (1 Cycle)

Secondary Outcomes (7)

• Evaluate the safety profile of PR610: Adverse Events

  30 days following the last administration of study treatment

• Peak Plasma Concentration (Cmax) of PR610 and PR610E for Both a 1-hour and a 24-hour Weekly Infusion

  pre, 30 minutes into infusion, end of infusion, 1, 2, 4, 24, 48, and 72 hours post-infusion on Cycles 1 and 2

• Evaluate the activity of PR610 in a general phase I population and in a subset of subjects with NSCLC genetically resistant to reversible EGFR inhibitors

  30 days following the last administration of study treatment

• Time of Peak Plasma Concentration (tmax) of PR610 and PR610E for Both a 1-hour and a 24-hour Weekly Infusion

  pre, 30 minutes into infusion, end of infusion, 1, 2, 4, 24, 48, and 72 hours post-infusion on Cycles 1 and 2

• Half life (t1/2) of PR610 and PR610E for Both a 1-hour and a 24-hour Weekly Infusion

  pre, 30 minutes into infusion, end of infusion, 1, 2, 4, 24, 48, and 72 hours post-infusion on Cycles 1 and 2

Study Arms (1)

PR610

EXPERIMENTAL

Drug: PR610

Interventions

PR610 DRUG

Dose escalation of PR610 to determine maximum tolerated dose for weekly administration

PR610

Eligibility Criteria

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

You may qualify if:

• Signed informed consent
• Age 18 years or more
• Histologically-confirmed, progressive cancer with the following diagnosis:
• Phase I: locally advanced or metastatic solid tumor that may respond to an EGFR inhibitor;
• Phase II: Stage IIIB or IV, non-squamous, non-small cell lung cancer (NSCLC) with known sensitizing mutations in EGFR, and the T790M resistance mutation
• Failed, refused, or not eligible for standard of care therapy
• ECOG performance status of 0, 1, or 2
• Life expectancy of at least 12 weeks
• At least 4 weeks from prior anticancer therapy including chemotherapy, hormonal, investigational, and/or biological therapies and irradiation. Ongoing hormonal therapy administered for control of prostate cancer which may be continued through the study. In addition, in the phase II portion of the study, prior reversible EGFR tyrosine kinase inhibitor therapy, such as erlotinib or gefitinib, may be continued up to 48 hours prior to start of PR610 to prevent significant disease flare.
• Recovered from prior treatment related toxicity
• except for grade 1 fatigue, grade 1 peripheral sensory neuropathy and grade 1 or 2 alopecia during the phase I portion of the study
• except for grade 1 toxicity, and grade 2 peripheral neuropathy during the phase II portion of the study
• At least four (4) weeks from prior major surgery
• Women of child-bearing potential must be willing to use an acceptable contraceptive method and must have a negative urine or serum pregnancy test within 2 weeks prior to beginning treatment on this trial
• Sexually active men must be willing to use an acceptable contraceptive method

You may not qualify if:

• Pregnant or nursing women
• Any uncontrolled medical illness including, but not limited to, significant gastrointestinal disorders, cardiovascular disease, or interstitial lung disease
• History of clinically significant cardiovascular abnormalities, eg., uncontrolled hypertension, CHF (NYHA classification ≥2), unstable angina, poorly controlled arrhythmias, myocardial infarction within 6 months of study entry, implantable pacemaker or implantable cardioverter defibrillator
• Clinically significant abnormal 12-lead ECG with QTcF \>450 msec
• Use of any medications known to produce QT prolongation
• Family history of Long QT Syndrome
• Prior treatment with anthracyclines with a cumulative dose of doxorubicin (or equivalent) ≥400 mg/m2
• Cardiac left ventricular function with resting ejection fraction of less than 50%
• Symptomatic CNS lesions or known CNS lesions that require therapy
• Prior history of an allergic reaction to a tyrosine kinase inhibitor
• Any other malignancy likely to effect the assessment of toxicity or efficacy of PR610

Sponsors & Collaborators

• Proacta, Incorporated: lead

Study Sites (6)

Scottsdale Healthcare

Scottsdale, Arizona, 85258, United States

Location

University of California-Davis Comprehensive Cancer Ctr

Sacramento, California, 95817, United States

Location

Robert H. Lurie Comprehensive Cancer Research Center

Chicago, Illinois, 60611, United States

Location

South Texas Accelerated Research Therapeutics

San Antonio, Texas, 78229, United States

Location

Auckland City Hospital

Auckland, New Zealand

Location

Waikato Hospital

Waikato, New Zealand

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Proacta Inc.

  Proacta, Incorporated

  STUDY CHAIR

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: June 7, 2012
• First Posted: June 29, 2012
• Study Start: August 1, 2012
• Primary Completion: March 1, 2015
• Study Completion: August 1, 2015
• Last Updated: June 16, 2014

Record last verified: 2014-06

Locations

US (4); NZ (2)