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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01631279




Registration number
NCT01631279
Ethics application status
Date submitted
7/06/2012
Date registered
27/06/2012
Date last updated
13/06/2014

Titles & IDs
Public title
A Dose Escalation Trial of PR610 Treating Patients With Solid Tumors
Scientific title
A Phase I/II, Multi-Center, Open-Label, Dose Escalation Trial of the Safety and Pharmacokinetics of Intravenous PR610 Given Weekly in Subjects With Solid Tumors
Secondary ID [1] 0 0
PR610-1001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Unspecified Adult Solid Tumor, Protocol Specific 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - PR610

Experimental: PR610 -


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

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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).
Timepoint [1] 0 0
3 weeks (1 cycle)
Primary outcome [2] 0 0
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
Timepoint [2] 0 0
3 weeks (1 Cycle)
Secondary outcome [1] 0 0
Evaluate the safety profile of PR610: Adverse Events - The number of adverse events experienced by participants will be measured.
Timepoint [1] 0 0
30 days following the last administration of study treatment
Secondary outcome [2] 0 0
Peak Plasma Concentration (Cmax) of PR610 and PR610E for Both a 1-hour and a 24-hour Weekly Infusion
Timepoint [2] 0 0
pre, 30 minutes into infusion, end of infusion, 1, 2, 4, 24, 48, and 72 hours post-infusion on Cycles 1 and 2
Secondary outcome [3] 0 0
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 - Efficacy will be determined for each subject that received at least one dose of PR610 and had at least one post-baseline disease assessment. The following four outcomes will be tabulated:
Tumor response Time to response Duration of response Progression-free survival
Timepoint [3] 0 0
30 days following the last administration of study treatment
Secondary outcome [4] 0 0
Time of Peak Plasma Concentration (tmax) of PR610 and PR610E for Both a 1-hour and a 24-hour Weekly Infusion
Timepoint [4] 0 0
pre, 30 minutes into infusion, end of infusion, 1, 2, 4, 24, 48, and 72 hours post-infusion on Cycles 1 and 2
Secondary outcome [5] 0 0
Half life (t1/2) of PR610 and PR610E for Both a 1-hour and a 24-hour Weekly Infusion
Timepoint [5] 0 0
pre, 30 minutes into infusion, end of infusion, 1, 2, 4, 24, 48, and 72 hours post-infusion on Cycles 1 and 2
Secondary outcome [6] 0 0
Area Under the Curve (AUC) of PR610 and PR610E for Both a 1-hour and a 24-hour Weekly Infusion
Timepoint [6] 0 0
pre, 30 minutes into infusion, end of infusion, 1, 2, 4, 24, 48, and 72 hours post-infusion on Cycles 1 and 2
Secondary outcome [7] 0 0
Clearance (CL) of PR610 and PR610E for Both a 1-hour and a 24-hour Weekly Infusion
Timepoint [7] 0 0
pre, 30 minutes into infusion, end of infusion, 1, 2, 4, 24, 48, and 72 hours post-infusion on Cycles 1 and 2

Eligibility
Key inclusion criteria
- Signed informed consent

- Age 18 years or more

- Histologically-confirmed, progressive cancer with the following diagnosis:

1. Phase I: locally advanced or metastatic solid tumor that may respond to an EGFR
inhibitor;

2. 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

1. except for grade 1 fatigue, grade 1 peripheral sensory neuropathy and grade 1 or
2 alopecia during the phase I portion of the study

2. 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

- Adequate hematological and biological function

- Willingness to participate in PK sampling during cycles 1 and 2

- Willingness to provide permission to access archived tumor samples for evaluation of
EGFR mutation status

- Willingness to provide samples for storage of normal tissue containing wild-type DNA

Additional Inclusion Criteria during Expansion Phase

- At least one target lesion as defined by RECIST 1.1 that allows for evaluation of
tumor response
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- 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

Additional Exclusion Criteria during Expansion Phase

- Any other malignancy likely to effect the assessment of toxicity or efficacy of PR610

Study design
Purpose of the study
Treatment
Allocation to intervention
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1/Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Illinois
Country [4] 0 0
United States of America
State/province [4] 0 0
Texas
Country [5] 0 0
New Zealand
State/province [5] 0 0
Auckland
Country [6] 0 0
New Zealand
State/province [6] 0 0
Waikato

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Proacta, Incorporated
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT01631279
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Proacta Inc.
Address 0 0
Proacta, Incorporated
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No data has been provided for results reporting
Summary results
Not applicable