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Unspecified Adult Solid Tumor, Protocol SpecificPhase 1/2NCT01631279

A Dose Escalation Trial of PR610 Treating Patients With Solid Tumors

A Phase 1/2 study testing PR610 in people with Unspecified Adult Solid Tumor, Protocol Specific, run by Proacta, Incorporated at 6 sites in 2 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
PR610
Could I receive a placebo?
No, everyone receives an active treatment
How many people
33 participants
Where
6 sitesin 2 countries
Study dates
Aug 2012to Aug 2015
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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
  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

6 sites in 2 countries.

6 sites in 2 countries

United States4 sites

  • Robert H. Lurie Comprehensive Cancer Research Center

    Chicago, Illinois, 60611

  • University of California-Davis Comprehensive Cancer Ctr

    Sacramento, California, 95817

  • South Texas Accelerated Research Therapeutics

    San Antonio, Texas, 78229

  • Scottsdale Healthcare

    Scottsdale, Arizona, 85258

Other trials in United States

New Zealand2 sites

  • Auckland City Hospital

    Auckland

  • Waikato Hospital

    Waikato

Other trials in New Zealand

About this study

Official 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

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.

Read the detailed description

Following informed consent, subjects undergo baseline evaluation and disease assessment. PR610 is administered intravenously weekly.

In the absence of progressive disease or unacceptable toxicity, subjects may continue to receive PR610. Intra-subject dose escalation (to no higher than the highest safe level) is allowed in subjects who are not experiencing dose limiting toxicity. Disease assessment will be repeated at week 6 and then every 8 weeks thereafter.

Pharmacokinetic (PK) assessment (PR610 and PR610E) will be performed for all subjects.

After determination of the MTD and the determination of the phase II dose, additional subjects with NSCLC that is genetically resistant to reversible EGFR inhibitors will be accrued into an expansion cohort.

Being tested
PR610
Keywords
NSCLC, non-small cell lung cancer, non-squamous, non-small cell lung cancer, solid tumors, lung cancer
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Lung Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PR610Drug

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

Study groups in NCT01631279
Study groupRoleWhat they receive
PR610ExperimentalNot described
Receives: Drug: PR610

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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).

    Measured: 3 weeks (1 cycle)

  2. 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

    Measured: 3 weeks (1 Cycle)

Secondary outcomes (7)

  1. Evaluate the safety profile of PR610: Adverse Events

    The number of adverse events experienced by participants will be measured.

    Measured: 30 days following the last administration of study treatment

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

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

  3. 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

    Measured: 30 days following the last administration of study treatment

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

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

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

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

  6. Area Under the Curve (AUC) of PR610 and PR610E for Both a 1-hour and a 24-hour Weekly Infusion

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

  7. Clearance (CL) of PR610 and PR610E for Both a 1-hour and a 24-hour Weekly Infusion

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Jun 2012 (estimated)
  2. Study startAug 2012
  3. Primary completionMar 2015 (estimated)
  4. Study completionAug 2015 (estimated)

Why it stopped: Study was prematurely discontinued due to unacceptable toxicity.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
33 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01631279
Sponsor's protocol ID
PR610-1001
Status last verified
Jun 2014
First submitted
7 Jun 2012
Last updated
16 Jun 2014
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing PR610 in people with Unspecified Adult Solid Tumor, Protocol Specific, run by Proacta, Incorporated at 6 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 16 Jun 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States, New Zealand. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Study was prematurely discontinued due to unacceptable toxicity.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Determine the Maximum Tolerated Dose (MTD) of PR610 for Both a 1-hour and a 24-hour Weekly IV Infusion (time frame: 3 weeks (1 cycle)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01631279.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jun 2014.

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