SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT01631279

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

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.

NCT01631279 Unspecified Adult Solid Tumor, Protocol Specific

1 Interventions

Name: PR610

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

Type: Drug

PR610


Primary Outcomes

Description: 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).

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

Time: 3 weeks (1 cycle)

Description: 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

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

Time: 3 weeks (1 Cycle)

Secondary Outcomes

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

Measure: Evaluate the safety profile of PR610: Adverse Events

Time: 30 days following the last administration of study treatment

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

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

Description: 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

Measure: 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

Time: 30 days following the last administration of study treatment

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

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

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

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

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

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

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

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

Purpose: Treatment

Single Group Assignment


There is one SNP

SNPs


1 T790M

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. --- T790M ---

- 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 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 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. --- T790M ---



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