A Phase 1b Study of PEGylated Recombinant Human Hyaluronidase (PEGPH20) Combined With Docetaxel in Subjects With Recurrent Previously Treated Locally Advanced or Metastatic NSCLC
This trial is active, not recruiting.
|Condition||non-small cell lung cancer|
|Start date||November 2014|
|End date||December 2016|
|Trial size||80 participants|
|Trial identifier||NCT02346370, HALO-107-201|
A Phase 1b study for subjects with Stage IIIB/IV NSCLC to participate in 1 of 2 portions of this study. The first portion is Dose Escalation in which subjects are tested with PEGPH20 at various doses (1.6, 3.0, 2.2 and 2.8 mcg/kg) in addition to dosing with the standard dose of docetaxel of 75 mg/m2 (PDoc) once every 21-day cycle. Based on observations on the safety and tolerability of study treatment from dose escalation cohorts dosed to date (1.6 and 3.0 mcg/kg of PEGPH20), two additional dose levels will be tested, 2.2 and 2.8 mcg/kg. Up to 30 additional subjects may be enrolled to test these dose levels. The second portion of Phase 1b is Cohort Expansion in which the recommended Phase 2 dose (RP2D) of PDoc identified in dose escalation is administered every 21 days to approximately 50 subjects with high hyaluronan (HA-high) prospectively measured in their tumor tissue.
|United States||No locations recruiting|
|Other countries||No locations recruiting|
|Encinitas, CA||California Cancer Associates for Research and Excellence (cCare)||no longer recruiting|
|Fresno, CA||California Cancer Associates for Research and Excellence (cCare)||no longer recruiting|
|San Diego, CA||Moores UCSD Cancer Center, Clinical Trials Office||no longer recruiting|
|Lebanon, NH||Dartmouth-Hitchcock Medical Center||no longer recruiting|
|Rochester, NY||University of Rochester||no longer recruiting|
|Charlotte, NC||Levine Cancer Institute||no longer recruiting|
|Canton, OH||Gabrail Cancer Center Research||no longer recruiting|
|Cleveland, OH||University Hospitals of Cleveland||no longer recruiting|
|Hershey, PA||Penn State Milton S. Hershey Medical Center||no longer recruiting|
|Endpoint classification||safety/efficacy study|
|Intervention model||single group assignment|
PEGPH20 (RP2D) intravenously once every 3 weeks + Docetaxel 75 mg/m2 intravenously once every 3 weeks
Incidence of Dose Limiting Toxicities and Maximum Tolerated Dose/Recommended Phase 2 Dose in Dose Escalation
time frame: 12 months
Incidence of Adverse Events and changes in clinical safety laboratory values and cardiovascular parameters in Dose Escalation and Cohort Expansion
time frame: 12 months
Noncompartmental and compartmental PK Parameters for PEGPH20 and docetaxel: Maximum observed concentration, Cmax, Cmin, tmax, terminal 1/2 life, AUC, Volume of distribution and Clearance.
time frame: 12 months
Objective Response Rate (ORR), Disease Control Rate (DCR), Duration of Response (DOR), and Progression Free Survival (PFS) in the Dose Escalation and Cohort Expansion portions.
time frame: 12 Months
Male or female participants at least 18 years old.
- Signed, approved Informed Consent.
- Histologically confirmed and documented previously treated Stage IIIB/IV NSCLC, having failed 1 previous platinum chemo regimen for locally advanced or metastatic disease.
- Cohort Expansion: Available archival tumor tissue block or 5-10 unstained, consecutive core biopsy slides from one archival tumor block that meet specific tissue requirements.
- Cohort Expansion: Subjects must be determined to be HA-high based on tumor biopsy that meets the requirements noted in the previous inclusion criterion.
- Cohort Expansion: One or more tumors measurable on CT/MRI scan per RECIST v 1.1 (Eisenhauer 2009; Appendix C).
- Subjects may have failed a programmed cell death protein 1 (PD-1) or programmed death-ligand 1 (PD-L1) therapy for advanced disease.
- Subjects that are known to be epidermal growth factor (EGFR)-activating mutation positive must have received an EGFR inhibitor.
- Subjects known to be anaplastic lymphoma kinase (ALK)-fusion/rearrangement mutation positive must have received an ALK inhibitor.
- Most prior therapies and prior targeted therapy are allowed and these specific therapies are detailed in the protocol.
- Life expectancy - =/> 3 months, Eastern Cooperative Oncology Group status = 0 or 1.
- Negative urine or serum pregnancy test within 7 days before Day 1 (first dose of study medication) if female subject is of childbearing potential (WOCBP).
- Men and women agreement to use effective contraceptive method. For WOCBP and for men, agreement to use an effective contraceptive method from the time of screening throughout the study until 1 month for WOCBP or 6 months for men after administration of the last dose of any study medication.
- Specific ranges/levels of Screening labs that are acceptable per protocol.
- Age >/= 18 years.
- Previous treatment with docetaxel.
- Failed more than 3 treatment regimens for locally advanced or metastatic NSCLC.
- New York Heart Assoc Class III or IV cardiac disease, myocardial infarction within the past 12 months before screening, or pre-existing atrial fibrillation.
- History of cerebrovascular accident or transient ischemic attack.
- Pre-existing carotid artery disease.
- Previous history of pulmonary embolism or pulmonary embolism found on screening exam.
- No ongoing requirement for corticosteroids
- Active, uncontrolled bacterial, viral, or fungal infection requiring systemic therapy at time of screening.
- Known infection with HIV and active infection with hepatitis B or C.
- Known allergy to hyaluronidase or any constituents of docetaxel formulation.
- Current use (within 10 days of day 1) of megestrol acetate.
- Chronic concomitant use of strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, and voriconazole).
- Women currently pregnant or breast feeding.
- Intolerance to dexamethasone, as determined by Investigator.
- History of another primary cancer within the last 3 years that required treatment, with the exception of non-melanoma skin cancer, early stage prostate cancer, or curatively treated cervical carcinoma in situ.
- Any other disease, metabolic dysfunction, physical exam finding, or clinical lab finding that leads to reasonable suspicion of disease that contraindicates the use of an investigational drug that might affect interpretation of results or render subject at high risk for treatment complications.
- In opinion of Investigator, make subject unsuitable for study.
- Hypersensitivity to the active substance or ingredients of PEGPH20 and docetaxel.
- Subject's inability to comply with study and follow-up procedures, as judged by the Investigator.
|Official title||PRIMAL STUDY: A Phase 1b, Open-label, Multicenter, Multinational Study of PEGylated Recombinant Human Hyaluronidase (PEGPH20) Combined With Docetaxel (PDoc) in Subjects With Recurrent Previously Treated Locally Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC)|
|Description||This is a Phase 1b study for subjects with Stage IIIB/IV NSCLC to participate in 1 of 2 portions of this study. The first portion of the Phase 1b is Dose Escalation which will enroll up to 30 subjects testing various dose levels of PEGPH20 (1.6, 2.2, 2.8 and 3.0 mcg/kg) plus docetaxel 75mg/m2 once every 3 weeks until the maximum tolerated dose or MTD is found. Based on observations on the safety and tolerability of study treatment from dose escalation cohorts dosed to date (1.6 and 3.0 mcg/kg of PEGPH20), two additional dose levels, 2.2 and 2.8 mcg/kg will be tested. The 2nd portion of Phase 1b is Cohort Expansion. This portion will enroll approximately 50 subjects at the MTD/RP2D of PDoc given every 21-day cycle. These subjects will be pre-selected with high levels of HA measured in their tumor tissue sample prior to enrollment. After the Phase 1b is completed, all data will be analyzed and the safest, best tolerated and most efficacious dose of PDoc will be used in a planned separate Phase 2 study.|
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