Clinical trial NCT02346370: A Phase 1b Study of PEGylated Recombinant Human Hyaluronidase (PEGPH20) Combined With Docetaxel in Subjects With Recurrent Previously Treated Locally Advanced or Metastatic NSCLC
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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Non-small Cell Lung Cancer
Keywords: Recurrent, previously treated, locally advanced or metastatic NSCLC (non small cell lung cancer)
Lead sponsor: Halozyme Therapeutics
Sponsor class: INDUSTRY
First posted: 2015-01-27
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Intervention model: SEQUENTIAL
Intervention model description: The study was planned to include a Dose Escalation portion utilizing a standard 3 + 3 dose escalation design. Participants were enrolled sequentially into their assigned dose cohort. The Treatment Period consisted of 21-day treatment cycles with administration of PEGPH20 on Day 1 (doses tested were 1.6, 3.0, and 2.2 ug/kg) and docetaxel (standard dosing 75 mg/m\^2 for all participants) on Day 2 of each cycle.
Primary purpose: TREATMENT

Brief summary: A Phase 1b study for participants with Stage IIIB/IV Non-Small Cell Lung Cancer (NSCLC) to participate in 1 of 2 portions of this study. The first portion is Dose Escalation in which participants are tested with PEGPH20 at various doses (1.6, 3.0, 2.2 and 2.8 micrograms/kilogram (ug/kg)) in addition to dosing with the standard dose of docetaxel (PDoc) of 75 milligrams/meter squared (mg/m\^2) 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 ug/kg of PEGPH20), two additional dose levels will be tested, 2.2 and 2.8 ug/kg. Up to 30 additional participants 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 participants with high hyaluronan (HA-high) prospectively measured in their tumor tissue.


Eligibility criteria: Inclusion Criteria:

* Signed, approved Informed Consent.
* Histologically confirmed and documented previously treated Stage IIIB/IV Non-Small Cell Lung Cancer (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: Participants must be determined to be hyaluronidase (HA)-high based on tumor biopsy that meets the requirements noted in the previous inclusion criterion.
* Cohort Expansion: One or more tumors measurable on computed tomography/magnetic resonance imaging (CT/MRI) scan per Response Evaluation Criteria on Solid Tumors (RECIST) v 1.1 (Eisenhauer 2009; Appendix C).
* Participants may have failed a programmed cell death protein 1 (PD-1) or programmed death-ligand 1 (PD-L1) therapy for advanced disease.
* Participants that are known to be epidermal growth factor (EGFR)-activating mutation positive must have received an EGFR inhibitor.
* Participants 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 participants 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Number of Dose Limiting Toxicities (DLTs)
timeFrame: Cycle 1 (Day 1 through Day 21) (1 Cycle = 21 days)
measure: Number of Participants With the Indicated Type of Adverse Events for PEGPH20 and Docetaxel
timeFrame: From date of first dose until 30 days after the last dose of study treatment, up to approximately 1 year 10 months
measure: Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of PEGPH20
timeFrame: Cycle 1 of Dose Escalation portion (Cycle 1 = 21 days)
Secondary outcomes:
measure: Phase 1b: Maximum Plasma Concentration (Cmax) of PEGPH20 and Docetaxel
timeFrame: PEGPH20: multiple time points C1D1 and all subsequent Cycles; Docetaxel: multiple time points C1D2, C2D2 and C3D2
measure: Phase 1b: Minimum Plasma Concentration (Cmin) of PEGPH20 and Docetaxel
timeFrame: PEGPH20: multiple time points C1D1 and all subsequent Cycles; Docetaxel: multiple time points C1D2, C2D2 and C3D2
measure: Phase 1b: Time to Maximum Plasma Concentration (Tmax) of PEGPH20 and Docetaxel
timeFrame: PEGPH20: multiple time points C1D1 and all subsequent Cycles; Docetaxel: multiple time points C1D2, C2D2 and C3D2
measure: Phase 1b: Terminal Half-life (t1/2) of PEGPH20 and Docetaxel
timeFrame: PEGPH20: multiple time points C1D1 and all subsequent Cycles; Docetaxel: multiple time points C1D2, C2D2 and C3D2
measure: Phase 1b: Area Under the Plasma Concentration-Time Curve for PEGPH20 and Docetaxel
timeFrame: PEGPH20: multiple time points C1D1 and all subsequent Cycles; Docetaxel: multiple time points C1D2, C2D2 and C3D2
measure: Phase 1b: Volume of Distribution (Vd) of PEGPH20 and Docetaxel
timeFrame: PEGPH20: multiple time points C1D1 and all subsequent Cycles; Docetaxel: multiple time points C1D2, C2D2 and C3D2
measure: Phase 1b: Clearance (CL) of PEGPH20 and Docetaxel
timeFrame: PEGPH20: multiple time points C1D1 and all subsequent Cycles; Docetaxel: multiple time points C1D2, C2D2 and C3D2
measure: Objective Response Rate (ORR)
timeFrame: From date of treatment start until disease progression or up to data cutoff date (30 Nov 2016), for up to approximately 1 year 9 months
measure: Disease Control Rate (DCR)
timeFrame: From date of treatment start until disease progression or up to data cutoff date (30 Nov 2016), for up to approximately 1 year 9 months
measure: Duration of Response (DoR)
timeFrame: From date of first CR or PR until the date of first documentation of disease progression or date of death, assessed up to data cutoff date (30 Nov 2016)
measure: Progression-free Survival (PFS)
timeFrame: From date of treatment start until date of first documentation of progressive disease or death from any cause, assessed up to 1 year 9 months
Other outcomes:
Locations:
city: Encinitas
country: United States
facility: California Cancer Associates for Research and Excellence (cCare)
state: California
city: Fresno
country: United States
facility: California Cancer Associates for Research and Excellence (cCare)
state: California
city: San Diego
country: United States
facility: Moores UCSD Cancer Center, Clinical Trials Office
state: California
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Charlotte
country: United States
facility: Levine Cancer Institute
state: North Carolina
city: Canton
country: United States
facility: Gabrail Cancer Center Research
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals of Cleveland
state: Ohio
Study officials:
References:
citation: Heineman T, Baumgart M, Nanavati C, Gabrail N, Van Wart SA, Mager DE, Maneval DC, Fathallah AM, Sekulovich RE. Safety and pharmacokinetics of docetaxel in combination with pegvorhyaluronidase alfa in patients with non-small cell lung cancer. Clin Transl Sci. 2021 Sep;14(5):1875-1885. doi: 10.1111/cts.13041. Epub 2021 Jul 30.