A Phase 1b Study of PEGylated Recombinant Human Hyaluronidase (PEGPH20) Combined With Docetaxel in Subjects With Recurrent Previously Treated Locally Advanced or Metastatic NSCLC

Non-small Cell Lung Cancer Clinical Trial

— PRIMAL  

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02346370
• Other study ID #: HALO-107-201
• Status: Terminated
• Phase: Phase 1
• Start date: February 10, 2015
• Est. completion date: November 14, 2016

Study information

• Verified date: February 2019
• Source: Halozyme Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 16
• Est. completion date: November 14, 2016
• Est. primary completion date: August 9, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-small Cell Lung Cancer

Intervention

Drug:
• PEGylated recombinant human hyaluronidase PH20

• Docetaxel

Locations

Country	Name	City	State
United States	Gabrail Cancer Center Research	Canton	Ohio
United States	Levine Cancer Institute	Charlotte	North Carolina
United States	University Hospitals of Cleveland	Cleveland	Ohio
United States	California Cancer Associates for Research and Excellence (cCare)	Encinitas	California
United States	California Cancer Associates for Research and Excellence (cCare)	Fresno	California
United States	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	University of Rochester	Rochester	New York
United States	Moores UCSD Cancer Center, Clinical Trials Office	San Diego	California

Sponsors (1)

Lead Sponsor	Collaborator
Halozyme Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Dose Limiting Toxicities (DLTs)	DLTs were defined as adverse events (AEs) that occurred during Cycle 1 in the Dose Escalation portion of the study, and deemed by the Investigator as related to study treatment.	Cycle 1 (Day 1 through Day 21) (1 Cycle = 21 days)
Primary	Number of Participants With the Indicated Type of Adverse Events for PEGPH20 and Docetaxel	Throughout the Treatment Period, the assessment of safety was based on AEs, including deaths, non-serious AEs, and serious adverse events, AEs leading to discontinuation of study treatment, and results of vital sign measurements and clinical laboratory assessments (including hematology, clinical chemistry, coagulation parameters, and urinalysis). Additionally, thromboembolic (TE) events were deemed by the Sponsor as AEs of special interest. AEs and laboratory values were graded for severity using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.	From date of first dose until 30 days after the last dose of study treatment, up to approximately 1 year 10 months
Primary	Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of PEGPH20		Cycle 1 of Dose Escalation portion (Cycle 1 = 21 days)
Secondary	Phase 1b: Maximum Plasma Concentration (Cmax) of PEGPH20 and Docetaxel	Blood samples were collected from all participants per protocol and analyzed for plasma PEGPH20 concentration using a validated electrochemiluminescence (ECL) immunoassay. Plasma docetaxel concentrations were analyzed using a validated liquid chromatography with tandem mass spectrometry assay (LS-MS/MS). The following blood draw schedule was used, PEGPH20: Cycle 1 Day 1 (C1D1) (predose, 15 minutes (min), 1, 2 to 4, and 24 hours (hr) postdose), C2 and all subsequent Cycles (predose, 1 hr postdose). Docetaxel: C1D2 (30 min after the start of the 1-hr infusion, 30 min post completion of the infusion, 4 to 6 and 24 hr post infusion), C1D3 (24 hr post infusion), C2D2 and C3D2 (30 min after the start of the 1-hour infusion, 30 min post completion of the infusion).	PEGPH20: multiple time points C1D1 and all subsequent Cycles; Docetaxel: multiple time points C1D2, C2D2 and C3D2
Secondary	Phase 1b: Minimum Plasma Concentration (Cmin) of PEGPH20 and Docetaxel	Blood samples were collected from all participants per protocol and analyzed for plasma PEGPH20 concentration using a validated ECL immunoassay. Plasma docetaxel concentrations were analyzed using a validated liquid chromatography with LS-MS/MS. The following blood draw schedule was used, PEGPH20: C1D1 (predose, 15 min, 1, 2 to 4, and 24 hr postdose), C2 and all subsequent Cycles (predose, 1 hr postdose). Docetaxel: C1D2 (30 min after the start of the 1-hr infusion, 30 min post completion of the infusion, 4 to 6 and 24 hr post infusion), C1D3 (24 hr post infusion), C2D2 and C3D2 (30 min after the start of the 1-hour infusion, 30 min post completion of the infusion).	PEGPH20: multiple time points C1D1 and all subsequent Cycles; Docetaxel: multiple time points C1D2, C2D2 and C3D2
Secondary	Phase 1b: Time to Maximum Plasma Concentration (Tmax) of PEGPH20 and Docetaxel	Blood samples were collected from all participants per protocol and analyzed for plasma PEGPH20 concentration using a validated ECL immunoassay. Plasma docetaxel concentrations were analyzed using a validated liquid chromatography with LS-MS/MS. The following blood draw schedule was used, PEGPH20: C1D1 (predose, 15 min, 1, 2 to 4, and 24 hr postdose), C2 and all subsequent Cycles (predose, 1 hr postdose). Docetaxel: C1D2 (30 min after the start of the 1-hr infusion, 30 min post completion of the infusion, 4 to 6 and 24 hr post infusion), C1D3 (24 hr post infusion), C2D2 and C3D2 (30 min after the start of the 1-hour infusion, 30 min post completion of the infusion).	PEGPH20: multiple time points C1D1 and all subsequent Cycles; Docetaxel: multiple time points C1D2, C2D2 and C3D2
Secondary	Phase 1b: Terminal Half-life (t1/2) of PEGPH20 and Docetaxel	Blood samples were collected from all participants per protocol and analyzed for plasma PEGPH20 concentration using a validated ECL immunoassay. Plasma docetaxel concentrations were analyzed using a validated liquid chromatography with LS-MS/MS. The following blood draw schedule was used, PEGPH20: C1D1 (predose, 15 min, 1, 2 to 4, and 24 hr postdose), C2 and all subsequent Cycles (predose, 1 hr postdose). Docetaxel: C1D2 (30 min after the start of the 1-hr infusion, 30 min post completion of the infusion, 4 to 6 and 24 hr post infusion), C1D3 (24 hr post infusion), C2D2 and C3D2 (30 min after the start of the 1-hour infusion, 30 min post completion of the infusion).	PEGPH20: multiple time points C1D1 and all subsequent Cycles; Docetaxel: multiple time points C1D2, C2D2 and C3D2
Secondary	Phase 1b: Area Under the Plasma Concentration-Time Curve for PEGPH20 and Docetaxel	Blood samples were collected from all participants per protocol and analyzed for plasma PEGPH20 concentration using a validated ECL immunoassay. Plasma docetaxel concentrations were analyzed using a validated liquid chromatography with LS-MS/MS. The following blood draw schedule was used, PEGPH20: C1D1 (predose, 15 min, 1, 2 to 4, and 24 hr postdose), C2 and all subsequent Cycles (predose, 1 hr postdose). Docetaxel: C1D2 (30 min after the start of the 1-hr infusion, 30 min post completion of the infusion, 4 to 6 and 24 hr post infusion), C1D3 (24 hr post infusion), C2D2 and C3D2 (30 min after the start of the 1-hour infusion, 30 min post completion of the infusion).	PEGPH20: multiple time points C1D1 and all subsequent Cycles; Docetaxel: multiple time points C1D2, C2D2 and C3D2
Secondary	Phase 1b: Volume of Distribution (Vd) of PEGPH20 and Docetaxel	Blood samples were collected from all participants per protocol and analyzed for plasma PEGPH20 concentration using a validated ECL immunoassay. Plasma docetaxel concentrations were analyzed using a validated liquid chromatography with LS-MS/MS. The following blood draw schedule was used, PEGPH20: C1D1 (predose, 15 min, 1, 2 to 4, and 24 hr postdose), C2 and all subsequent Cycles (predose, 1 hr postdose). Docetaxel: C1D2 (30 min after the start of the 1-hr infusion, 30 min post completion of the infusion, 4 to 6 and 24 hr post infusion), C1D3 (24 hr post infusion), C2D2 and C3D2 (30 min after the start of the 1-hour infusion, 30 min post completion of the infusion).	PEGPH20: multiple time points C1D1 and all subsequent Cycles; Docetaxel: multiple time points C1D2, C2D2 and C3D2
Secondary	Phase 1b: Clearance (CL) of PEGPH20 and Docetaxel	Blood samples were collected from all participants per protocol and analyzed for plasma PEGPH20 concentration using a validated ECL immunoassay. Plasma docetaxel concentrations were analyzed using a validated liquid chromatography with LS-MS/MS. The following blood draw schedule was used, PEGPH20: C1D1 (predose, 15 min, 1, 2 to 4, and 24 hr postdose), C2 and all subsequent Cycles (predose, 1 hr postdose). Docetaxel: C1D2 (30 min after the start of the 1-hr infusion, 30 min post completion of the infusion, 4 to 6 and 24 hr post infusion), C1D3 (24 hr post infusion), C2D2 and C3D2 (30 min after the start of the 1-hour infusion, 30 min post completion of the infusion).	PEGPH20: multiple time points C1D1 and all subsequent Cycles; Docetaxel: multiple time points C1D2, C2D2 and C3D2
Secondary	Objective Response Rate (ORR)	ORR = complete response + partial response (CR + PR)	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
Secondary	Disease Control Rate (DCR)		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
Secondary	Duration of Response (DoR)		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)
Secondary	Progression-free Survival (PFS)		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