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A Phase 1b/2, Study of Pegylated Recombinant Human Hyaluronidase Combined With Docetaxel Versus Docetaxel Alone in Subjects With Recurrent Previously Treated Locally Advanced or Metastatic NSCLC.

Information source: Halozyme Therapeutics
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Non Small Cell Lung Cancer

Intervention: PEGPH20 (Drug); Docetaxel (Drug)

Phase: Phase 1/Phase 2

Status: Recruiting

Sponsored by: Halozyme Therapeutics

Official(s) and/or principal investigator(s):
Samuel Dychter, MD, Study Director, Affiliation: Halozyme Therapeutics

Overall contact:
Samuel Dychter, MD, Phone: 858-794-8889, Email: sdychter@halozyme.com

Summary

A Phase 1b/2 study for patients with Stage IIIB/IV NSCLC to participate in one of three portions of this study. The first portion is dose escalation in which subjects are tested with PEGPH20 at various doses (1. 6, 3. 0, 4. 0, 5. 3 and 7. 0 ug/kg) and dosing schedules (either once every 21 day cycle or twice/week or 6 times/21 day cycle) plus a standard dose of docetaxel (75mg/m2 once every 3 weeks) until the MTD (maximum tolerated dose) is reached in both dosing schedules. The second portion is a randomized schedule finding component in which the MTDs of both dosing schedules are tested (approximately 25-30 subjects) and the most safe, efficacious and tolerated dose/schedule is chosen to be tested in the Phase 2 portion. Phase 2 will compare the selected dose schedule of PEGPH20 plus docetaxel with docetaxel alone.

Clinical Details

Official title: PRIMAL STUDY: A Phase 1b/2, Randomized, Multicenter, Multinational Study of Pegylated Recombinant Human Hyaluronidase (PEGPH20) Combined With Docetaxel (PDoc) Compared With Docetaxel (Doc) Alone in Subjects With Recurrent Previously Treated Locally Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC)

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome:

Phase 1 B - Dose limiting toxicities

Phase 1B - Maximum Tolerated Dose(s)

Phase 1B - Optimal PEGPH20-Docetaxel (PDoc) dosage

Phase 2 - PFS (Progression Free Survival) for PEG PH20 plus Docetaxel compared with Docetaxel alone in high HA population

Secondary outcome:

Phase 1B - PK Parameters for PEGPH20 and docetaxel: Maximum observed concentration, Cmax, Cmin, tmax, terminal 1/2 life, AUC (area under the curve), volume of distribution and Clearance.

Phase 1B - ORR (Objective Response Rate)

Phase 2 - ORR (Objective Response Rate) for PDoc compared with Doc alone in high HA population

Phase 2 - Safety endpoints such as adverse events, physical exam and lab data

Phase 2 - DOR (Duration of Response) for PDoc compared with Doc alone in high HA population.

Phase 2 - DCR (Disease Control Rate) for PDoc compared with Doc alone in high HA population

OS (Overall Survival) for PDoc compared with Doc alone in high HA population

Detailed description: This is a Phase 1b/2 study for subjects with Stage IIIB/IV NSCLC to participate in one of three portions of this study. The first portion of the Phase 1b is dose escalation which will enroll approximating 20-30 subjects testing various dose levels of PEGPH20 (1. 6, 3. 0, 4. 0, 5. 3 and 7. 0 ug/kg) plus docetaxel 75mg/m2 once every 3 weeks until the MTD is found for both dosing schedules (Schedule A, PEGPH20 plus docetaxel every 21 day cycle and Schedule B, PEGPH20 twice per week/per 21 day cycle or 6 times/cycle) plus docetaxel (once every 3 weeks) . The second portion of the phase 1b is the Schedule finding component. This portion will enroll approximately 25-30 subjects and will randomize (1: 1) approximately 10 subjects in each schedule (Schedule A or B) at the MTD dose. After the Phase 1b is completed, all data will be analyzed and the most safe, best tolerated and most efficacious dose and schedule of PEGPH20 plus docetaxel (PDoc) will be used in the Phase 2 portion. In Phase 2, approximately 188 subjects will be enrolled and randomized 1: 1 to receive PEGPH20 plus docetaxel (75mg/m2) or docetaxel (75mg/m2) alone. Subjects in both the Schedule finding and Phase 2 portions of the study will be pre-selected for high levels of hyaluronan (HA) in tumor tissue during screening. Subjects must have failed a platinum based therapy (1st line). Subjects to remain on study as long as tolerated, until disease progression or experience an adverse event.

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Signed, approved Informed Consent

- Histologically confirmed and previously treated Stage IIIB/IV NSCLC, having failed no

more than 1 platinum chemo regimen

- Available archival tumor tissue block - 10 unstained, core biopsy slides that meet

specific tissue requirements

- Phase 1b Schedule finding/Phase 2 - one or more tumors measureable on CT scan (RECIST

1. 1)

- Life expectancy - =/> 3 months, ECOG (Eastern Cooperative Oncology Group) status = 0

or 1

- Negative pregnancy test

- Men and women agreement to use effective contraceptive method

- Specific ranges/levels of Screening labs that are acceptable

Exclusion Criteria:

- Previous treatment with docetaxel

- New York Heart Assoc Class III or IV cardiac disease, myocardial infarction within

the past 12 - months

- Prior history of cerebrovascular accident or transient ischemic attack or preexisting

- carotid artery disease

- History of pulmonary embolism or pulmonary embolism found on screening exam

- Active, uncontrolled bacterial, viral or fungal infection at time of screening

- Known infection with HIV, 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

- Women currently pregnant or breast feeding

- Intolerance to dexamethasone as determined by Investigator

- History of another primary cancer within the last 3 years

- 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. Subject's inability to

comply with study and follow-up procedures, as judged by the Investigator

Locations and Contacts

Samuel Dychter, MD, Phone: 858-794-8889, Email: sdychter@halozyme.com

California Cancer Associates for Research and Excellence (cCare), Encinitas, California 92024, United States; Recruiting
Alberto Bessudo, MD, Principal Investigator

California Cancer Associates for Research and Excellence (cCare), Fresno, California 93720, United States; Recruiting
Steven J Hager, DO, Principal Investigator

Moores UCSD Cancer Center, Clinical Trials Office, San Diego, California 92093, United States; Recruiting
Lyudmila Bazhenova, MD, Principal Investigator

Pacific Hematology Oncology Associates, San Francisco, California 94115, United States; Recruiting
D
Ari D Baron, MD, Principal Investigator

Norton Cancer Institute, Louisville, Kentucky 40202, United States; Recruiting
John Hamm, MD, Principal Investigator

Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire 03756, United States; Recruiting
Konstantin H Dragnev, MD, Principal Investigator

University of Rochester, Rochester, New York 14642, United States; Recruiting
Eric Kim, MD, Principal Investigator

Levine Cancer Institute, Charlotte, North Carolina 28112, United States; Recruiting
Daniel Haggstrom, MD, Principal Investigator

Gabrail Cancer Center Research, Canton, Ohio 44718-2566, United States; Recruiting
Nashat Y Gabrail, MD, Principal Investigator

University Hospitals of Cleveland, Cleveland, Ohio 44106, United States; Recruiting
Afshin Dowlati, MD, Principal Investigator

Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania 17033, United States; Recruiting
Chandra Belani, MD, Principal Investigator

Tennessee Cancer Specialists, Knoxville, Tennessee 37909, United States; Recruiting
Tracy W Dobbs, MD, Principal Investigator

Additional Information

Starting date: December 2014
Last updated: August 10, 2015

Page last updated: August 23, 2015

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