S1313, PEGPH20 in Treating Patients With Newly Diagnosed Metastatic Pancreatic Cancer

Metastatic Pancreatic Adenocarcinoma Clinical Trial

Official title:

S1313, A Phase IB/II Randomized Study of Modified FOLFIRINOX + Pegylated Recombinant Human Hyaluronidase (PEGPH20) Versus Modified FOLFIRINOX Alone in Patients With Good Performance Status Metastatic Pancreatic Adenocarcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01959139
• Other study ID #: S1313
• Secondary ID: NCI-2013-01776U1
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: January 23, 2014
• Est. completion date: November 9, 2023

Study information

• Verified date: February 2024
• Source: SWOG Cancer Research Network
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This partially randomized phase I/II trial studies the side effects and best dose of pegylated recombinant human hyaluronidase (PEGPH20) when given together with combination chemotherapy and to see how well they work compared with combination chemotherapy alone in treating patients with newly diagnosed pancreatic cancer that has spread to other places in the body. Pegylated recombinant human hyaluronidase may help chemotherapy drugs work better by making tumor cells more sensitive to the drugs. Drugs used in chemotherapy, such as leucovorin calcium, fluorouracil, irinotecan hydrochloride, and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether combination chemotherapy is more effective with or without pegylated recombinant human hyaluronidase in treating pancreatic cancer.

Description:

PRIMARY OBJECTIVES: I. To assess the safety of modified leucovorin calcium, fluorouracil, irinotecan hydrochloride and oxaliplatin (mFOLFIRINOX) in combination with PEGPH20 and select the optimal dose of PEGPH20 for the phase II portion in patients with metastatic pancreatic adenocarcinoma. (Phase I) II. To assess the overall survival of patients with metastatic pancreatic adenocarcinoma treated with mFOLFIRINOX + PEGPH20 compared to those treated with mFOLFIRINOX alone. (Phase II) SECONDARY OBJECTIVES: I. To assess progression free survival (PFS) in patients receiving mFOLFIRINOX with PEGPH20 and patients receiving mFOLFIRINOX alone in this patient population. II. To assess objective tumor response (confirmed and unconfirmed, complete and partial) in patients with measurable disease treated with mFOLFIRINOX with PEGPH20 and patients receiving mFOLFIRINOX alone in this patient population. III. To determine the frequency, severity, and tolerability of adverse events of mFOLFIRINOX with PEGPH20. TERTIARY OBJECTIVES: I. To explore the correlation of maximum decrease in cancer antigen (CA) 19-9 levels and time to maximum decrease in CA 19-9 levels with overall survival, progression-free survival and response. II. To explore the correlation of plasma hyaluronan (HA) and tumor expression of HA with overall survival, progression-free survival and response. OUTLINE: This is a phase I, dose de-escalation study of pegylated recombinant human hyaluronidase followed by a randomized phase II study. PHASE I: Patients receive pegylated recombinant human hyaluronidase intravenously (IV) over 10 minutes on day 1*; oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and irinotecan hydrochloride IV over 1.5 hours on day 2; and fluorouracil IV over 46 hours on days 2-4. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. PHASE II: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and irinotecan hydrochloride IV over 1.5 hours on day 2, and fluorouracil IV over 46 hours on days 2-4. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive pegylated recombinant human hyaluronidase IV over 10 minutes on day 1* and oxaliplatin, leucovorin calcium, irinotecan hydrochloride, and fluorouracil as in Arm I. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. *NOTE: Some patients also receive pegylated recombinant human hyaluronidase on day 3 or 4 of courses 1 and 2. After completion of study treatment, patients are followed up for 3 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 126
• Est. completion date: November 9, 2023
• Est. primary completion date: April 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

• Patients must have newly diagnosed, untreated metastatic histologically or cytologically documented pancreatic adenocarcinoma; patients must not have known history of brain metastases
• Patients must have measurable metastatic disease; computed tomography (CT) scans or magnetic resonance imaging (MRI)s used to assess measurable disease must have been completed within 28 days prior to registration; CT scans or MRIs used to assess non-measurable disease must have been completed within 42 days prior to registration; CT scans or MRIs must be assessed and documented on the Baseline Tumor Assessment Form (Response Evaluation Criteria in Solid Tumors [RECIST] 1.1)
• Patients must not have had any prior treatment with oxaliplatin or irinotecan within 3 years prior to registration; patients must not have had prior chemotherapy in metastatic setting; prior abdominal radiation therapy is not allowed
• Patients must have a Zubrod performance status of 0-1
• Absolute neutrophil count (ANC) >= 1,500/mcL
• Platelets >= 100,000/mcL
• Hemoglobin >= 9 g/dL
• Total bilirubin =< institutional upper limit of normal (IULN)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) both =< 2.5 X IULN in the absence of liver metastases or =< 5.0 x IULN with liver metastasis
• Serum albumin >= 3 g/dL
• Serum creatinine =< ULN within 14 days prior to registration OR calculated creatinine clearance > 50 ml/min; the serum creatinine value used in the calculation must have been obtained within 14 days prior to registration
• Patients must have international normalized ratio (INR) =< 1.2 within 14 days prior to registration; patients must not be receiving warfarin for therapeutic use, have history of cerebrovascular accident (CVA), history of transient ischemic attack (TIA) requiring intervention or treatment, pre-existing carotid artery disease requiring intervention or treatment, or current use of megestrol acetate (use within 10 days of registration)
• Patients must not be receiving chronic treatment (equivalent of prednisone > 10 mg/day) with systemic steroids or other immuno-suppressive agent
• Patients must not have liver disease such a cirrhosis, chronic active hepatitis or chronic persistent hepatitis
• Patients must not have active bleeding or a pathological condition that is associated with a high risk of bleeding
• Patients with a known history of human immunodeficiency virus (HIV) must not be on active treatment for HIV
• Patients must have no non-malignant medical illnesses that are uncontrolled or whose control may be jeopardized by the treatment with protocol therapy
• No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for five years
• Patients must not be pregnant or nursing; women/men of reproductive potential must have agreed to use an effective contraceptive method; a woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months; in addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation; if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures
• Patients must have tumor (paraffin block or slides) available for submission and be willing to submit tumor and blood samples
• Patients or their legally authorized representative must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines
• As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
• Patients planning to enroll in the phase I portion of this study must first have a slot reserved in advance of the registration; all site staff will use OPEN to create a slot reservation

Related Conditions & MeSH terms

• Adenocarcinoma
• Metastatic Pancreatic Adenocarcinoma

Intervention

Drug:
• PEGPH20
3 ug/kg on Day 1, IV over 15 minutes
• Oxaliplatin
85 mg/m^2, on Day 2, IV over 2 hours
• Leucovorin
400 mg/m^2, on Day 2, IV over 2 hours
• Irinotecan
180 mg/m^2, on Day 2, IV over 1.5 hours
• 5-fluorouracil
2,400 mg/m^2, Days 2-4, IV over 46 hours

Locations

Country	Name	City	State
United States	Providence Regional Cancer System-Aberdeen	Aberdeen	Washington
United States	Cancer Care Center at Island Hospital	Anacortes	Washington
United States	Alaska Breast Care and Surgery LLC	Anchorage	Alaska
United States	Alaska Women's Cancer Care	Anchorage	Alaska
United States	Anchorage Associates in Radiation Medicine	Anchorage	Alaska
United States	Katmai Oncology Group	Anchorage	Alaska
United States	Providence Alaska Medical Center	Anchorage	Alaska
United States	Randolph Hospital	Asheboro	North Carolina
United States	Sutter Auburn Faith Hospital	Auburn	California
United States	Sutter Cancer Centers Radiation Oncology Services-Auburn	Auburn	California
United States	PeaceHealth Saint Joseph Medical Center	Bellingham	Washington
United States	Saint Charles Health System	Bend	Oregon
United States	Alta Bates Summit Medical Center-Herrick Campus	Berkeley	California
United States	Illinois CancerCare-Bloomington	Bloomington	Illinois
United States	Saint Joseph Medical Center	Bloomington	Illinois
United States	Saint Luke's Mountain States Tumor Institute	Boise	Idaho
United States	Parkland Health Center-Bonne Terre	Bonne Terre	Missouri
United States	Providence Saint Joseph Medical Center/Disney Family Cancer Center	Burbank	California
United States	Mills - Peninsula Hospitals	Burlingame	California
United States	Cone Health Cancer Center at Alamance Regional	Burlington	North Carolina
United States	Sutter Cancer Centers Radiation Oncology Services-Cameron Park	Cameron Park	California
United States	Illinois CancerCare-Canton	Canton	Illinois
United States	Saint Francis Medical Center	Cape Girardeau	Missouri
United States	Southeast Cancer Center	Cape Girardeau	Missouri
United States	Memorial Hospital of Carbondale	Carbondale	Illinois
United States	Illinois CancerCare-Carthage	Carthage	Illinois
United States	Eden Hospital Medical Center	Castro Valley	California
United States	Centralia Oncology Clinic	Centralia	Illinois
United States	Providence Regional Cancer System-Centralia	Centralia	Washington
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Clackamas Radiation Oncology Center	Clackamas	Oregon
United States	Providence Oncology and Hematology Care Southeast	Clackamas	Oregon
United States	Southeastern Medical Oncology Center-Clinton	Clinton	North Carolina
United States	Bay Area Hospital	Coos Bay	Oregon
United States	City of Hope Corona	Corona	California
United States	UC Irvine Health Cancer Center-Newport	Costa Mesa	California
United States	Sutter Davis Hospital	Davis	California
United States	Cancer Care Center of Decatur	Decatur	Illinois
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	Smilow Cancer Hospital-Derby Care Center	Derby	Connecticut
United States	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Swedish Medical Center-Edmonds	Edmonds	Washington
United States	Crossroads Cancer Center	Effingham	Illinois
United States	Illinois CancerCare-Eureka	Eureka	Illinois
United States	Providence Regional Cancer Partnership	Everett	Washington
United States	Smilow Cancer Hospital Care Center-Fairfield	Fairfield	Connecticut
United States	Weisberg Cancer Treatment Center	Farmington Hills	Michigan
United States	Saint Luke's Mountain States Tumor Institute - Fruitland	Fruitland	Idaho
United States	Illinois CancerCare-Galesburg	Galesburg	Illinois
United States	Western Illinois Cancer Treatment Center	Galesburg	Illinois
United States	Southeastern Medical Oncology Center-Goldsboro	Goldsboro	North Carolina
United States	Wayne Memorial Hospital	Goldsboro	North Carolina
United States	Cone Health Cancer Center	Greensboro	North Carolina
United States	Medical Oncology and Hematology Group PC-Guilford	Guilford	Connecticut
United States	Smilow Cancer Hospital Care Center at Saint Francis	Hartford	Connecticut
United States	Hendersonville Hematology and Oncology at Pardee	Hendersonville	North Carolina
United States	Margaret R Pardee Memorial Hospital	Hendersonville	North Carolina
United States	Centerpoint Medical Center LLC	Independence	Missouri
United States	Swedish Cancer Institute-Issaquah	Issaquah	Washington
United States	Southeastern Medical Oncology Center-Jacksonville	Jacksonville	North Carolina
United States	Capital Region Medical Center-Goldschmidt Cancer Center	Jefferson City	Missouri
United States	Heartland Hematology and Oncology Associates Incorporated	Kansas City	Missouri
United States	Research Medical Center	Kansas City	Missouri
United States	Saint Luke's Hospital of Kansas City	Kansas City	Missouri
United States	Kadlec Clinic Hematology and Oncology	Kennewick	Washington
United States	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois
United States	Seattle Cancer Care Alliance at EvergreenHealth	Kirkland	Washington
United States	Providence Regional Cancer System-Lacey	Lacey	Washington
United States	Saint Luke's East - Lee's Summit	Lee's Summit	Missouri
United States	Kansas Institute of Medicine Cancer and Blood Center	Lenexa	Kansas
United States	Minimally Invasive Surgery Hospital	Lenexa	Kansas
United States	Liberty Radiation Oncology Center	Liberty	Missouri
United States	PeaceHealth Saint John Medical Center	Longview	Washington
United States	Los Angeles County-USC Medical Center	Los Angeles	California
United States	USC / Norris Comprehensive Cancer Center	Los Angeles	California
United States	Illinois CancerCare-Macomb	Macomb	Illinois
United States	Fremont - Rideout Cancer Center	Marysville	California
United States	Cone Heath Cancer Center at Mebane	Mebane	North Carolina
United States	Saint Luke's Mountain States Tumor Institute - Meridian	Meridian	Idaho
United States	Memorial Medical Center	Modesto	California
United States	Palo Alto Medical Foundation-Camino Division	Mountain View	California
United States	Palo Alto Medical Foundation-Gynecologic Oncology	Mountain View	California
United States	Saint Luke's Mountain States Tumor Institute - Nampa	Nampa	Idaho
United States	Smilow Cancer Center/Yale-New Haven Hospital	New Haven	Connecticut
United States	Yale University	New Haven	Connecticut
United States	Providence Newberg Medical Center	Newberg	Oregon
United States	Yale-New Haven Hospital North Haven Medical Center	North Haven	Connecticut
United States	Sutter Cancer Research Consortium	Novato	California
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Smilow Cancer Hospital-Orange Care Center	Orange	Connecticut
United States	UC Irvine Health/Chao Family Comprehensive Cancer Center	Orange	California
United States	Providence Willamette Falls Medical Center	Oregon City	Oregon
United States	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois
United States	Radiation Oncology of Northern Illinois	Ottawa	Illinois
United States	Menorah Medical Center	Overland Park	Kansas
United States	Saint Luke's South Hospital	Overland Park	Kansas
United States	Palo Alto Medical Foundation Health Care	Palo Alto	California
United States	Illinois CancerCare-Pekin	Pekin	Illinois
United States	OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center	Pekin	Illinois
United States	Illinois CancerCare-Peoria	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	OSF Saint Francis Medical Center	Peoria	Illinois
United States	OSF Saint Francis Radiation Oncology at Peoria Cancer Center	Peoria	Illinois
United States	Illinois CancerCare-Peru	Peru	Illinois
United States	Valley Radiation Oncology	Peru	Illinois
United States	Providence Portland Medical Center	Portland	Oregon
United States	Providence Saint Vincent Medical Center	Portland	Oregon
United States	Kansas City NCI Community Oncology Research Program	Prairie Village	Kansas
United States	Illinois CancerCare-Princeton	Princeton	Illinois
United States	Annie Penn Memorial Hospital	Reidsville	North Carolina
United States	Sutter Cancer Centers Radiation Oncology Services-Roseville	Roseville	California
United States	Sutter Roseville Medical Center	Roseville	California
United States	Sutter General Hospital	Sacramento	California
United States	University of California Davis Comprehensive Cancer Center	Sacramento	California
United States	Heartland Regional Medical Center	Saint Joseph	Missouri
United States	Missouri Baptist Medical Center	Saint Louis	Missouri
United States	Sainte Genevieve County Memorial Hospital	Sainte Genevieve	Missouri
United States	California Pacific Medical Center-Pacific Campus	San Francisco	California
United States	Palo Alto Medical Foundation-Santa Cruz	Santa Cruz	California
United States	Sutter Pacific Medical Foundation	Santa Rosa	California
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Group Health Cooperative-Seattle	Seattle	Washington
United States	Minor and James Medical PLLC	Seattle	Washington
United States	Pacific Gynecology Specialists	Seattle	Washington
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	Swedish Medical Center-Ballard Campus	Seattle	Washington
United States	Swedish Medical Center-First Hill	Seattle	Washington
United States	University of Washington Medical Center	Seattle	Washington
United States	Providence Regional Cancer System-Shelton	Shelton	Washington
United States	Rockwood Cancer Treatment Center-DHEC-Downtown	Spokane	Washington
United States	Rockwood Clinic Cancer Treatment Center-Valley	Spokane Valley	Washington
United States	Central Illinois Hematology Oncology Center	Springfield	Illinois
United States	Memorial Medical Center	Springfield	Illinois
United States	Southern Illinois University School of Medicine	Springfield	Illinois
United States	Springfield Clinic	Springfield	Illinois
United States	Missouri Baptist Sullivan Hospital	Sullivan	Missouri
United States	Palo Alto Medical Foundation-Sunnyvale	Sunnyvale	California
United States	Missouri Baptist Outpatient Center-Sunset Hills	Sunset Hills	Missouri
United States	Cancer Care Specialists of Illinois-Swansea	Swansea	Illinois
United States	Charlotte Hungerford Hospital Center for Cancer Care	Torrington	Connecticut
United States	Gene Upshaw Memorial Tahoe Forest Cancer Center	Truckee	California
United States	Smilow Cancer Hospital Care Center-Trumbull	Trumbull	Connecticut
United States	The University of Arizona Medical Center-University Campus	Tucson	Arizona
United States	University of Arizona Cancer Center-North Campus	Tucson	Arizona
United States	Saint Luke's Mountain States Tumor Institute-Twin Falls	Twin Falls	Idaho
United States	Sutter Cancer Centers Radiation Oncology Services-Vacaville	Vacaville	California
United States	Sutter Solano Medical Center/Cancer Center	Vallejo	California
United States	PeaceHealth Southwest Medical Center	Vancouver	Washington
United States	Providence Saint Mary Regional Cancer Center	Walla Walla	Washington
United States	Smilow Cancer Hospital-Waterbury Care Center	Waterbury	Connecticut
United States	City of Hope West Covina	West Covina	California
United States	Southeastern Medical Oncology Center-Wilson	Wilson	North Carolina
United States	Providence Regional Cancer System-Yelm	Yelm	Washington

Sponsors (3)

Lead Sponsor	Collaborator
SWOG Cancer Research Network	Halozyme Therapeutics, National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Cancer Antigen (CA) 19-9 Levels	Explore correlation of maximum decrease in CA 19-9 levels to maximum decrease in CA 19-9 levels with overall survival, progression-free survival and response.	Within 2 years of the end of the study
Other	Plasma Expression of Hyaluronan (HA)		Within 2 years of end of study
Other	Tumor Expression of HA		Within 2 years of end of study
Primary	Phase I: Maximum Tolerated Dose (MTD) of PEGPH20 in Combination With mFOLFIRINOX	Assess safety of mFOLFIRINOX in combination with PEGPH20 and select the optimal dose of PEGPH20 for the Phase II portion.; MTD of PEGPH20 in combination with mFOLFORINOX was evaluated by testing decreasing doses of PEGPH20 from 3mcg/kg on Day 1 and Day 3/4, to 3mcg/kg on Day 1 only and to 1.6 mcg/kg on Day 1 only.; MTD reflects the highest dose that had a dose-limiting toxicity (DLT) rate of = 17%. DLTs were defined as treatment regimen related: grade = 3 non-hematologic toxicity; grade 4 absolute neutrophil count (ANC) anemia or thrombocytopenia; grade 4 ANC lasting > 7 days; grade = 3 febrile neutropenia; grade = 3 elevation of aspartate aminotransferase (AST)/alanine aminotransferase (ALT), total bilirubin, and creatinine; delay in starting the 2nd cycle of mFOLFIRINOX by > 2 weeks due to drug related toxicity.; DLT were graded using the NCI CTCAE version 4. Note: the third and lowest dose level was not reached.	2 cycles of 14 days
Primary	Phase II: Overall Survival	Time from date of registration to date of death due to any cause. Participants last known to be alive are censored at date of last contact.; Assessed using the logrank test.	From date of registration to date of death due to any cause, assessed up to 3 years
Secondary	Progression Free Survival (PFS) (Phase II)	Time from date of registration to date of first documentation of progression or symptomatic deterioration or death due to any cause. Participants last known to be alive without report of progression are censored at date of last contact.	From date of registration to date of death due to any cause, assessed up to 3 years
Secondary	Objective Tumor Response Rate (Confirmed and Unconfirmed, Complete and Partial)	Objective tumor response rate (complete response, unconfirmed complete response, partial response, unconfirmed partial response) in patients with measurable disease were assessed in each arm and compared between arms using Chi-squared test.; Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions	Up to 3 years
Secondary	Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs	Adverse Events (AEs) are reported by CTCAE Version 4.0. Only adverse events that are possibly, probably or definitely related to study drug are reported.; Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living e.g. bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not bedridden.; Grade 4: Life-threatening consequences; urgent intervention indicated.; Grade 5: Death related to adverse event	Duration of treatment and follow up until death or 3 years post registration