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

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ClinicalTrials.gov Identifier: NCT01959139
Recruitment Status : Active, not recruiting
First Posted : October 9, 2013
Last Update Posted : June 1, 2018
Sponsor:
Collaborators:
National Cancer Institute (NCI)
Halozyme Therapeutics
Information provided by (Responsible Party):
Southwest Oncology Group

Brief 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.

Condition or disease Intervention/treatment Phase
Metastatic Pancreatic Adenocarcinoma Drug: PEGPH20 Drug: Oxaliplatin Drug: Leucovorin Drug: Irinotecan Drug: 5-fluorouracil Phase 1 Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 172 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : January 2014
Estimated Primary Completion Date : April 2019
Estimated Study Completion Date : October 2020

Arm Intervention/treatment
Active Comparator: Phase II: mFOLFIRINOX
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 5-fluorouracil (5-FU) IV over 46 hours on days 2-4. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Drug: Oxaliplatin
85 mg/m^2, on Day 2, IV over 2 hours
Other Names:
  • Eloxatin
  • NSC-266046

Drug: Leucovorin
400 mg/m^2, on Day 2, IV over 2 hours
Other Name: leucovorin calcium

Drug: Irinotecan
180 mg/m^2, on Day 2, IV over 1.5 hours
Other Names:
  • CPT-11
  • NSC-616348

Drug: 5-fluorouracil
2,400 mg/m^2, Days 2-4, IV over 46 hours
Other Names:
  • 5-FU
  • Adrucil
  • NSC-19893

Experimental: Phase II: mFOLFIRINOX + PEGPH20
Patients receive pegylated recombinant human hyaluronidase (PEGPH20) IV over 10 minutes on day 1 and oxaliplatin, leucovorin calcium, irinotecan hydrochloride, and 5-fluorouracil (5-FU) as in Arm I. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Drug: PEGPH20
3 ug/kg on Day 1, IV over 15 minutes
Other Name: Pegylated Recombinant Human Hyaluronidase

Drug: Oxaliplatin
85 mg/m^2, on Day 2, IV over 2 hours
Other Names:
  • Eloxatin
  • NSC-266046

Drug: Leucovorin
400 mg/m^2, on Day 2, IV over 2 hours
Other Name: leucovorin calcium

Drug: Irinotecan
180 mg/m^2, on Day 2, IV over 1.5 hours
Other Names:
  • CPT-11
  • NSC-616348

Drug: 5-fluorouracil
2,400 mg/m^2, Days 2-4, IV over 46 hours
Other Names:
  • 5-FU
  • Adrucil
  • NSC-19893

Experimental: Phase I
PEGPH20, 3 ug/kg on Day 1 and Day 3/4, 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 (5-FU), 2,400 mg/m^2, Days 2-4, IV over 46 hours
Drug: PEGPH20
3 ug/kg on Day 1, IV over 15 minutes
Other Name: Pegylated Recombinant Human Hyaluronidase

Drug: Oxaliplatin
85 mg/m^2, on Day 2, IV over 2 hours
Other Names:
  • Eloxatin
  • NSC-266046

Drug: Leucovorin
400 mg/m^2, on Day 2, IV over 2 hours
Other Name: leucovorin calcium

Drug: Irinotecan
180 mg/m^2, on Day 2, IV over 1.5 hours
Other Names:
  • CPT-11
  • NSC-616348

Drug: 5-fluorouracil
2,400 mg/m^2, Days 2-4, IV over 46 hours
Other Names:
  • 5-FU
  • Adrucil
  • NSC-19893




Primary Outcome Measures :
  1. Phase I: Maximum tolerated dose of PEGPH20, determined according to incidence of dose-limiting toxicity graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4 [ Time Frame: 28 days ]
    Assess safety of mFOLFIRINOX in combination with PEGPH20 and select the optimal dose of PEGPH20 for the Phase II portion.

  2. Phase II: Overall Survival [ Time Frame: From date of registration to date of death due to any cause, assessed up to 3 years ]
    Assessed using the logrank test.


Secondary Outcome Measures :
  1. Progression Free Survival (PFS) (Phase II) [ Time Frame: From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause, assessed up to 3 years ]
  2. Objective Tumor Response (confirmed and unconfirmed, complete and partial) [ Time Frame: Up to 3 years ]
  3. Frequency of adverse events [ Time Frame: Up to 3 years ]
  4. Severity of adverse events [ Time Frame: Up to 3 years ]
  5. Tolerability of adverse events [ Time Frame: Up to 3 years ]

Other Outcome Measures:
  1. Carbohydrate Antigen (CA) 19-9 Levels [ Time Frame: Within 2 years of the end of the study ]
    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.

  2. Plasma expression of hyaluronan (HA) [ Time Frame: Within 2 years of end of study ]
  3. Tumor expression of HA [ Time Frame: Within 2 years of end of study ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01959139


  Show 154 Study Locations
Sponsors and Collaborators
Southwest Oncology Group
National Cancer Institute (NCI)
Halozyme Therapeutics
Investigators
Study Chair: Ramesh K Ramanathan, M.D. Virginia G. Piper Cancer Center

Responsible Party: Southwest Oncology Group
ClinicalTrials.gov Identifier: NCT01959139     History of Changes
Other Study ID Numbers: S1313
NCI-2013-01776 ( Other Identifier: NCI )
U10CA180888 ( U.S. NIH Grant/Contract )
S1313 ( Other Identifier: SWOG )
First Posted: October 9, 2013    Key Record Dates
Last Update Posted: June 1, 2018
Last Verified: May 2018

Additional relevant MeSH terms:
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Calcium, Dietary
Oxaliplatin
Irinotecan
Fluorouracil
Levoleucovorin
Leucovorin
Bone Density Conservation Agents
Physiological Effects of Drugs
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimetabolites
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Antidotes
Protective Agents
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances