800-872-2273

Clinical Trials and Studies

Your participation matters. Help us discover and cure!

Contact us at (800) USC-CARE (800-872-2273)

We're sorry, but this trial is no longer enrolling volunteers.

SWOG-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.

Description

The outcome of patients with metastatic pancreatic cancer remains very poor. Until recently, gemcitabine was the only agent with reproducible activity and resulting in a median survival of only 5-6 months. Despite attempts to improve the outcome by adding a second agent to gemcitabine, no worthwhile progress has been made thus far. There are grounds for optimism as two new regimens (gemcitabine/nab-paclitaxel and FOLFIRINOX) have emerged as front line options. The study drug, recombinant pegylated human hyaluronidase (PEGPH20) is widely used to enhance subcutaneous dispersion and absorption of various agents. It has shown to inhibit tumor growth, and enhance effects of chemotherapy in mouse models of cancer. Plus, other studies have shown the PEGPH20 can damage the outer layer of a tumor which can let more chemotherapy reach the tumor and possibly increase effectiveness. The study will be conducted in two sequential parts. A participant may be enrolled to either the Phase I Portion or the Phase II Portion. The Phase I portion will be a dose de-escalation clinical trial with two dose levels of PEGPH20. For the Phase II portion of the study (which will be temporarily closed to define the dose of PEGPH20) will have two treatment arms (Arm 1-mFolfirinox and Arm 2-PEGPH20+mFolfirinox). All study participants will be followed until death or 3 years after registration. The primary Phase 1 objective is to assess the safety of mFOLFIRINOX in combination with PEGPH20 and select the optimal dose of PEGPH20 for the Phase II portion in patients with metastatic pancreatic adenocarcinoma. While the Phase II objective is to assess the overall survival of patients with metastatic pancreatic adenocarcinoma treated with mFOLFIRINOX + PEGPH20 compared to those treated with mFOLFIRINOX alone. Assuming a 10% ineligibility rate, 7-20 study participants will be accrued to yield 6-18 eligible participants for the Phase I portion of the trial and 152 participants will be accrued to yield 138 eligible participants for the Phase II portion of the trial. The study will require 2 years of accrual, 1.5 years of follow-up, type 1 error of 10%, and 80% power. For the Phase II trial, study participants will be stratified according to Zubrod Performance Status: 0 vs. 1. The primary analysis of overall survival will be conducted in all eligible patients according to the intent-to-treat principle, using the logrank test. The final analysis will take place upon the observation of approximately 110 deaths. An interim analysis will be performed when one-third of the events (approximately 37 deaths) have been observed.

Phase

Phase 1/2 - for trials that are a combination of phases 1 and 2.

Inclusion and Exclusion 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

Sites

  • California

    • University of Southern California, Los Angeles, California, 90033
    • University of Southern California/Norris Cancer Center, Los Angeles, California, 90033
    • City of Hope, Duarte, California, 91010
    • City of Hope, Duarte, California, 91010
    • City of Hope, Duarte, California, 91010
  • Arizona

    • Arizona Cancer Center at University Medical Center North, Tucson, Arizona, 85719
    • Arizona Cancer Center at University Medical Center North, Tucson, Arizona, 85719
    • University of Arizona Health Sciences Center, Tucson, Arizona, 85724
  • Washington

    • University of Washington Medical Center, Seattle, Washington, 98195
    • University of Washington Medical Center, Seattle, Washington, 98195
Powered by SC CTSI