Metastatic Pancreatic Adenocarcinoma
Conditions
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.
Detailed 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.
Interventions
DRUGPEGPH20
3 ug/kg on Day 1, IV over 15 minutes
DRUGOxaliplatin
85 mg/m\^2, on Day 2, IV over 2 hours
DRUGLeucovorin
400 mg/m\^2, on Day 2, IV over 2 hours
DRUGIrinotecan
180 mg/m\^2, on Day 2, IV over 1.5 hours
DRUG5-fluorouracil
2,400 mg/m\^2, Days 2-4, IV over 46 hours
Sponsors
National Cancer Institute (NCI)
Halozyme Therapeutics
SWOG Cancer Research Network
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase I: Maximum Tolerated Dose (MTD) of PEGPH20 in Combination With mFOLFIRINOX | 2 cycles of 14 days | 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. |
| Phase II: Overall Survival | From date of registration to date of death due to any cause, assessed up to 3 years | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Tumor Response Rate (Confirmed and Unconfirmed, Complete and Partial) | Up to 3 years | 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 |
| Progression Free Survival (PFS) (Phase II) | From date of registration to date of death due to any cause, assessed up to 3 years | 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. |
| Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Duration of treatment and follow up until death or 3 years post registration | 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 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Plasma Expression of Hyaluronan (HA) | Within 2 years of end of study | — |
| Tumor Expression of HA | Within 2 years of end of study | — |
| Cancer Antigen (CA) 19-9 Levels | 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. |
Countries
United States
Participant flow
Pre-assignment details
126 participants were enrolled to this study, however, 1 withdrew consent and 3 were ineligible.
Participants by arm
| Arm | Count |
|---|---|
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 and Day 3/4 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 | 5 |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 Only 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 | 6 |
| 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.
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 | 56 |
| 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.
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 | 55 |
| Total | 122 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Phase II | Adverse Event | 0 | 0 | 10 | 11 |
| Phase II | Death | 0 | 0 | 3 | 1 |
| Phase II | Disease progression | 0 | 0 | 26 | 34 |
| Phase II | On treatment | 0 | 0 | 4 | 0 |
| Phase II | Other/Unknown | 0 | 0 | 8 | 5 |
| Phase II | Patient Refusal | 0 | 0 | 5 | 4 |
Baseline characteristics
| Characteristic | Total | Phase II: mFOLFIRINOX + PEGPH20 | Phase II: mFOLFIRINOX | Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 Only | Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 and Day 3/4 |
|---|---|---|---|---|---|
| Age, Continuous | 62.2 years | 63.9 years | 60.5 years | 60.2 years | 65.4 years |
| Primary site Body of pancreas | 33 Participants | 16 Participants | 16 Participants | 0 Participants | 1 Participants |
| Primary site Head of pancreas | 41 Participants | 19 Participants | 16 Participants | 4 Participants | 2 Participants |
| Primary site Pancreas, NOS | 19 Participants | 9 Participants | 9 Participants | 1 Participants | 0 Participants |
| Primary site Tail of pancreas | 29 Participants | 11 Participants | 15 Participants | 1 Participants | 2 Participants |
| Prior treatment for pancreatic cancer Chemotherapy | 8 Participants | 4 Participants | 3 Participants | 1 Participants | 0 Participants |
| Prior treatment for pancreatic cancer Surgery | 10 Participants | 7 Participants | 2 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 12 Participants | 7 Participants | 4 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 1 Participants | 4 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 7 Participants | 4 Participants | 2 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 96 Participants | 43 Participants | 46 Participants | 4 Participants | 3 Participants |
| Serum cancer antigen (CA) 19-9 < 37 | 19 Participants | 7 Participants | 10 Participants | 1 Participants | 1 Participants |
| Serum cancer antigen (CA) 19-9 >= 37 | 103 Participants | 48 Participants | 46 Participants | 5 Participants | 4 Participants |
| Sex: Female, Male Female | 61 Participants | 31 Participants | 25 Participants | 2 Participants | 3 Participants |
| Sex: Female, Male Male | 61 Participants | 24 Participants | 31 Participants | 4 Participants | 2 Participants |
| Sites of involvement Distant lymph nodes | 14 Participants | 5 Participants | 6 Participants | 3 Participants | 0 Participants |
| Sites of involvement Liver | 94 Participants | 42 Participants | 45 Participants | 3 Participants | 4 Participants |
| Sites of involvement Lung | 34 Participants | 14 Participants | 18 Participants | 1 Participants | 1 Participants |
| Sites of involvement Other | 23 Participants | 9 Participants | 12 Participants | 1 Participants | 1 Participants |
| Sites of involvement Peritoneum | 25 Participants | 11 Participants | 12 Participants | 1 Participants | 1 Participants |
| Sites of involvement Primary tumor/pancreas | 108 Participants | 49 Participants | 51 Participants | 4 Participants | 4 Participants |
| Sites of involvement Regional lymph nodes | 44 Participants | 16 Participants | 22 Participants | 3 Participants | 3 Participants |
| Zubrod performance status 0 | 70 Participants | 32 Participants | 31 Participants | 5 Participants | 2 Participants |
| Zubrod performance status 1 | 52 Participants | 23 Participants | 25 Participants | 1 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 5 / 5 | 5 / 6 | 49 / 56 | 50 / 55 |
| other Total, other adverse events | 4 / 5 | 6 / 6 | 52 / 54 | 50 / 51 |
| serious Total, serious adverse events | 3 / 5 | 4 / 6 | 9 / 54 | 36 / 51 |
Outcome results
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.
Time frame: From date of registration to date of death due to any cause, assessed up to 3 years
Population: Eligible and analyzable participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 and Day 3/4 | Phase II: Overall Survival | 14.4 months |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 | Phase II: Overall Survival | 7.7 months |
p-value: <0.0195% CI: [1.28, 3.34]Regression, Cox
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.
Time frame: 2 cycles of 14 days
Population: All analyzable patients who experienced a dose limiting toxicity attributable to PEGPH20 and/or mFOLFIRINOX in the first cycle
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 and Day 3/4 | Phase I: Maximum Tolerated Dose (MTD) of PEGPH20 in Combination With mFOLFIRINOX | 0 ug/kg |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 | Phase I: Maximum Tolerated Dose (MTD) of PEGPH20 in Combination With mFOLFIRINOX | 3 ug/kg |
| All Phase 1 Participants | Phase I: Maximum Tolerated Dose (MTD) of PEGPH20 in Combination With mFOLFIRINOX | 3 ug/kg |
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
Time frame: Duration of treatment and follow up until death or 3 years post registration
Population: Patients who received at least one dose of protocol treatment. Only 105 participants in the phase II trial were assessed for AEs, as 6 participants did not receive protocol treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 and Day 3/4 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Diarrhea | 1 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 and Day 3/4 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Weight loss | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 and Day 3/4 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Infections and infestations - Other, specify | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 and Day 3/4 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypotension | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 and Day 3/4 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Esophagitis | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 and Day 3/4 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Small intestine infection | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 and Day 3/4 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypophosphatemia | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 and Day 3/4 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hyponatremia | 1 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 and Day 3/4 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Fatigue | 2 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 and Day 3/4 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Skin infection | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 and Day 3/4 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypokalemia | 1 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 and Day 3/4 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypertension | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 and Day 3/4 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Febrile neutropenia | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 and Day 3/4 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Anemia | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 and Day 3/4 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hyperglycemia | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 and Day 3/4 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Generalized muscle weakness | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 and Day 3/4 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Gallbladder obstruction | 1 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 and Day 3/4 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Acute kidney injury | 1 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 and Day 3/4 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | General disorders and admin site conditions- Other | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 and Day 3/4 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Gastrointestinal disorders - Other, specify | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 and Day 3/4 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Sepsis | 1 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 and Day 3/4 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Resp, thoracic and mediastinal disorders - Other | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 and Day 3/4 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Anorexia | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 and Day 3/4 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Abdominal pain | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 and Day 3/4 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pulmonary hypertension | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 and Day 3/4 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Portal vein thrombosis | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 and Day 3/4 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Arthralgia | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 and Day 3/4 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Vomiting | 1 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 and Day 3/4 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Platelet count decreased | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 and Day 3/4 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Myalgia | 1 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 and Day 3/4 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Ascites | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 and Day 3/4 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Ventricular tachycardia | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 and Day 3/4 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Peritoneal infection | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 and Day 3/4 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Peripheral sensory neuropathy | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 and Day 3/4 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Aspartate aminotransferase increased | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 and Day 3/4 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Alanine aminotransferase increased | 1 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 and Day 3/4 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Peripheral motor neuropathy | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 and Day 3/4 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Paresthesia | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 and Day 3/4 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Blood bilirubin increased | 1 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 and Day 3/4 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | White blood cell decreased | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 and Day 3/4 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pain | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 and Day 3/4 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Neutrophil count decreased | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 and Day 3/4 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Creatinine increased | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 and Day 3/4 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Thromboembolic event | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 and Day 3/4 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Nausea | 1 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 and Day 3/4 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Mucositis oral | 1 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 and Day 3/4 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Dehydration | 1 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 and Day 3/4 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Spasticity | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 and Day 3/4 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Lymphocyte count decreased | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 and Day 3/4 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Lung infection | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 and Day 3/4 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Depression | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 and Day 3/4 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Alkaline phosphatase increased | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 and Day 3/4 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Leukocytosis | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 and Day 3/4 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Infusion related reaction | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Peritoneal infection | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Myalgia | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Abdominal pain | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Acute kidney injury | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Alanine aminotransferase increased | 1 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Alkaline phosphatase increased | 1 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Anemia | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Anorexia | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Arthralgia | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Ascites | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Aspartate aminotransferase increased | 1 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Blood bilirubin increased | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Creatinine increased | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Dehydration | 1 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Depression | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Diarrhea | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Esophagitis | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Fatigue | 1 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Febrile neutropenia | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Gallbladder obstruction | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Gastrointestinal disorders - Other, specify | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | General disorders and admin site conditions- Other | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Generalized muscle weakness | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hyperglycemia | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypertension | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypokalemia | 1 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hyponatremia | 1 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypophosphatemia | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypotension | 1 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Infections and infestations - Other, specify | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Infusion related reaction | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Leukocytosis | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Lung infection | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Lymphocyte count decreased | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Mucositis oral | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Nausea | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Neutrophil count decreased | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pain | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Paresthesia | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Peripheral motor neuropathy | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Peripheral sensory neuropathy | 2 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Platelet count decreased | 1 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Portal vein thrombosis | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pulmonary hypertension | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Resp, thoracic and mediastinal disorders - Other | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Sepsis | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Skin infection | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Small intestine infection | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Spasticity | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Thromboembolic event | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Ventricular tachycardia | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Vomiting | 1 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Weight loss | 0 Participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | White blood cell decreased | 0 Participants |
| All Phase 1 Participants | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypotension | 0 Participants |
| All Phase 1 Participants | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Diarrhea | 10 Participants |
| All Phase 1 Participants | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Infections and infestations - Other, specify | 1 Participants |
| All Phase 1 Participants | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Infusion related reaction | 0 Participants |
| All Phase 1 Participants | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Depression | 1 Participants |
| All Phase 1 Participants | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Weight loss | 1 Participants |
| All Phase 1 Participants | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Leukocytosis | 2 Participants |
| All Phase 1 Participants | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Spasticity | 0 Participants |
| All Phase 1 Participants | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Lung infection | 1 Participants |
| All Phase 1 Participants | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Dehydration | 7 Participants |
| All Phase 1 Participants | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Lymphocyte count decreased | 1 Participants |
| All Phase 1 Participants | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Alanine aminotransferase increased | 0 Participants |
| All Phase 1 Participants | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Mucositis oral | 0 Participants |
| All Phase 1 Participants | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Myalgia | 0 Participants |
| All Phase 1 Participants | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Creatinine increased | 1 Participants |
| All Phase 1 Participants | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Nausea | 8 Participants |
| All Phase 1 Participants | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Thromboembolic event | 1 Participants |
| All Phase 1 Participants | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Neutrophil count decreased | 4 Participants |
| All Phase 1 Participants | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Blood bilirubin increased | 0 Participants |
| All Phase 1 Participants | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pain | 1 Participants |
| All Phase 1 Participants | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Paresthesia | 1 Participants |
| All Phase 1 Participants | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Aspartate aminotransferase increased | 0 Participants |
| All Phase 1 Participants | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Abdominal pain | 1 Participants |
| All Phase 1 Participants | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Peripheral motor neuropathy | 1 Participants |
| All Phase 1 Participants | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Ventricular tachycardia | 1 Participants |
| All Phase 1 Participants | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Peripheral sensory neuropathy | 2 Participants |
| All Phase 1 Participants | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Ascites | 0 Participants |
| All Phase 1 Participants | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Peritoneal infection | 0 Participants |
| All Phase 1 Participants | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Arthralgia | 0 Participants |
| All Phase 1 Participants | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Platelet count decreased | 2 Participants |
| All Phase 1 Participants | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Acute kidney injury | 0 Participants |
| All Phase 1 Participants | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Portal vein thrombosis | 0 Participants |
| All Phase 1 Participants | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Anorexia | 2 Participants |
| All Phase 1 Participants | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pulmonary hypertension | 1 Participants |
| All Phase 1 Participants | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Vomiting | 8 Participants |
| All Phase 1 Participants | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Resp, thoracic and mediastinal disorders - Other | 1 Participants |
| All Phase 1 Participants | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Anemia | 4 Participants |
| All Phase 1 Participants | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Sepsis | 1 Participants |
| All Phase 1 Participants | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Gastrointestinal disorders - Other, specify | 0 Participants |
| All Phase 1 Participants | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Gallbladder obstruction | 0 Participants |
| All Phase 1 Participants | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | General disorders and admin site conditions- Other | 1 Participants |
| All Phase 1 Participants | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Generalized muscle weakness | 1 Participants |
| All Phase 1 Participants | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Febrile neutropenia | 1 Participants |
| All Phase 1 Participants | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hyperglycemia | 1 Participants |
| All Phase 1 Participants | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Skin infection | 0 Participants |
| All Phase 1 Participants | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypertension | 1 Participants |
| All Phase 1 Participants | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Fatigue | 6 Participants |
| All Phase 1 Participants | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypokalemia | 3 Participants |
| All Phase 1 Participants | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Alkaline phosphatase increased | 0 Participants |
| All Phase 1 Participants | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hyponatremia | 1 Participants |
| All Phase 1 Participants | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Esophagitis | 0 Participants |
| All Phase 1 Participants | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | White blood cell decreased | 2 Participants |
| All Phase 1 Participants | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypophosphatemia | 0 Participants |
| All Phase 1 Participants | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Small intestine infection | 0 Participants |
| Phase II: PEGPH20 + mFOLFIRINOX | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | General disorders and admin site conditions- Other | 0 Participants |
| Phase II: PEGPH20 + mFOLFIRINOX | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypotension | 0 Participants |
| Phase II: PEGPH20 + mFOLFIRINOX | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Peritoneal infection | 1 Participants |
| Phase II: PEGPH20 + mFOLFIRINOX | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Small intestine infection | 1 Participants |
| Phase II: PEGPH20 + mFOLFIRINOX | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Febrile neutropenia | 0 Participants |
| Phase II: PEGPH20 + mFOLFIRINOX | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Infections and infestations - Other, specify | 0 Participants |
| Phase II: PEGPH20 + mFOLFIRINOX | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Depression | 0 Participants |
| Phase II: PEGPH20 + mFOLFIRINOX | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Alanine aminotransferase increased | 3 Participants |
| Phase II: PEGPH20 + mFOLFIRINOX | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Ventricular tachycardia | 0 Participants |
| Phase II: PEGPH20 + mFOLFIRINOX | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Infusion related reaction | 1 Participants |
| Phase II: PEGPH20 + mFOLFIRINOX | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Alkaline phosphatase increased | 2 Participants |
| Phase II: PEGPH20 + mFOLFIRINOX | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Platelet count decreased | 3 Participants |
| Phase II: PEGPH20 + mFOLFIRINOX | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Anorexia | 3 Participants |
| Phase II: PEGPH20 + mFOLFIRINOX | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Leukocytosis | 1 Participants |
| Phase II: PEGPH20 + mFOLFIRINOX | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Dehydration | 4 Participants |
| Phase II: PEGPH20 + mFOLFIRINOX | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Skin infection | 1 Participants |
| Phase II: PEGPH20 + mFOLFIRINOX | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Generalized muscle weakness | 3 Participants |
| Phase II: PEGPH20 + mFOLFIRINOX | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Lung infection | 0 Participants |
| Phase II: PEGPH20 + mFOLFIRINOX | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Portal vein thrombosis | 1 Participants |
| Phase II: PEGPH20 + mFOLFIRINOX | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Spasticity | 1 Participants |
| Phase II: PEGPH20 + mFOLFIRINOX | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hyponatremia | 3 Participants |
| Phase II: PEGPH20 + mFOLFIRINOX | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Lymphocyte count decreased | 4 Participants |
| Phase II: PEGPH20 + mFOLFIRINOX | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Creatinine increased | 0 Participants |
| Phase II: PEGPH20 + mFOLFIRINOX | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | White blood cell decreased | 2 Participants |
| Phase II: PEGPH20 + mFOLFIRINOX | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Abdominal pain | 3 Participants |
| Phase II: PEGPH20 + mFOLFIRINOX | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Mucositis oral | 4 Participants |
| Phase II: PEGPH20 + mFOLFIRINOX | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pulmonary hypertension | 0 Participants |
| Phase II: PEGPH20 + mFOLFIRINOX | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Myalgia | 2 Participants |
| Phase II: PEGPH20 + mFOLFIRINOX | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Anemia | 2 Participants |
| Phase II: PEGPH20 + mFOLFIRINOX | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Weight loss | 0 Participants |
| Phase II: PEGPH20 + mFOLFIRINOX | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypokalemia | 4 Participants |
| Phase II: PEGPH20 + mFOLFIRINOX | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Nausea | 12 Participants |
| Phase II: PEGPH20 + mFOLFIRINOX | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Blood bilirubin increased | 1 Participants |
| Phase II: PEGPH20 + mFOLFIRINOX | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hyperglycemia | 1 Participants |
| Phase II: PEGPH20 + mFOLFIRINOX | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Resp, thoracic and mediastinal disorders - Other | 0 Participants |
| Phase II: PEGPH20 + mFOLFIRINOX | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Neutrophil count decreased | 3 Participants |
| Phase II: PEGPH20 + mFOLFIRINOX | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Fatigue | 11 Participants |
| Phase II: PEGPH20 + mFOLFIRINOX | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Thromboembolic event | 5 Participants |
| Phase II: PEGPH20 + mFOLFIRINOX | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Vomiting | 10 Participants |
| Phase II: PEGPH20 + mFOLFIRINOX | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pain | 0 Participants |
| Phase II: PEGPH20 + mFOLFIRINOX | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Aspartate aminotransferase increased | 0 Participants |
| Phase II: PEGPH20 + mFOLFIRINOX | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Acute kidney injury | 0 Participants |
| Phase II: PEGPH20 + mFOLFIRINOX | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Gallbladder obstruction | 0 Participants |
| Phase II: PEGPH20 + mFOLFIRINOX | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Paresthesia | 0 Participants |
| Phase II: PEGPH20 + mFOLFIRINOX | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Esophagitis | 1 Participants |
| Phase II: PEGPH20 + mFOLFIRINOX | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Diarrhea | 12 Participants |
| Phase II: PEGPH20 + mFOLFIRINOX | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Gastrointestinal disorders - Other, specify | 1 Participants |
| Phase II: PEGPH20 + mFOLFIRINOX | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Peripheral motor neuropathy | 1 Participants |
| Phase II: PEGPH20 + mFOLFIRINOX | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Ascites | 1 Participants |
| Phase II: PEGPH20 + mFOLFIRINOX | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypertension | 0 Participants |
| Phase II: PEGPH20 + mFOLFIRINOX | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Sepsis | 1 Participants |
| Phase II: PEGPH20 + mFOLFIRINOX | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Peripheral sensory neuropathy | 5 Participants |
| Phase II: PEGPH20 + mFOLFIRINOX | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypophosphatemia | 1 Participants |
| Phase II: PEGPH20 + mFOLFIRINOX | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Arthralgia | 1 Participants |
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
Time frame: Up to 3 years
Population: Participants with measurable disease
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 and Day 3/4 | Objective Tumor Response Rate (Confirmed and Unconfirmed, Complete and Partial) | 45 percent of participants |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 | Objective Tumor Response Rate (Confirmed and Unconfirmed, Complete and Partial) | 33 percent of participants |
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.
Time frame: From date of registration to date of death due to any cause, assessed up to 3 years
Population: Eligible and analyzable participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 and Day 3/4 | Progression Free Survival (PFS) (Phase II) | 6.2 months |
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 | Progression Free Survival (PFS) (Phase II) | 4.3 months |
p-value: 0.0195% CI: [1.14, 2.66]Regression, Cox
Other Pre-specified
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.
Time frame: Within 2 years of the end of the study
Other Pre-specified
Plasma Expression of Hyaluronan (HA)
Time frame: Within 2 years of end of study
Other Pre-specified
Tumor Expression of HA
Time frame: Within 2 years of end of study