Metastatic Pancreatic Adenocarcinoma, Stage IV Pancreatic Cancer AJCC v8
Conditions
Brief summary
This phase II trial studies how well pembrolizumab and PEGPH20 work in treating patients with pancreatic cancer that has spread to other places in the body (metastatic). Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. PEGPH20 is an enzyme that breaks down hyaluronic acid coating tumor cells which may inhibit growth of tumor cells. Giving pembrolizumab and PEGPH20 may work better in treating patients with pancreatic cancer compared to pembrolizumab alone.
Detailed description
PRIMARY OBJECTIVES: I. To assess the progression free survival duration of patients treated with the combination of pegylated recombinant human hyaluronidase PH20 (PEGPH20) and pembrolizumab. SECONDARY OBJECTIVES: I. To assess the safety and tolerability of the combination of PEGPH20 and pembrolizumab. EXPLORATORY OBJECTIVES: I. To evaluate objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) and Immune-Modified Response Evaluation Criteria in Solid Tumors (iRECIST) criteria, duration of response (DOR), disease control rate (DCR), time to progression (TTP) and progression-free survival (PFS) per RECIST and iRECIST as assessed by M.D. Anderson investigators and overall survival (OS) of the combination of pembrolizumab and PEGPH20. II. To explore the association between PD-L1 expression by immunohistochemistry (IHC), shed PD-L1 level, hyaluronan (HA) levels, somatic gene expression profiling and antitumor efficacy of the combination of pembrolizumab and PEGPH20 based on RECIST 1.1 as well as OS. III. To explore the relationship between genomic variation and response to study treatment. IV. To examine the effect of pembrolizumab and PEGPH20 on immune cell infiltration into tumor. V. To explore the effect of PEGPH20 on serum HA levels, and to compare changes in serum HA with clinical efficacy. VI. To determine the impact of the combination of pembrolizumab and PEGPH20 on circulating immune cells. OUTLINE: Patients receive pembrolizumab intravenously (IV) over 10 minutes on day 1 and pegylated recombinant human hyaluronidase PH20 subcutaneously (SC) on days 1, 8, and 15. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days and then every 9 and 12 weeks.
Interventions
Given SC
BIOLOGICALPembrolizumab
Given IV
Sponsors
National Cancer Institute (NCI)
M.D. Anderson Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have histologically or cytologically confirmed diagnosis of pancreatic adenocarcinoma based on pathology report * Be willing and able to provide written informed consent for the trial. The subject may also provide consent for Future Biomedical Research. However, the subject may participate in the main trial without participating in Future Biomedical Research. * Have at least one measurable lesion and one lesion available for biopsy (not the primary pancreatic lesion) based on RECIST 1.1. Target lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions * Have had prior treatment with first-line therapy for metastatic disease for at least 4 months, and have had a radiologic response or stable disease at the most recent imaging. Adjuvant therapy for resected disease will not count as first-line therapy. Therapies that are derivative of others (e.g. fluorouracil/leucovorin calcium/oxaliplatin \[FOLFOX\] vis-a-vis fuorouracil/irinotecan/leucovorin/oxaliplatin \[FOLFIRINOX\]) will be counted as a single line of treatment for the purpose of determining the number of prior therapies * Be willing to undergo a core biopsy or excisional biopsy of tumor from a metastatic site. Note that the biopsy itself will be done only after the patient has been found to meet all other inclusion/
Exclusion criteria
and the patient is otherwise prepared to start therapy * Be willing to provide (and have available) archival tissue from a surgical or biopsy specimen obtained PRIOR to the most recent chemotherapy * Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale * Demonstrate adequate organ function. Specimens must be collected within 10 days prior to the start of trial treatment * Female subjects of childbearing potential must have a negative urine or serum pregnancy test at screening (prior to biopsy) and again within 24 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required * Male and female subjects of childbearing potential must agree to use an adequate method of contraception starting with the first dose of trial therapy through 120 days after the last dose of trial therapy. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject. Acceptable methods of contraception are as follows: * Single method (1 of the following is acceptable): intrauterine device (IUD), vasectomy of a female subject's male partner, contraceptive rod implanted into the skin * Combination method (requires use of 2 of the following): diaphragm with spermicide (cannot be used in conjunction with cervical cap/spermicide), cervical cap with spermicide (nulliparous women only), contraceptive sponge (nulliparous women only), male condom or female condom (cannot be used together), hormonal contraceptive: oral contraceptive pill (estrogen/ progestin pill or progestin-only pill), contraceptive skin patch, vaginal contraceptive ring, or subcutaneous (SC) contraceptive injection
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression free survival (PFS) | Up to 1 year | Descriptive statistics including with 90% confidence interval will be computed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of adverse events | Up to 30 days post treatment | Descriptive statistics including with 90% confidence interval will be computed. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Disease control rate (DCR) | Up to 1 year | DCR will be evaluated per RECIST and iRECIST. Descriptive statistics including with 90% confidence interval will be computed. |
| Time to progression (TTP) | Up to 1 year | TTP will be evaluated per RECIST and iRECIST. Descriptive statistics including with 90% confidence interval will be computed. |
| Objective response rate (ORR) | Up to 1 year | ORR will be evaluated per Response Evaluation Criteria in Solid Tumors (RECIST) and Immune-Modified Response Evaluation Criteria in Solid Tumors (iRECIST) criteria. Descriptive statistics including with 90% confidence interval will be computed. |
| Overall survival | Up to 1 year | Descriptive statistics including with 90% confidence interval will be computed. |
| PFS | Up to 1 year | PFS will be evaluated per RECIST and iRECIST. Descriptive statistics including with 90% confidence interval will be computed. |
| Duration of response (DOR) | Up to 1 year | DOR will be evaluated per RECIST and iRECIST. Descriptive statistics including with 90% confidence interval will be computed. |
Countries
United States
Outcome results
None listed