| Eligibility |
Inclusion Criteria:
- Signed informed consent
- Subjects must have signed and dated an IRB/IEC approved written informed consent
form in accordance with regulatory and institutional guidelines. This must be
obtained before the performance of any protocol related procedures that are not
part of normal subject care
- Subjects must be willing and able to comply with scheduled visits, treatment
schedule, laboratory testing, and other requirements of the study
- Histological or cytological confirmation of advanced pancreatic carcinoma prior to
entering this study
- Prior therapy requirements:
- There is no upper limit on the number of prior chemotherapy regimens received.
Participants must have received and progressed during or after at least 1 line of
systemic chemotherapy in the metastatic setting (gemcitabine or 5-FU based
regimens).
- Notes:
- If a participant received adjuvant/neoadjuvant systemic combinational
therapy, and progressed within 6 months, the adjuvant/neoadjuvant treatment
will be considered as 1 line of systemic treatment.
- In general, discontinuation of 1 drug in a multi-drug regimen and
continuation of other drug(s), is considered part of the same line of
treatment. Restarting the same regimen after a drug holiday or maintenance
chemotherapy can also be considered part of the same line of treatment.
Switching from IV (5-FU) to an oral formulation (capecitabine) of the same
drug is also considered part of the same line of treatment
- Minimum time from first systemic therapy for recurrent/metastatic
adenocarcinoma of pancreas to progression should be at least 3 months
- Age 18 years and older
- ECOG Performance Status (PS) 0-1
- All participants will be required to undergo mandatory pre- and on-treatment biopsies
at acceptable clinical risk as judged by the investigator. An archival pre-treatment
sample is not acceptable.
- Participants must have normal organ and marrow function as defined below:
- Absolute neutrophil count (ANC) = 1.5 x 10?/L
- Platelet count = 75 x 10?/L
- Serum bilirubin = 1.5 x upper limit of normal (ULN)
- AST/ALT = 5 x ULN
- Serum creatinine = 1.5 x ULN or CrCl = 40 mL/min (using the Cockcroft-Gault
formula)
- Women of childbearing potential (WOCBP) must use method(s) of contraception as
indicated in Appendix 3. For a teratogenic study drug and/or when there is
insufficient information to assess teratogenicity (preclinical studies have not been
done), a highly effective method(s) of contraception (failure rate of less than 1% per
year) is required. The individual methods of contraception and duration should be
determined in consultation with the investigator. WOCBP must follow instructions for
birth control when the half-life of the investigational drug is greater than 24 hours,
contraception should be continued for a period of 30 days plus the time required for
the investigational drug to undergo five half-lives. The half-life of nivolumab and
ipilimumab is up to 25 days and 18 days, respectively. WOCBP should therefore use an
adequate method to avoid pregnancy during the treatment and for 23 weeks (30 days plus
the time required for nivolumab to undergo five half-lives) after the last dose of
investigational drug
- Men who are sexually active with WOCBP must use any contraceptive method with a
failure rate of less than 1% per year. The investigator shall review contraception
methods and the time period that contraception must be followed. Men that are sexually
active with WOCBP must follow instructions for birth control when the half-life of the
investigational drug is greater than 24 hours, contraception should be continued for a
period of 90 days plus thetime required for the investigational drug to undergo five
half-lives. The half-life of nivolumab is up to 25 days. Men who are sexually active
with WOCBP must continue contraception during the treatment and for 31 weeks (90 days
plus the time required for nivolumab to undergo five half-lives) after the last dose
of investigational drug. Women who are not of childbearing potential (i.e. who are
postmenopausal or surgically sterile as well as azoospermic men do not require
contraception
- Subjects must have signed and dated a BIOPAC approved written informed consent form in
accordance with regulatory and institutional guidelines.
Exclusion Criteria:
- Any serious or uncontrolled medical disorder that, in the opinion of the investigator,
may increase the risk associated with study participation or study drug
administration, impair the ability of the subject to receive protocol therapy, or
interfere with the interpretation of study results
- Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4
antibody, or any other antibody or drug specifically targeting T-cell co-stimulation
or checkpoint pathways
- Participants with active, known or suspected autoimmune disease. Participants are
permitted to enroll with vitiligo, type I diabetes mellitus, residual hypothyroidism
due to autoimmune condition only requiring hormone replacement, psoriasis not
requiring systemic treatment, or conditions not expected to recur in the absence of an
external trigger.
- Current or prior use of immunosuppressive medication within 14 days before the first
dose of nivolumab, ipilimumab and radiation in combination with TGFß-15 peptide
vaccine. The following are exceptions to this criterion:
- Intranasal, inhaled, or topical steroids; or local steroid injections (e.g.
intra-articular injection)
- Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of
prednisone or equivalent
- Steroids as premedication for hypersensitivity reactions (e.g. CT scan
premedication)
- Participants should be excluded if they have known history of testing positive for
human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
- Allergies and Adverse Drug Reaction
- History of allergy to study drug components
- History of severe hypersensitivity reaction to any monoclonal antibody
- WOCBP who are pregnant or breastfeeding
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