The purpose of this trial is to evaluate the effect of investigational drug nivolumab in
combination with either gemcitabine/cisplatin chemotherapy, or in combination with another
investigational agent ipilimumab in patients with advanced unresectable biliary tract
Gemcitabine/cisplatin is the standard of care treatment for biliary tract cancer.
Nivolumab and ipilimumab are types of immunotherapy. Immunotherapy works by encouraging the
body's own immune system to attack the cancer cells. Nivolumab (Opdivo) is FDA approved for
the treatment of several cancers including metastatic melanoma, advanced lung, kidney, head
& neck and bladder cancer. The combination of nivolumab and ipilimumab (Yervoy) is FDA
approved for metastatic melanoma.
- Patients must have a pathologically confirmed adenocarcinoma of the biliary tract
(intra-hepatic, extra-hepatic (hilar, distal) or gall bladder) that is not eligible
for curative resection, transplantation, or ablative therapies.
- Patients may have received prior radiation, chemoembolization, radioembolization or
other local ablative therapies or hepatic resection if completed ≥ 4 weeks prior to
registration AND if patient has recovered to <= grade 1 toxicity.
- Patients must have radiographically measurable disease in at least one site not
previously treated with radiation or liver directed therapy (including bland, chemo-
or radio-embolization, or ablation) either within the liver or in a metastatic site.
- Age≥18 years
- Child-Pugh score of A (prognosis in chronic liver disease and cirrhosis)
- ECOG (Eastern Cooperative Oncology Group) performance status of 0-1
- Ability to understand and willingness to sign IRB-approved informed consent
- Willing to provide archived tissue, if available, from a previous diagnostic biopsy
- Must be able to tolerate CT (computerized tomography) and/or MRI (magnetic resonance
imaging) with contrast
- Adequate organ function obtained ≤ 2 weeks prior to registration
- Patients may not have received prior systemic treatment (chemotherapy or targeted
therapy) for advanced BTC (biliary tract cancer). Prior adjuvant chemotherapy is
permitted provided it was completed > 6 months from registration.
- Must not have a diagnosis of immunodeficiency, or receiving systemic steroid therapy,
or any other form of immunosuppressive therapy within 7 days prior to trial
- No known Hepatitis B, Hepatitis C, or HIV seropositivity. Testing is not required in
absence of clinical suspicion.
- No prior history of organ transplantation or brain metastasis.
- Must not have undergone a major surgical procedure < 4 weeks prior to registration.
- Must not have an active second malignancy other than non-melanoma skin cancer or
cervical carcinoma in situ. Patients with history of malignancy are eligible provided
primary treatment of that cancer was completed > 1 year prior to registration and the
patient is free of clinical or radiologic evidence of recurrent or progressive
- Must have no ongoing active, uncontrolled infections
- Must not have received a live vaccine within 30 days of planned start of the study
- Must not have a psychiatric illness, other significant medical illness, or social
situation which, in the investigator's opinion, would limit compliance or ability to
comply with study requirements.
- Women must not be pregnant or breastfeeding since nab-paclitaxel and/or gemcitabine
may harm the fetus or child.
- Women of child-bearing potential and men must agree to use 2 methods of adequate
contraception (hormonal plus barrier or 2 barrier forms) OR abstinence prior to study
entry, for the duration of study participation and for 5 months (for women) and 7
months (for men) following completion of study therapy.
- Participants with an active, known or suspected autoimmune disease. Participants with
type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin
disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic
treatment, or conditions not expected to recur in the absence of an external trigger
are permitted to enroll.
- Participants with a condition requiring systemic treatment with either
corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive
medications within 14 days of start of study treatment. Inhaled or topical steroids,
and adrenal replacement steroid doses > 10 mg daily prednisone equivalent, are
permitted in the absence of active autoimmune disease.