Untreated Metastatic Pancreatic Ductal Adenocarcinoma
Conditions
Brief summary
The purpose of this study is to find out if the study drugs nivolumab, albumin- bound paclitaxel, paricalcitol, cisplatin, and gemcitabine given together are safe and effective when combined to treat advanced pancreatic cancer.
Interventions
DRUGNivolumab
Nivolumab 240mg 240 mg as a 60 minute infusion on days 1, 15, 29 per 42 day cycle
DRUGAlbumin-bound paclitaxel
125 mg/m2 over 30 minutes IV infusion on days 1, 8 and 22, 29 per 42 day cycle
DRUGParicalcitol
25 micrograms IV on days 1,4,8,12,15,18,22,26,29,32,36,39 (+/-1 day allowed for dosing per 42 day cycle
DRUGCisplatin
25 mg/m2 over 60 minutes IV infusion on days 1, 8 and 22, 29 per 42 day cycle
DRUGGemcitabine
1000 mg/m2 over 30 minutes IV infusion on days 1, 8 and 22, 29 per 42 day cycle
Sponsors
Translational Genomics Research Institute
Bristol-Myers Squibb
Lustgarten Foundation
HonorHealth Research Institute
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
1. Age ≥18 years of age . 2. Histologically or cytologically confirmed metastatic pancreatic ductal adenocarcinoma. 3. Capable of providing informed consent and complying with Trial procedures. 4. Karnofsky Performance Status (KPS) of ≥ 70%. 5. Life expectancy ≥ 12 weeks. 6. Measurable tumor lesions according to RECIST 1.1 criteria. 7. Women must not be able to become pregnant (e.g. post-menopausal for at least 1 year, surgically sterile, or practicing adequate birth control methods) for the duration of the study. Women of child bearing potential must have a negative serum or urine pregnancy test at the Screening Visit and be non-lactating. Both male and female patients of reproductive potential must agree to use a reliable method of birth control during the study.
Exclusion criteria
1. Patients must have received no previous radiotherapy, surgery, chemotherapy or investigational therapy for the treatment of metastatic disease. Prior treatments in the adjuvant setting with gemcitabine and/or 5-FU (5-Fluorouracil) or gemcitabine administered as a radiation sensitizer are allowed, provided at least 6 months have elapsed since completion of the last dose and no lingering toxicities are present. 2. Palliative surgery and/or radiation treatment less than 4 weeks prior to initiation of study treatment. 3. Exposure to any investigational agent within 4 weeks prior to initiation of study treatment. 4. Evidence of central nervous system (CNS) metastasis (negative imaging study, if clinically indicated, within 4 weeks of Screening Visit). 5. History of other malignancies (except cured basal cell carcinoma, superficial bladder cancer or carcinoma in situ of the cervix) unless documented free of cancer for ≥5 years. 6. Laboratory values: Screening serum creatinine \> upper limit of normal (ULN); total bilirubin \> (ULN); alanine aminotransferase (ALT) and Aspartate transaminase (AST) ≥ 2.5 ULN or ≥ 5.0×ULN if liver metastases are present; absolute neutrophil count \<1,500/mm3, platelet concentration \<100,000/mm3, hematocrit level \<27% for females or \<30% for males, or coagulation tests (prothrombin time \[PT\], partial thromboplastin time \[PTT\], International Normalized Ratio \[INR\]) \>1.5×ULN unless on therapeutic doses of warfarin. 7. Current, serious, clinically significant cardiac arrhythmias as determined by the investigator. 8. History of HIV infection or active or chronic hepatitis B or C. 9. Active, clinically significant serious infection requiring treatment with antibiotics, anti-virals or anti-fungals. 10. Major surgery within 4 weeks prior to initiation of study treatment. 11. Any condition that might interfere with the patient's participation in the study or in the evaluation of the study results. 12. Any condition that is unstable and could jeopardize the patient's participation in the study. 13. Patient has a transplanted organ. 14. Patients with a history of autoimmune disease. 15. Prior Programmed cell death protein-1 (PD-1) or Programmed death-ligand-1 (PD-L1) therapy. 16. Patients taking any chemo or immunosuppressive steroids (equivalent to \> 20 mg hydrocortisone per day). 17. Patients cannot have \> Grade 1 pre-existing peripheral neuropathy (per CTCAE).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete Response Rate | From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 84 months | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete response (CR) rate as defined by CT scan using RECIST 1.1 criteria - disappearance of all target lesions and no new sites or disease-related symptoms confirmed at least 4 weeks after initial documentation and CA 19-9 (or CA 125, or CEA if not expressers of CA 19-9) down to normal limits; Partial Response (PR), at least a 30% decrease in the sum of the diameters of target lesions; Overall Response (OR) = CR + PR. When a complete response is documented, a Positron emission tomography (PET) scan will be obtained to confirm. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 84 months | Patients will be followed throughout their study participation and every 12 weeks following last dose of treatment until reported date of death. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Single Arm open label using combination therapy
Nivolumab: Nivolumab 240mg 240 mg as a 60 minute infusion on days 1, 15, 29 per 42 day cycle
Albumin-bound paclitaxel: 125 mg/m2 over 30 minutes IV infusion on days 1, 8 and 22, 29 per 42 day cycle
Paricalcitol: 25 micrograms IV on days 1,4,8,12,15,18,22,26,29,32,36,39 (+/-1 day allowed for dosing per 42 day cycle
Cisplatin: 25 mg/m2 over 60 minutes IV infusion on days 1, 8 and 22, 29 per 42 day cycle
Gemcitabine: 1000 mg/m2 over 30 minutes IV infusion on days 1, 8 and 22, 29 per 42 day cycle | 35 |
| Total | 35 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Achieved Best Response and converted to maintenance treatment off study | 12 |
| Overall Study | Adverse Event | 3 |
| Overall Study | Clinical Disease Progression | 5 |
| Overall Study | Progressive Disease by RECIST | 13 |
| Overall Study | Tolerability | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Single Arm |
|---|---|
| Age, Continuous | 63.0 years |
| Cancer Antigen (CA) 19-9 at C1/D1 Elevated (> 35) (U/mL) | 30 Participants |
| Cancer Antigen (CA) 19-9 at C1/D1 Normal (≤ 35) (U/mL) | 5 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 30 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| KARNOFSKY PERFORMANCE STATUS 100% | 7 Participants |
| KARNOFSKY PERFORMANCE STATUS 70% | 3 Participants |
| KARNOFSKY PERFORMANCE STATUS 80% | 7 Participants |
| KARNOFSKY PERFORMANCE STATUS 90% | 18 Participants |
| Primary Tumor Location pancreatic body | 9 participants |
| Primary Tumor Location pancreatic head | 13 participants |
| Primary Tumor Location pancreatic tail | 13 participants |
| Prior Treatment Prior chemotherapy | 4 participants |
| Prior Treatment Prior radiation | 2 participants |
| Prior Treatment Prior Surgery | 4 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 34 Participants |
| Region of Enrollment United States | 35 participants |
| Sex: Female, Male Female | 17 Participants |
| Sex: Female, Male Male | 18 Participants |
| Tumor Markers CA125 or CEA at C1/D1 Elevated CA125 and CA19-9 non-secreters | 3 Participants |
| Tumor Markers CA125 or CEA at C1/D1 Elevated CEA and CA19-9 non-secreters | 2 Participants |
| Vitamin D, ng/mL | 38.5 ng/mL |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 35 |
| other Total, other adverse events | 35 / 35 |
| serious Total, serious adverse events | 14 / 35 |
Outcome results
Primary
Complete Response Rate
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete response (CR) rate as defined by CT scan using RECIST 1.1 criteria - disappearance of all target lesions and no new sites or disease-related symptoms confirmed at least 4 weeks after initial documentation and CA 19-9 (or CA 125, or CEA if not expressers of CA 19-9) down to normal limits; Partial Response (PR), at least a 30% decrease in the sum of the diameters of target lesions; Overall Response (OR) = CR + PR. When a complete response is documented, a Positron emission tomography (PET) scan will be obtained to confirm.
Time frame: From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 84 months
Population: Not evaluable for overall response as subject did not have post baseline scans (n=3)
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Single Arm | Complete Response Rate | Overall Response Rate (CR + PR) | 21 Participants |
| Single Arm | Complete Response Rate | Stable Disease (SD) | 9 Participants |
| Single Arm | Complete Response Rate | Progressive Disease (PD) | 2 Participants |
Secondary
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0
Patients will be followed throughout their study participation and every 12 weeks following last dose of treatment until reported date of death.
Time frame: From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 84 months
Population: adverse events (grade ≥ 3) observed in the study related to study treatment
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Single Arm | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | peripheral sensory neuropathy | 4 Participants |
| Single Arm | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | thrombocytopenia | 22 Participants |
| Single Arm | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | anemia | 13 Participants |
| Single Arm | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | white blood cell decreased | 5 Participants |
| Single Arm | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | neutropenia | 4 Participants |
| Single Arm | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | colitis | 3 Participants |
| Single Arm | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | diarrhea | 3 Participants |
| Single Arm | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | hypokalemia | 3 Participants |
| Single Arm | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | unspecified rash | 3 Participants |