A Phase 1b and Pharmacodynamic Study of Nintedanib Monotherapy Followed by Combination Therapy of Nintedanib and Gemcitabine Plus nab-Paclitaxel for Advanced Pancreatic Cancer
- Zale Lipshy University Hospital
Muhammad Beg, M.D.
This a open-label, single arm, multi-center, phase 1b study of the pharmacodynamics of nintedanib as a monotherapy followed by a combination therapy of nintedanib and gemcitabine plus nab-paclitaxel for advanced pancreatic cancer.
Standard 3 + 3 dose escalation shall be employed; two dose levels of nintedanib will be explored 150 mg BiD and 200 mg BiD.
one cycle (14 days) of nintedanib monotherapy followed by a total of eight cycles (28 days) of both nintedanib plus gemcitabine plus nab-paclitaxel
nintedanib : twice daily dose by mouth // 12 hours apart
Gemcitabine: intravenous dosing on days 1, 8, 15 of the 28 day cycle
nab-paclitaxel: intravenous dosing on days 1, 8, 15 of the 28 day cycle
1. Signed and dated written informed consent prior to admission to the study;
1. Histologically or cytologically confirmed metastatic or locally advanced adenocarcinoma of the pancreas;
3. At least one measurable disease lesion according to Response Evaluation Criteria In Solid Tumors (RECIST, version 1.1);
4. Age >= 18 years;
5. No more than one prior line of non-gemcitabine/nab-paclitaxel containing systemic therapy for metastatic/locally advanced pancreatic cancer;
6. Eastern Cooperative Oncology Group (ECOG) Performance Score of 0-1;
7. Women of childbearing potential must have a negative pregnancy test ( serum) within 14 days prior to registration; (Note: contraception in patients with reproductive capacity will be considered to be of childbearing potential unless surgically sterilized by hysterectomy or bilateral tubal ligation/salpingectomy, or post-menopausal for at least two years.)
8. Adequate biological parameters at baseline (obtained within 14 days prior to registration).
Absolute Neutrophil Count (ANC) >=1,500 cells/mm3
Platelets >=100,000 cells/mm3
Hemoglobin >=9 g/dl
AST (SGOT) / ALT (SGPT) AST and ALT <= 1.5 x ULN (2.5 x ULN in case of liver metastases)
Total Bilirubin <= ULN
INR <= 2
PT / PTT <= 50% increase from institutional ULN
Serum Creatinine <= 1.5 x ULN
If elevated liver function tests develop at the time of initial presentation or develop during workup and are the result of mechanical obstruction of the biliary drainage by tumor compression or invasion, a biliary drain may be placed. If drainage allows the liver function tests to come within inclusion criteria, the patient may be enrolled.