This is a phase i/iiB, multi-institution prospective open label study in which up to 34 subjects with metastatic, locally advanced unresectable or recurrent pancreatic cancer who failed or did not tolerate chemotherapy with FoLFiRinoX will be enrolled into one of two parts.
PaRT 1: PHaSe i
During Part 1 of the study, the safe and tolerable dose of nPC-1C(neo-102) monoclonal antibody therapy in combination with Gemcitabine will be determined. The initial portion of this protocol will be a phase i (3+3) design with two dose levels of up to 6 subjects per cohort.
Dose Level Gemcitabine nPC-1C(neo-102)
1 1000 mg/m2 iv (D1, 8, 15) 1.5 mg/kg iv (D1, 15)
Dose Level Gemcitabine nPC-1C(neo-102)
-1 1000 mg/m2 iv (D1, 8, 15) 1 mg/kg iv (D1, 15)
Part 2: Phase iiB
upon completion of the Phase i component of the study, up to 28 patients will be evaluated in the expansion cohort, including 6 from the Phase i portion, to explore clinical response.
1000 mg/m2 iv (D1, 8, 15) 1.5 or 1 mg/kg i.v. (as determined in Phase i) (D1, 15)
Status of Protocol at Conclusion of Part i
Three subjects were enrolled and received nPC-1C 1.5 mg/kg on Days 1 and 15, with Gemcitabine 1000 mg/m2 on Days 1, 8 and 15 for a 28 day cycle. all three subjects completed the 28 day toxicity evaluation without DLT. Toxicities observed included: anemia (grade 3) possibly related to nPC-1C; fatigue (grade 3), hyperglycemia (grade 3) and anorexia (grade 3) unlikely related to nPC-1C; anemia (grade 3), thrombocytopenia (grade 4) unlikely related to nPC-1C and likely related to gemcitabine. Hence, the nPC-1C dose for Part 2 of this study is 1.5 mg/kg for subsequent subject enrollment.
1. Subjects with recurrent, locally advanced unresectable or metastatic adenocarcinoma of the pancreas who have progressed after primary therapy; must have progressed after FOLFIRINOX or FOLFIRINOX-like regimen or were intolerant of it. FOLFIRINOX regimen is defined as follows: oxaliplatin, 85 mg/m2; irinotecan, 180 mg/m2; leucovorin, 400 mg mg/m2 fluorouracil, 400 mg/m2 given as a bolus followed by 2400 mg/m2 given as a 46-hour continuous infusion, every 2 weeks. FOLFIRINOX xlike regimen could consist of 5-FU/leucovorin or xeloda, combined with either irinotecan, oxaliplatin or both. FOLFIRINOX intolerance is defined as inability to tolerate the FOLFIRINOX regimen due to side effects and or toxicities determined by the treating medical oncologist.
The histology of the primary tumor should be confirmed at NCI or the other participating sites.
2. IHC: >= 20% of tumor on tissue sections must stain with NPC-1C.
3. Age: >= 18 years of age.
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (Appendix A).
5. Have an anticipated life expectancy of greater than 12 weeks.
6. Patients must have recovered from any acute toxicity related to prior therapy. Toxicity should be <= grade 1 or <= grade 2 for peripheral neuropathy, or returned to baseline.
7. If female, is post-menopausal, surgically sterilized or willing to use an effective method of contraception (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, or condom with spermicide, or abstinence) for the duration of the study and for 3 months after the end of treatment. If male, has agreed to use barrier method for contraception for the duration of the study and for 3 months after the end of treatment.
8. Patient must be willing to sign a written informed consent
9. Laboratory tests meet minimum safety requirements:
* Hemoglobin >= 8.5 g/dL (may be receiving supportive therapy)
* ANC >= 1,500 K/uL
* Platelets >= 100 K/uL
* Total bilirubin <= 2 mg/dL
* ALT/AST <= 3 times ULN or <= 5 times ULN in the setting of liver metastases
* Creatinine <= 1.5 mg/dL or creatinine clearance > 40 mL/min/1.73 m2 for patients with creatinine levels above institutional normal, as calculated by the Cockcroft Gault formula.