A Multicenter Randomized Phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus Gemcitabine and nab-Paclitaxel alone in Patients with Metastatic or Locally Advanced Pancreatic Cancer Previously Treated with FOLFIRINOX

Summary

This is a randomized phase ii, multi-institution prospective open label study in which up to 90 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 arms a and B.

Status of Protocol and rationale for amendment F
This protocol was originally designed as a single-arm study evaluating the combination of Gemcitabine and nPC-1C (neo-102) as a second line therapy in subjects with metastatic, locally advanced unresectable or recurrent pancreatic cancer previously treated with FoLFiRinoX or a FoLFiRinoX-like regimen. 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 established for the Phase 2 component of this study was 1.5 mg/kg for subsequent subject enrollment. Two patients have been enrolled and treated in the Phase 2 component of this study at Montefiore Medical Center with the combination of Gemcitabine and nPC-1C/neo-102. The first patient completed six cycles of therapy and achieved stable disease post cycle 2 and post cycle 4. The second patient continues on treatment and completed Cycle 4 Day 21 to date. The patient was re-staged at Cycle 3 Day 1 and had stabilization of disease. There have been no reported Saes to date for either patient.

Participant Eligibility

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 (including if administered in adjuvant setting). 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 8 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.