QUILT-3.010: A Study of Gemcitabine and Nab-paclitaxel With or Without NPC-1C to Treat Patients With Pancreatic Cancer

A Multicenter Phase I/II Randomized Phase II Study of Gemcitabine and Nab-Paclitaxel With or Without NPC-1C in Patients With Metastatic or Locally Advanced Pancreatic Cancer Previously Treated With FOLFIRINOX

This was a Phase 1/2 multi-institution prospective open label study in which subjects with metastatic, locally advanced unresectable or recurrent pancreatic cancer who previously received treatment with chemotherapy with FOLFIRINOX or FOLFIRINOX-like regimen received the investigational agent NEO-102 (NPC-1C).

The Phase 1 portion of this study evaluated the safety of NEO-102 in combination with Gemcitabine in a dose de-escalation design with a starting dose of 1.5 mg/kg/dose. If 2 of 6 patients experience DLT, the dose will be de-escalated to 1 mg/kg/dose to evaluate the safety of NEO-102 in combination with Gemcitabine. .

In the Phase 2 portion patients were randomized into one of two arms:

A: NPC-1C with gemcitabine and nab-paclitaxel or B: gemcitabine and nab-paclitaxel

During Part 1 of the study, the safe and tolerable dose of NEO-102 in combination with Gemcitabine will be determined using a dose de-escalation design. The starting dose of NEO-102 is 1.5 mg/kg/dose (Dose level 1). If 2 of 6 patients experience a DLT at the starting dose, the dose of NEO-102 will be de-escalated to 1 mg/kg/dose, and up to 6 patients will be treated at this Dose Level -1. Upon completion of the phase I study up to 90 patients be randomized to one of two arms:

A: Patients will receive NPC-1C(NEO-102) infusion at the safe dose, and nab-paclitaxel (125 mg/m2 as a 30 minute infusion, maximum infusion time not to exceed 40 minutes) followed by gemcitabine (1000 mg/m2 as a 30 minute infusion) for 3 consecutive weeks (on Day 1, 7 and 15 ) followed by a week of rest (for a 28 day cycle).

OR B: Patients will receive on Day 1, 7 and 15 nab-paclitaxel (125 mg/m2 as a 30 minute infusion, maximum infusion time not to exceed 40 minutes) followed by gemcitabine (1000 mg/m2 as a 30 minute infusion) for 3 consecutive weeks (on Day 1, 7 and 15). NPC-1C(NEO-102) infusion at a dose of 1.5mg/kg IV 30 minutes following the completion of the gemcitabine on days 1 and 15 of the 28 day cycle.

Inclusion Criteria

• Subjects with recurrent, locally advanced unresectable or metastatic adenocarcinoma of the pancreas who have progressed after primary therapy with FOLFIRINOX or FOLFIRINOX-like regimen or were intolerant of it.

• IHC greater than or equal to 20 percent of tumor on tissue sections must stain with NPC-1C.

• 18 years of age or older.

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

• Have an anticipated life expectancy of greater than 8 weeks.

• Have recovered from any acute toxicity related to prior therapy.

• If female, is post-menopausal, surgically sterilized or willing to use an effective method of contraception 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.

• Must be willing to sign a written informed consent.

• Laboratory tests must meet minimum safety requirements

  1. Hemoglobin greater than or equal to 8.5 g/dL (may be receiving supportive therapy)
  2. ANC greater than or equal to 1,500 K/uL
  3. Platelets greater than or equal to 100 K/uL
  4. Total bilirubin less than or equal to 2 mg/dL
  5. ALT/AST less than or equal to 3 times ULN or less than or equal to 5 times ULN in the setting of liver metastases.
  6. Creatinine less than or equal to 1.5 mg/dL or creatinine clearance greater than 40 mL/min/1.73 m2 for patients with creatinine levels above institutional normal, as calculated by the Cockcroft Gault formula.

• Men and women of all races and ethnic groups are eligible for this trial.

Exclusion Criteria

• Have received a second line chemotherapy after progressing on or not tolerating treatment with FOLFIRINOX as a first line. Prior adjuvant/neoadjuvant gemcitabine or gemcitabine-based radiation will not be counted as first line therapy.
• Have known brain metastases.
• Have had any major surgery within four weeks of enrollment.
• Have greater than grade 2 ascites at time of enrollment.
• Have received Gemcitabine for palliative treatment or progressed while receiving it or is within 3 months of completion in the adjuvant setting.
• Have uncontrolled concomitant illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia.
• Have serious medical or psychiatric illness that could, in the Investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
• Must not have other invasive malignancies within the past 3 years (with the exception of non-melanoma skin cancers or non-invasive bladder cancer).
• Is pregnant or breast-feeding, since the effects of NPC-1C on the developing human fetus and nursing infants are unknown and potentially harmful, women of child-bearing potential must agree to use adequate contraception (hormonal or double barrier method of birth control or complete abstinence) prior to study entry, for the duration of study participation, and for three months after the last dose of investigational agent.
• Have had any chemotherapy or systemic corticosteroids within 2 weeks of study entry.
• Have acquired, hereditary or congenital immunodeficiencies including cellular immunodeficiencies, hypogammaglobulinemia and dysgammaglobulinemia.
• Have a prior history of a documented hemolytic event.
• Have a history of hypersensitivity to human or mouse antibody products.
• Have a known history of HIV are excluded due to the possibility that Gemcitabine or NPC-1C(NEO-102) may worsen their condition and the likelihood that the underlying condition may obscure the attribution of adverse events with respect to Gemcitabine or NPC-1C(NEO-102).