Study of CG200745 PPA in Combination With Gemcitabine and Erlotinib for Advanced Pancreatic Cancer

A Phase I/II Study of Combination Therapy of CG200745 PPA With Gemcitabine and Erlotinib to Determine the Maximum Tolerated Dose (MTD) and Evaluate the Safety and Efficacy for Locally Advanced Unresectable, or Metastatic Pancreatic Cancer

<Part I - Phase I trial>

The phase I clinical trial is to identify the MTD (Maximum Tolerated Dose) and DLT (Dose Limiting Toxicity) of CG200745 PPA in combination use of Gemcitabine and Erlotinib. Initial dose of CG200745 PPA is 187.5 mg/m^2, and it will be extended to 250 mg/m^2, 312.5 mg/m^2 or it will be reduced to 125 mg/m^2 based on the results of the cohort of 3 subjects per dose level.

Based on the 3+3 dose escalation study design, Gemcitabine and Erlotinib are administered as fixed doses, whereas CG200745 PPA is to be administered as in four different cohorts according to the dose level. Each cohort consists of 3 or 6 subjects.

<Part II - Phase II trial>

In the phase II clinical trial, the subjects will be administered with the dose which is to be identified as a recommended dose based on the results of Phase I study. The whole one cycle is consisted of 28 days, same as the phase I. The entire treatment period is 6 cycles and tumor assessment is evaluated every 2 cycles.

<Part I - Phase I trial>

The phase I clinical trial is to identify the MTD and DLT of CG200745 PPA in combination use of Gemcitabine and Erlotinib. Initial dose of CG200745 PPA is 187.5 mg/m^2, and it will be extended to 250 mg/m^2, 312.5 mg/m^2 or it will be reduced to 125 mg/m^2 based on the results of the cohort of 3 subjects per dose level.

Based on the 3+3 dose escalation study design, Gemcitabine and Erlotinib are administered as fixed doses, whereas CG200745 PPA is to be administered as in four different cohorts according to the dose level. Each cohort consists of 3 or 6 subjects.

• Dose level 0: CG200745 PPA 125 mg/m^2 puls Gemcitabine 1000 mg/m^2) and Erlotinib 100 mg
• Dose level 1: CG200745 PPA 187.5 mg/m^2 puls Gemcitabine 1000 mg/m^2) and Erlotinib 100 mg
• Dose level 2: CG200745 PPA 250 mg/m^2 puls Gemcitabine 1000 mg/m^2) and Erlotinib 100 mg
• Dose level 3: CG200745 PPA 312.5 mg/m^2 puls Gemcitabine 1000 mg/m^2) and Erlotinib 100 mg

<Part II - Phase II trial>

In the phase II clinical trial, the subjects will be administered with the dose which is to be identified as a recommended dose based on the results of Phase I study. The whole one cycle is consisted of 28 days, same as the phase I. The entire treatment period is 6 cycles and tumor assessment is evaluated every 2 cycles.

Inclusion Criteria:

• Ages: ≥ 20 and ≤ 75 years

• Subjects who join voluntarily for participation in the study, sign the consent form and are willing to comply the clinical trial procedure

• Subjects who have diagnosed with unresectable, locally advanced, metastatic, histologically and cytologically confirmed pancreatic adenocarcinoma

• ECOG (Eastern Cooperative Oncology Group) performance status: 0-2

• Estimated life expectancy at the time of enrollment is more than 3 months

• Adequate hematological, renal and hepatic function

  • Absolute neutrophil count (ANC) ≥ 1500/mm3, hemoglobin ≥ 9.0 g/dl (eligible if hemoglobin lab values are adjusted with blood transfusion), platelet ≥ 100,000/mm3

  • Within normal range of serum creatinine or creatinine clearance rate (CCr) ≥ 60 ml/min (using Cockcroft-Gault equation )

  • Subjects who have no abnormal serum electrolyte values (including calcium, magnesium, phosphorous and potassium). However, the supplementation therapy is allowed for normalization of serum electrolytes.

    ※ Normal reference range for Calcium: 8.3~10.5 mg/dl, Magnesium: 1.58~3.0 mg/dl, Phosphorous: 2.4~4.5 mg/dl, Potassium: 3.3~5.5 mmol/L

  • Serum bilirubin < 2 x Upper Limit Normal (ULN), Aspartate Aminotransferase (AST)/Alanine Aminotransferase (ALT) < 2.5 x ULN, Alkaline phosphatase (ALP) < 5 x ULN (If liver metastasis, AST/ALT <5 x ULN)

  • Prothrombin Time (PT) or Partial thromboplastin time (PTT) ≤ 1.5 x ULN (except for the use of anticoagulant, in this case, PT/PTT stabilization for up to 2 weeks should be confirmed)

• No prior chemotherapy, radiation or biologics

Exclusion Criteria:

• Subject who had experienced a major surgery within 2 weeks prior to the screening visit
• Subject with an evidence for uncontrolled brain metastasis (except for the patients with radiologically and neurologically stable brain metastasis without corticosteroid therapy for at least two weeks)
• Subject who cannot be administered oral drug, or have difficulty to absorb the study drugs due to a history of major gastrointestinal surgery or pathological findings.
• Subjects who have treated antibiotics within last seven days due to an active bacterial infection prior to the enrollment. (Topical antibiotic therapies are excluded)
• Subjects who had experienced any malignancies within past 5 years, except for basal cell skin cancer, in situ cervical cancer, or papillary thyroid tumor.
• Pregnancy or Lactating
• Fertile subjects who do not agree with the effective contraception during the study period and up to 3 months after the completion of the study. The following cases are exceptions: an irreversible and surgical sterility by hysterectomy, bilateral oophorectomy or bilateral salpingectomy, and menopausal women over 50 years old with no menstruation for at least 12 months and without hormonal therapy. Tubal ligation is not regarded as an effective contraception
• Subject who cannot take anti-cancer chemotherapy due to a systemic disease (ex. chronic renal failure)
• Subjects who have treated with any other investigational drug within 4 weeks prior to the screening visit
• History of hypersensitivity to study drug
• Subject with HIV positive