Clinical trial NCT02043288: Combination Therapy With NC-6004 and Gemcitabine Versus Gemcitabine Alone in Pancreatic Cancer
Official title: A Phase III, Open-label, Randomized Study of the Combination Therapy With NC-6004 and Gemcitabine Versus Gemcitabine Alone in Patients With Locally Advanced or Metastatic Pancreatic Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pancreatic Neoplasms
Keywords: Pancreatic cancer
Platinum
Micelle
Lead sponsor: Orient Europharma Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: NanoCarrier Co., Ltd.
First posted: 2014-01-23
Enrollment: 310
Sex: ALL
Minimum age (years): 20
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This clinical trial is designed to evaluate the impact of the addition of NC-6004 to gemcitabine in the treatment of patients with locally advanced or metastatic pancreatic cancer in Asian countries.

Detailed description: Pancreatic cancer is one of the most deadly cancers because of the predominately late diagnosis. Gemcitabine (GEM) is the standard treatment for advanced and metastatic pancreatic cancer. According to preclinical data and few early phase studies, a combined use of gemcitabine and cisplatin (CDDP) showed synergistic efficacy against pancreatic cancer. NC-6004, a novel micellar cisplatin formulation, retains the activity but avoids the renal toxicity and neurotoxicity caused by the high peak Cmax concentrations of cisplatin. This trial is designed to evaluate the impact of the addition of NC-6004 to gemcitabine in the treatment of patients with locally advanced or metastatic pancreatic cancer.

The main hypothesis of this study is that NC-6004 plus gemcitabine combination is superior to gemcitabine alone in terms of overall survival in locally advanced or metastatic pancreatic cancer patients

Eligibility criteria: Inclusion criteria:

1. Male or female aged between 20 to 80 years (inclusive)
2. Unresectable, histologically or cytologically confirmed, locally advanced or metastatic pancreatic cancer (adenocarcinoma, adenosquamous carcinoma or poorly differentiated carcinoma)
3. Presence of at least one measurable tumor lesion (longest diameter ≥ 10 mm)
4. No prior systemic anti-cancer therapy\* and radiotherapy\*\* for advanced pancreatic cancer

   \* Patients with post-operative adjuvant chemotherapy other than platinum products (e.g. cisplatin, carboplatin and oxaliplatin, etc.) or radiotherapy or chemo-radiotherapy completed more than 6 months before recurrence will be eligible.

   \*\* Patients with prior palliative radiotherapy of \< 20% bone marrow involvement prior to 6 months from screening will be eligible.
5. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1
6. Adequate organ function defined as:

   * 3,000 cells/μL ≤ WBC ≤ 12,000 cells/μL
   * Absolute neutrophils count (ANC) ≥ 1,500 cells/μL
   * Platelets ≥ 100,000 cells/μL
   * Hemoglobin (Hb) ≥ 9.0 g/dL
   * Alanine amino transferase (ALT) and aspartate amino transferase (AST) ≤ 2.5 times the upper limit of normal (ULN) in patients with no demonstrable hepatic metastasis, or ≤ 5 x ULN in patients with hepatic metastasis
   * Serum bilirubin ≤ 1.5 x ULN in patients with no demonstrable hepatic metastasis and obstructive jaundice, or ≤ 2.5 x ULN in patients with hepatic metastasis or obstructive jaundice
   * Serum creatinine (SCr) ≤ 1.5 mg/dL and creatinine clearance (CrCl) ≥ 60 mL/min (from 24-hour urine test or Cockcroft-Gault formula)
   * Corrected serum calcium ≤ ULN
7. If fertile\*, willing to use barrier contraception till 6 months after the end of treatment

   \* With the following exceptions: 1) pre-menopausal females with bilateral tubal ligation, bilateral oophorectomy or hysterectomy; 2) post-menopausal women, defined as 12 months of spontaneous amenorrhea; 3) males with vasectomy.
8. Willing and able to comply with study procedures and provide written informed consent

Exclusion criteria:

1. Pregnancy or breastfeeding
2. Active concomitant malignancy or history of other cancer except carcinoma in situ of cervical squamous cell carcinoma, stage I colon cancer or other malignance that has remained disease-free for more than 3 years after curative intervention
3. Metastasis to the central nervous system or brain
4. Evidence of hearing impaired ≥ Grade 2 as assessed by pure tone audiometry or other neurotoxicity ≥ Grade 2

   \* Patients with age-associated hearing loss at the high frequencies that, in the judgment of the investigator, would not interfere significantly with patient's safety or study assessments will be eligible to enroll.
5. Patient with pulmonary fibrosis or interstitial pneumonia
6. Marked pleural effusion or ascites above Grade 2
7. Patient with known HIV infection
8. Patient with active hepatitis B, hepatitis C or any other ongoing severe infections
9. Patient with severe mental disorder
10. As judged by the investigator, any evidence of significant laboratory findings or severe/uncontrolled clinical disorders (e.g. dementia, myocardial infarction within 6 months prior to enrollment, New York Heart Association (NYHA) Class III or IV heart failure, unstable angina, active cardiomyopathy, unstable arrhythmia, and other unstable or uncompensated respiratory, cardiac, hepatic, renal and/or infectious disease)
11. Patient with known hypersensitivity to Pt compounds
12. Known severe drug hypersensitivity
13. Treatment with a non-approved or investigational product within 30 days before Day 1 of study treatment
14. Alcoholic liver disease\* or liver disease with obvious clinical symptom or sign

    \* the investigator should judge from medical examination by interview and laboratory test including γ-GTP, AST and ALT
15. Daily Alcohol consumption within 6 months before the screening as an average weekly intake of \>21 units (168 g of pure alcohol) or an average daily intake of \>3 units (24 g of pure alcohol) for males / an average weekly intake of \>14 units (112 g of pure alcohol) or an average daily intake of \>2 units (16 g of pure alcohol) for females.

    Kind of Alcohol Alcohol Percentage mL per 1 unit =8 g of pure alcohol

    Beer 5 % 200 mL

    Whiskey/Brandy 40 % 25 mL

    Wine 12 % approx. 83 mL

    Sake 15 % approx. 67 mL

    Distilled spirit 25 % 40 mL

    Kaoliang 50 % 20 mL
16. Patient with uncontrolled diabetes
17. Radiotherapy within 6 months before screening
18. Experienced Abdominal Radiotherapy
19. Experienced treatment of Gemtuzumab ozogamicin
20. Patient with autoimmune hepatitis or idiopathic thrombocytopenic purpura (ITP)
21. Observation of "attenuated or reversed hepatic venous portal blood flow\*" was confirmed by doppler ultrasonography or CT (recommend evaluation in arterial phase, portal-venous phase and equilibrium phase) of the liver \* On doppler ultrasonography of right and left branch of portal vein, blood flow is measured as about 0 mL/min or between plus and minus, which indicate obvious blood flow obstruction

Primary outcomes:
measure: Overall survival (OS)
timeFrame: 3.5 years
Secondary outcomes:
measure: Progression free survival (PFS)
timeFrame: 3.5 years
measure: Response rate (RR) and disease control rate (DCR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria
timeFrame: 3.5 years
measure: Duration of response
timeFrame: 3.5 years
measure: CA19-9
timeFrame: 3.5 years
measure: Quality of life (QoL) using EORTC QLQ-C30
timeFrame: 3.5 years
Other outcomes:
Locations:
city: Hong Kong
country: Hong Kong
facility: Prince of Wales Hospital
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
city: Aichi
country: Japan
facility: Aichi Cancer Center
city: Chiba
country: Japan
facility: Chiba Cancer Center
city: Fukuoka
country: Japan
facility: National Hospital Organization Kyushu Cancer Center
city: Hokkaido
country: Japan
facility: Hokkaido University Hospital
city: Osaka
country: Japan
facility: National Hospital Organization Osaka National Hospital
city: Osaka
country: Japan
facility: Osaka Medical Center for Cancer and Cardiovascular Diseases
city: Saitama
country: Japan
facility: Saitama Cancer Center
city: Shikokuchūō
country: Japan
facility: National Hospital Organization Shikoku Cancer Center
city: Shizuoka
country: Japan
facility: Shizuoka Cancer Center
city: Tokyo
country: Japan
facility: Center Hospital of the National Center for Global Health and Medicine
city: Tokyo
country: Japan
facility: Kyorin university Hospital
city: Tokyo
country: Japan
facility: National Cancer Center Hospital East
city: Tokyo
country: Japan
facility: National Cancer Center Hospital
city: Tokyo
country: Japan
facility: The Cancer Institute Hospital of JFCR
city: Tokyo
country: Japan
facility: The University of Tokyo Hospital
city: Yokohama
country: Japan
facility: Kanagawa Cancer Center
city: Gyeonggi-do
country: Korea, Republic of
facility: Ajou University Hospital (AUH)
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center (SMC)
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Seoul St. Mary's Hospital (CUK SSMH)
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital (KUGH)
city: Seoul
country: Korea, Republic of
facility: Yonsei University Health System, Severance Hospital
city: Johor Bahru
country: Malaysia
facility: Hospital Sultan Ismail
city: Kuala Lumpur
country: Malaysia
facility: Hospital Kuala Lumpur
city: Makati
country: Philippines
facility: Makati Medical Center
city: Singapore
country: Singapore
facility: National Cancer Centre
city: Chiayi City
country: Taiwan
facility: Chiayi Chang Gung Memorial Hospital
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Hospital
city: Kaohsiung
country: Taiwan
facility: Chang Gung Memorial Hospital, Kaohsiung Branch
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Tainan
country: Taiwan
facility: Chi Mei Hospital
city: Taipei
country: Taiwan
facility: Mackay Memorial Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Medical University Hospital
city: Taipei
country: Taiwan
facility: Koo Foundation Sun Yat-Sen Cancer Center
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taipei
country: Taiwan
facility: Tri-Service General Hospital
city: Taipei
country: Taiwan
facility: Taipei Medical University-Shuang-Ho Hospital, Ministry of Health and Welfare
city: Taipei
country: Taiwan
facility: Chang Gung Memorial Hospital, Linkou Branch
city: Yongkang
country: Taiwan
facility: Chi Mei Medical Center
Study officials:
affiliation: National Institute of Cancer Research, National Health Research Institutes
name: Li-Tzong Chen, M.D., Ph. D.
role: PRINCIPAL_INVESTIGATOR
References: