Combination Therapy With NC-6004 and Gemcitabine Versus Gemcitabine Alone in Pancreatic Cancer

NCT ID: NCT02043288

Last Updated: 2020-04-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 310 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-01-31
• Study Completion Date: 2019-12-31

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

Conditions

Pancreatic Neoplasms

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

NC-6004 and Gemcitabine combination

NC-6004 90mg/m2 i.v. on Day 1 and Gemcitabine 1000mg/m2 i.v. on Day 1 and Day 8 respectively

Group Type: EXPERIMENTAL

NC-6004

Intervention Type: DRUG

Study group (3 week/cycle):

NC-6004 90 mg/m2 i.v. inf. over 60 min on Day 1

Gemcitabine

Intervention Type: DRUG

Study group (3 week/cycle):

Gemcitabine 1000 mg/m2 i.v. inf. over 30 min on Day 1 and Day 8 (follow by administration of NC-6004)

Control group (4 week/cycle):

Gemcitabine 1000 mg/m2 i.v. inf. over 30 min on Day 1, Day 8 and Day 15

Gemcitabine monotherapy

Gemcitabine 1000mg/m2 i.v. on Day 1 ,8 and 15

Group Type: ACTIVE_COMPARATOR

Gemcitabine

Intervention Type: DRUG

Study group (3 week/cycle):

Gemcitabine 1000 mg/m2 i.v. inf. over 30 min on Day 1 and Day 8 (follow by administration of NC-6004)

Control group (4 week/cycle):

Gemcitabine 1000 mg/m2 i.v. inf. over 30 min on Day 1, Day 8 and Day 15

Interventions

NC-6004

Study group (3 week/cycle):

NC-6004 90 mg/m2 i.v. inf. over 60 min on Day 1

Intervention Type: DRUG

Gemcitabine

Study group (3 week/cycle):

Gemcitabine 1000 mg/m2 i.v. inf. over 30 min on Day 1 and Day 8 (follow by administration of NC-6004)

Control group (4 week/cycle):

Gemcitabine 1000 mg/m2 i.v. inf. over 30 min on Day 1, Day 8 and Day 15

Intervention Type: DRUG

Other Intervention Names

Micelplatin; Gemzar

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

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

NanoCarrier Co., Ltd.

INDUSTRY

Sponsor Role: collaborator

Orient Europharma Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Li-Tzong Chen, M.D., Ph. D.

Role: PRINCIPAL_INVESTIGATOR

National Institute of Cancer Research, National Health Research Institutes

Locations

Prince of Wales Hospital

Hong Kong, , Hong Kong

Queen Mary Hospital

Hong Kong, , Hong Kong

Aichi Cancer Center

Aichi, , Japan

Chiba Cancer Center

Chiba, , Japan

National Hospital Organization Kyushu Cancer Center

Fukuoka, , Japan

Hokkaido University Hospital

Hokkaido, , Japan

National Hospital Organization Osaka National Hospital

Osaka, , Japan

Osaka Medical Center for Cancer and Cardiovascular Diseases

Osaka, , Japan

Saitama Cancer Center

Saitama, , Japan

National Hospital Organization Shikoku Cancer Center

Shikokuchūō, , Japan

Shizuoka Cancer Center

Shizuoka, , Japan

Center Hospital of the National Center for Global Health and Medicine

Tokyo, , Japan

Kyorin university Hospital

Tokyo, , Japan

National Cancer Center Hospital East

Tokyo, , Japan

National Cancer Center Hospital

Tokyo, , Japan

The Cancer Institute Hospital of JFCR

Tokyo, , Japan

The University of Tokyo Hospital

Tokyo, , Japan

Kanagawa Cancer Center

Yokohama, , Japan

Hospital Sultan Ismail

Johor Bahru, , Malaysia

Hospital Kuala Lumpur

Kuala Lumpur, , Malaysia

Makati Medical Center

Makati, , Philippines

National Cancer Centre

Singapore, , Singapore

Ajou University Hospital (AUH)

Gyeonggi-do, , South Korea

Samsung Medical Center (SMC)

Seoul, , South Korea

The Catholic University of Korea, Seoul St. Mary's Hospital (CUK SSMH)

Seoul, , South Korea

Korea University Guro Hospital (KUGH)

Seoul, , South Korea

Yonsei University Health System, Severance Hospital

Seoul, , South Korea

Chiayi Chang Gung Memorial Hospital

Chiayi City, , Taiwan

Kaohsiung Medical University Hospital

Kaohsiung City, , Taiwan

Chang Gung Memorial Hospital, Kaohsiung Branch

Kaohsiung City, , Taiwan

China Medical University Hospital

Taichung, , Taiwan

Taichung Veterans General Hospital

Taichung, , Taiwan

National Cheng Kung University Hospital

Tainan City, , Taiwan

Chi Mei Hospital

Tainan City, , Taiwan

Mackay Memorial Hospital

Taipei, , Taiwan

National Taiwan University Hospital

Taipei, , Taiwan

Taipei Medical University Hospital

Taipei, , Taiwan

Koo Foundation Sun Yat-Sen Cancer Center

Taipei, , Taiwan

Taipei Veterans General Hospital

Taipei, , Taiwan

Tri-Service General Hospital

Taipei, , Taiwan

Taipei Medical University-Shuang-Ho Hospital, Ministry of Health and Welfare

Taipei, , Taiwan

Chang Gung Memorial Hospital, Linkou Branch

Taipei, , Taiwan

Chi Mei Medical Center

Yongkang District, , Taiwan

Countries

Hong Kong; Japan; Malaysia; Philippines; Singapore; South Korea; Taiwan

Other Identifiers

NC-6004-005

Identifier Type: -

Identifier Source: org_study_id