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

Pancreatic Neoplasms Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02043288
• Other study ID #: NC-6004-005
• Status: Completed
• Phase: Phase 3
• Start date: January 2014
• Est. completion date: December 2019

Study information

• Verified date: April 2020
• Source: Orient Europharma Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 310
• Est. completion date: December 2019
• Est. primary completion date: December 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 80 Years

Eligibility

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 ?-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

Related Conditions & MeSH terms

• Pancreatic Neoplasms

Intervention

Drug:
• NC-6004
Study group (3 week/cycle): NC-6004 90 mg/m2 i.v. inf. over 60 min on Day 1
• 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

Locations

Country	Name	City	State
Hong Kong	Prince of Wales Hospital	Hong Kong
Hong Kong	Queen Mary Hospital	Hong Kong
Japan	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	Shikokuchuo
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	Tokyo
Japan	National Cancer Center Hospital East	Tokyo
Japan	The Cancer Institute Hospital of JFCR	Tokyo
Japan	The University of Tokyo Hospital	Tokyo
Japan	Kanagawa Cancer Center	Yokohama
Korea, Republic of	Ajou University Hospital (AUH)	Gyeonggi-do
Korea, Republic of	Korea University Guro Hospital (KUGH)	Seoul
Korea, Republic of	Samsung Medical Center (SMC)	Seoul
Korea, Republic of	The Catholic University of Korea, Seoul St. Mary's Hospital (CUK SSMH)	Seoul
Korea, Republic of	Yonsei University Health System, Severance Hospital	Seoul
Malaysia	Hospital Sultan Ismail	Johor Bahru
Malaysia	Hospital Kuala Lumpur	Kuala Lumpur
Philippines	Makati Medical Center	Makati
Singapore	National Cancer Centre	Singapore
Taiwan	Chiayi Chang Gung Memorial Hospital	Chiayi City
Taiwan	Chang Gung Memorial Hospital, Kaohsiung Branch	Kaohsiung
Taiwan	Kaohsiung Medical University Hospital	Kaohsiung
Taiwan	China Medical University Hospital	Taichung
Taiwan	Taichung Veterans General Hospital	Taichung
Taiwan	Chi Mei Hospital	Tainan
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	Chang Gung Memorial Hospital, Linkou Branch	Taipei
Taiwan	Koo Foundation Sun Yat-Sen Cancer Center	Taipei
Taiwan	Mackay Memorial Hospital	Taipei
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Taipei Medical University Hospital	Taipei
Taiwan	Taipei Medical University-Shuang-Ho Hospital, Ministry of Health and Welfare	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei
Taiwan	Tri-Service General Hospital	Taipei
Taiwan	Chi Mei Medical Center	Yongkang

Sponsors (2)

Lead Sponsor	Collaborator
Orient Europharma Co., Ltd.	NanoCarrier Co., Ltd.

Countries where clinical trial is conducted

Hong Kong,  Japan,  Korea, Republic of,  Malaysia,  Philippines,  Singapore,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival (OS)	Overall survival is defined as the time from the treatment initiation until death from any cause, and censored at the last follow up time.	3.5 years
Secondary	Progression free survival (PFS)	Progression free survival is defined as the time from the treatment initiation until progression or death, and censored at the last follow up time.	3.5 years
Secondary	Response rate (RR) and disease control rate (DCR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria	Response rate is defined as counts and proportions of patients responding complete response or partial response within the duration of the study.; Disease control rate is defined as counts and proportions of patients responding complete response, partial response or progressive disease within the duration of the study.	3.5 years
Secondary	Duration of response	Duration of overall response (DOR) will be measured from the time of initial response (CR or PR) until documented progression or death, and censored at last follow up time.; Duration of stable disease (DSD) will be measured from the time of initial stable disease (SD) until documented progression or death, and censored at last follow up time.	3.5 years
Secondary	CA19-9	CA19-9 values and changes from baseline will be summarized.	3.5 years
Secondary	Quality of life (QoL) using EORTC QLQ-C30	Quality of life (QoL) values and changes from baseline will be summarized.	3.5 years