A Randomized, Double Blind, Placebo Controlled, Phase II Study Evaluating the Efficacy and Safety of RP101 in Combination with Gemcitabine Administered as First-Line Treatment to Subjects with Unresectable, Locally Advanced, or Metastatic Pancreatic Adenocarcinoma

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2007-004102-27-HU
• Date of registration: 09/01/2008
• Prospective Registration: Yes
• Primary sponsor: SciClone Pharmaceuticals, Inc.
• Public title: A Randomized, Double Blind, Placebo Controlled, Phase II Study Evaluating the Efficacy and Safety of RP101 in Combination with Gemcitabine Administered as First-Line Treatment to Subjects with Unresectable, Locally Advanced, or Metastatic Pancreatic Adenocarcinoma
• Scientific title: A Randomized, Double Blind, Placebo Controlled, Phase II Study Evaluating the Efficacy and Safety of RP101 in Combination with Gemcitabine Administered as First-Line Treatment to Subjects with Unresectable, Locally Advanced, or Metastatic Pancreatic Adenocarcinoma
• Date of first enrolment: 20/02/2008
• Target sample size: 153
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-004102-27
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: yes Other trial design description: Gemcitabine will be used as background treatment If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: yes Other specify the comparator: Gemcitabine will be used as background treatment

Countries of recruitment

Germany, Hungary, Netherlands, Spain

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male or female subjects 19 years of age or older
2. Subjects with a histologically or cytologically confirmed diagnosis of adenocarcinoma of the pancreas that is unresectable, locally advanced or metastatic
3. ECOG performance status 0 or 1
4. Life expectancy of at least 3 months
5. Documentation of all sites of pancreatic cancer disease withing 28 days prior to treatment start by CT or spiral CT or MRI scan of chest, abdomen, brain (only if clinical suspicion of metastasis), and other scans necessary. Negative scans performed within 35 days of randomization do not need to be repeated
6. Adequate hematological, renal, and hepatic function within 14 days prior to treatment start defined as follows:
-Hemoglobin (HGB) = 9.0 gm/dL (prior transfusion and/or support with erythropoietin-based products is acceptable)
-Absolute granulocyte count = 1.5 x 109/L (1500 cells/mm3) unsupported for 1 week by growth factors
-Platelet count = 100 x 109/L (100,000/mm3) non-platelet transfusion dependent
-Serum creatinine < 1.5 times the upper limit of normal
-Total bilirubin < 2.0 times the upper limit of normal
-ALT (SGPT) < 2.0 times the upper limit of normal and/or AST (SGOT) < 2.0 times the upper limit of normal. If clearly attributable to liver metastasis, ALT and/or AST < 5.0 times the upper limit of normal is permitted
7. Capability of understanding the objectives of the study and giving written informed consent
8. Willingness and ability to comply with the study protocol for the duration of the study
9. Capability to have sufficient oral caloric and fluid intake and to take oral study medications
10. If subject is female and of child bearing potential she must have a negative ß-HCG urine test within 72 hours prior to receiving treatment. Being of child bearing potential is defined as any female subject who does not meet at least one of the following criteria: a) has undergone bilateral salpingo-oophorectomy and/or hysterectomy; b) is greater than age 50 years and has not had a menstrual period for at least 24 months
11. All potentially fertile subjects, both female and male, must practice a medically approved method of contraception or agree to abstinence for the duration of participation in the active treatment phase of the study and for a period of 4 weeks after the last administration of either study drug


Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Prior history of other malignant tumors, except non-melanoma skin cancer or in situ cervical carcinoma curatively excised. Subject may be included if disease-free of cancers other than pancreatic cancer for 5 years
2. Major surgery within 2 weeks prior to treatment start
3. Any prior cytotoxic chemotherapy other than 5-FU (+/- folinic acid) or gemcitabine given concurrently with radiation treatment as a “radiosensitizer”. 5-FU must not have been given within 21 days prior to randomization.
4. Radiation treatment within 4 weeks of treatment start. Prior radiation treatment for management of local disease is allowed, provided that local disease progression or progression by new measurable metastasis outside of the radiation portal is documented by imaging procedure, all toxicities resolved, and the last fraction of radiation treatment was completed at least 4 weeks prior to treatment start.
5. Uncontrolled cardiac atrial or ventricular arrhythmias (New York Heart Association (NYHA) congestive heart failure = class 2; uncontrolled hypertension; pulmonary embolism or cerebrovascular accident (CVA) within 6 months
6. Neurologic: symptomatic motor or sensory neurotoxicity grade = 2 of National Cancer Institute Common Toxicity Criteria (NCI-CTC)
7. Central nervous system metastasis
8. Psychiatric disabilities, seizures or central nervous system disorders thought to be clinically significant in the opinion of the Investigator that could interfere with informed consent or compliance with the protocol
9. Active bleeding Grade = 2 of NCI-CTC
10. Serious (Grade 3-4 of NCI-CTC) active infections at time of treatment start
11. Subjects with known allergies or intolerance to RP101 or similar compounds
12. Subjects with known allergies or intolerance to gemcitabine
13. Participation in any investigational drug study with investigational drug exposure within 4 weeks prior to treatment start
14. Pregnant or breast feeding women
15. Gastrointestinal (GI) tract disease resulting in an inability to take oral medication, such as uncontrolled inflammatory GI diseases (eg, Crohn’s disease, ulcerative colitis) or postsurgical malabsorption characterized by uncontrolled diarrhea that results in weight loss and vitamin deficiency or requires IV hyperalimentation (however, use of pancreatic enzyme supplementation is allowed provided that the above criteria are not met) resulting in an inability to take oral medication
16. Known to be seropositive for human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV). Testing is not required in the absence of clinical signs and symptoms suggestive of HIV infection or acute or chronic hepatitis
17. Any condition which in the judgment of the Investigator would place the subject at undue risk or interfere with the results of the study (eg, low medical risks because of non-malignant organ or systemic disease, or secondary effects of cancer)
18. Uncontrolled cancer pain.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

metastatic pancreatic cancer
MedDRA version: 9.1 Level: LLT Classification code 10033605 Term: Pancreatic cancer metastatic
MedDRA version: 9.1 Level: LLT Classification code 10033606 Term: Pancreatic cancer non-resectable

Intervention(s)

Trade Name: Helpin RP101 (BVDU)
Product Name: Brivudin (BVDU)
Product Code: RP101
Pharmaceutical Form: Tablet
INN or Proposed INN: BRIVUDINE
CAS Number: 69304478
Current Sponsor code: RP101
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 190-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Trade Name: Gemzar
Product Name: Gemzar 200/-1000
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: GEMCITABINE
CAS Number: 95058814
Current Sponsor code: GEMZAR
Concentration unit: mg/m2 milligram(s)/square meter
Concentration type: equal
Concentration number: 1000 -

Primary Outcome(s)

Secondary Objective: - To compare progression-free survival (PFS) between the two treament arms
- To compare the two treatment groups with respect to overall tumor response rates (ORR) which is the sum of the complete respone (CR) and partial response (PR) rates as assessed by the Response Evalulation Criteria in Solid Tumors (RECIST) in subjects with measurable disease at baseline
- To compare the two treatment arms with respect to disease control rates (DCR) which is the sum of CR, PR and stable disease (SD) rates as assessed by RECIST in subjects with measurable disease at baseline
- To compare the CR rates between the two treatment arms
- To evaluate the CA 19-9 levels as a marker of disease response
- To compare changes in ECOG performance status between the two treatment arms
- To evaluate the safety of RP101

Primary end point(s): The primary efficacy endpoint will be overall survival defined as the time from randomization to death from any cause or last contact if alive

Main Objective: To compare the overall survival (OS) distributions of RP101 and gemcitabine to placebo and gemcitabine in subjects with unresectable, locally advanced or metastatic pancreatic adenocarcinoma.

Secondary ID(s)

SCI-RP-Pan-P2-001