Phase 2 Study of S-1 in Advanced or Metastatic Pancreatic Cancer - Full Text View

Sponsors and Collaborators:	Taiho Pharma USA, Inc. Quintiles United Biosource Corporation
Information provided by:	Taiho Pharma USA, Inc.
ClinicalTrials.gov Identifier:	NCT00651742

Purpose

The purpose of this study is to determine whether S-1 is effective in slowing tumor activity in patients with locally advanced or metastatic pancreatic cancer who have not had chemotherapy. The study is also looking at the safety of S-1.

Condition	Intervention	Phase
Locally Advanced or Metastatic Pancreatic Cancer	Drug: S-1	Phase II

MedlinePlus related topics: Cancer Pancreatic Cancer

Drug Information available for: S 1 (Combination)

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label, Single Group Assignment, Efficacy Study
Official Title:	An Open-Label, Non-Randomized, Multicenter, Two-Stage, Phase 2 Study of S-1 in Chemotherapy-Naïve Patients With Locally Advanced or Metastatic Pancreatic Cancer

Further study details as provided by Taiho Pharma USA, Inc.:

Primary Outcome Measures:

Overall tumor response rate (ORR - the proportion of patients with objective evidence of PR or CR) [ Time Frame: Each cycle will last 21 days (14 days treatment, 7 days recovery) for 1 year, unless patient is still on treatment, or at the time of death, whichever occurs first. Tumor assessments will be obtained at baseline and at the end of every even cycle. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To evaluate the disease control rate (DCR), duration of response (DR), time to tumor progression (TTP), and survival rate [ Time Frame: Each cycle will last 21 days (14 days treatment, 7 days recovery) for 1 yr, unless pt is still on treatment, or at the time of death. Pts will be followed for survival status every 2 mos following PD for up to 1 yr ] [ Designated as safety issue: No ]
To investigate the effect of S-1 on Karnofsky Performance Status (KPS) and pain assessments, including pain intensity and analgesic consumption [ Time Frame: Each cycle will last 21 days for up to 1 yr. KPS measured at baseline; w/in 24 hrs prior to drug (Day 1) for cycles after Cycle 1; end of treatment. Pts complete pain diary at 7 days prior to Day 1 of Cycle 1 and cont'ing through end of treatment. ] [ Designated as safety issue: No ]
To evaluate the safety profile of S-1 [ Time Frame: AEs will be reported through f/up ; blood/urine will be collected at baseline, Days 8&15, w/in 24 hrs of study drug on Day 1 of each cycle after Cycle 1; at end of study treatment ] [ Designated as safety issue: Yes ]
To investigate the relationship of S-1 plasma levels (components and metabolites) with safety and efficacy parameters [ Time Frame: Each cycle will last 21 days (14 days reatment, 7 days recovery). Blood samples to be obtained 1.5 ± 0.5 h, 5 ± 1 h, 7 ± 1 h postdose on Day 1 of Cycle 1 only ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	40
Study Start Date:	February 2006
Estimated Study Completion Date:	November 2009
Estimated Primary Completion Date:	November 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental All patients will receive S-1 orally at a dose of 30 mg/m2 twice daily (BID) for 14 days followed by a 1-week recovery period, repeated every 3 weeks.	Drug: S-1 All patients will receive S-1 orally at a dose of 30 mg/m2 twice daily (BID) for 14 days followed by a 1-week recovery period, repeated every 3 weeks. The trial will proceed to the second stage only if sufficient efficacy is demonstrated in Stage 1.

Detailed Description:

Locally advanced or metastatic pancreatic cancer is relatively unresponsive to chemotherapy. This is true for the nucleoside analogue gemcitabine, with a response rate of approximately 10%, as well as for 5-fluorouracil (5-FU). Even when gemcitabine is combined with other chemotherapeutic drugs or biological agents, the overall tumor response rate remains basically unchanged. S-1 is a new generation oral fluoropyrimidine that combines Tegafur (5-fluoro-1-(tetrahydro-2-furanyl)-2,4(1H,3H)-pyrimidinedione [FT]), an oral prodrug of 5-FU, with two modulators, Gimeracil (5-chloro-2,4-dihydroxypyridine [CDHP]), which inhibits 5-FU degradation by dihydropyrimidine dehydrogenase (DPD) inhibition, and Oteracil potassium (Oxo), which inhibits 5-FU phosphorylation in the digestive tract. This combination of 3 compounds is designed to achieve enhanced antitumor activity while decreasing gastrointestinal toxicity.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

1. Has provided written informed consent. 2. Has histologically or cytologically confirmed locally advanced, unresectable or metastatic adenocarcinoma of the pancreas not amenable to curative radiotherapy or surgery.

3. Has measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria (ie, lesions that can be accurately measured in at least one dimension with the longest diameter ≥ 20 mm using conventional techniques or ≥ 10 mm using spiral computed tomography [CT] scan).

4. Is able to take medications orally. 5. Is 18 years of age or older. 6. Has a Karnofsky Performance Status (KPS) ≥ 70% (see Appendix A). 7. Has a life expectancy of ≥ 12 weeks. 8. Has adequate organ function as defined by the following criteria:
1. Transaminases AST (SGOT) and ALT (SGPT) ≤ 2.5 times the upper limit of normal (ULN). If liver function abnormalities are due to underlying liver metastasis, then AST (SGOT) and ALT (SGPT) may be ≤ 5 times ULN.
2. Total serum bilirubin ≤ 3.0 times ULN (if due to underlying liver metastasis, then total bilirubin may be ≤ 5 times ULN).
3. Absolute granulocyte count ≥ 1,500/mm3 (ie, ≥ 1.5 x 109/L by International Units [IU]).
4. Platelet count ≥ 100,000/mm3 (IU: ≥ 100 x 109/L).
5. Hemoglobin value ≥ 9.0 g/dL.
6. Calculated creatinine clearance ≥ 60 mL/min (based on serum creatinine) (Cockcroft-Gault85 formula) 9. Is willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
  
  Exclusion Criteria:
1. Has had treatment with any of the following within the specified time frame prior to study drug administration:
1. Any prior anticancer chemotherapy.
2. Radiation therapy to a target lesion unless there was evidence of PD after radiotherapy (and this target lesion must not be the only site of measurable disease).
3. Any radiotherapy within the previous 3 weeks.
4. Any investigational agent received either concurrently or within the last 30 days.
5. Current enrollment in another clinical study with an investigational agent. Patients participating in surveys or observational studies are eligible to participate in this study.
  
  2. Major surgery within the previous 3 weeks. 3. Symptomatic brain metastasis not controlled by corticosteroids. 4. Leptomeningeal metastasis. 5. Previous or concurrent malignancy other than pancreatic cancer except adequately treated carcinoma in-situ of the cervix or non-melanoma skin cancer. 6. Uncontrolled ascites requiring drainage at least twice a week. 7. Other serious illness or medical condition(s) including, but not limited to, the following:
1. Uncontrolled congestive heart failure (New York Heart Association [NYHA] Class III or IV), angina pectoris, arrhythmias, or hypertension.
2. Active infection.
3. Known (at time of entry) gastrointestinal disorder, including malabsorption, chronic nausea, vomiting, or diarrhea, present to the extent that it might interfere with oral intake and absorption of study medication.
4. Poorly controlled diabetes mellitus.
5. Psychiatric disorder that may interfere with consent and/or protocol compliance.
6. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness.
7. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the Investigator would make the patient inappropriate for entry into this study.
  
  8. Is receiving a concomitant treatment with drugs interacting with S-1. The following drugs are prohibited because there may be an interaction with S-1:
1. Sorivudine, uracil, cimetidine, folinic acid, and dipyridamole (may enhance S-1 activity).
2. Allopurinol (may diminish S-1 activity).
3. Phenytoin (S-1 may enhance phenytoin activity).
4. Flucytosine, a fluorinated pyrimidine antifungal agent (may enhance S-1 and flucytosine activity).
  
  9. Is a pregnant or lactating female. 10. Has known sensitivity to 5-FU. 11. Is a patient with reproductive potential who refuses to use an adequate means of contraception (including male patients).

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00651742

Sponsors and Collaborators

Taiho Pharma USA, Inc.

Quintiles

United Biosource Corporation

Investigators

Study Director:

Peter Urrea, PhD

Taiho Pharma USA, Inc.

More Information

Responsible Party:	Taiho Pharma USA, Inc. ( Peter Urrea/Senior VP, Clinical and Regulatory Affairs )
Study ID Numbers:	TPU-S1204
Study First Received:	March 31, 2008
Last Updated:	April 2, 2008
ClinicalTrials.gov Identifier:	NCT00651742
Health Authority:	United States: Food and Drug Administration; Germany: Federal Institute for Drugs and Medical Devices

Study placed in the following topic categories:

Digestive System Diseases
Digestive System Neoplasms
Pancreatic Neoplasms
Endocrine System Diseases

Pancreatic Diseases
Gastrointestinal Neoplasms
Endocrinopathy
Endocrine Gland Neoplasms

Additional relevant MeSH terms:

Neoplasms
Neoplasms by Site

ClinicalTrials.gov processed this record on January 16, 2009