Metronomic Chemotherapy With Capecitabine for Pancreatic Cancer

Pancreatic Cancer Clinical Trial

Official title:

A Multi-center, II Phase，Randomized Controlled Clinical Study of Capecitabine Metronomic Chemotherapy After Gemcitabine Plus Capecitabine Standard Adjuvant Therapy for Stage II/III Pancreatic Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03959150
• Other study ID #: Metro-PC
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: January 5, 2020
• Est. completion date: June 30, 2023

Study information

• Verified date: April 2021
• Source: Ruijin Hospital
• Contact: Jun Zhang, MD & Ph. D
• Phone: +86-13818332497
• Email: junzhang10977[@]sjtu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The latest guidelines recommend Gemcitabine plus Capecitabine as the first choice of adjuvant chemotherapy for pancreatic cancer patients in good physical condition. In order to prolong the survival of patients and improve the cure rate, metronomic chemotherapy with capecitabine is a safe, effective and economical treatment mode after adjuvant chemotherapy. This study is trying to determine that compared with observation group, if capecitabine metronomic medication is a better choice after adjuvant chemotherapy.

Description:

Capecitabine (Xeloda ®) is currently the most biologically active oral fluoropyrimidine drug, and is widely used in adjuvant therapy for pancreatic cancer. It is usually taken twice a day (in the morning and in the evening) for 2 weeks, followed by a 1 week break before repeating the next dosage cycle. In this study, capecitabine will be prescribed as dosage of 500mg/m2, and maintain for a whole year after the standard treatment in stage II/III pancreatic cancer patients. 1 year disease-free survival is set as the primary outcome, OS, RFS, AEs and exploratory biomarkers including effects of metronome chemotherapy on immune cells, such as NK cells, T cells, TAMs, B cells, etc are also observed as the secondary outcomes. Statistical analysis are made to see compared with observation group, whether this metronomic therapy of capecitabine ( 500mg/m2) will bring benefit to pancreatic cancer patients.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 231
• Est. completion date: June 30, 2023
• Est. primary completion date: June 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Histologically confirmed pancreatic invasive ductal adenocarcinoma.

2. The patient underwent surgery for pancreatic tumor resection, and no gross residual lesions were found postoperatively (R2).

3. Stage II/III pancreatic cancer was determined according to AJCC/UICC TNM stage eighth.

4. At least 6 cycles of gemcitabine plus capecitabine chemotherapy have been completed.

5. Age 18-70 years old, gender not limited.

6. ECOG performance score is 0 or 1.

7. Without dysphagia, able to tolerate oral administration.

8. No relevant clinical or imaging evidence of recurrence or metastasis showing within the 28 days before random.

9. Chemotherapy with capecitabine combined with gemcitabine regimen was given within 12 weeks after surgery, and last chemotherapy to random time = 6 weeks.

10. Adequate bone marrow, liver, and kidney function in measurements taken within 7 days before registration :

11. Hemoglobin = 90 g/L, Platelet count = 100×109/L, Absolute granulocyte count = 1.5×109/L.

i. Note: patients should not receive blood transfusion or growth factor support within 14 days before collection of blood samples.

12. Serum creatinine= 1.5 ULN, and calculated creatinine clearance of = 60 mL/min/1.73m2.

13. AST and ALT = 2.5 X ULN, serum total bilirubin = 1.5 X ULN (Patients with Gilbert syndrome with total bilirubin= 3 X ULN can be enrolled).

14. INR or PT = 1.5×ULN,unless the patient is receiving anticoagulant therapy and the PT value is within the expected therapeutic range of the anticoagulant.

15. Electrocardiogram and cardiac function were not contraindicated in chemotherapy.

16. Women should have a negative pregnancy test, and all the patients have no planning within 3 years and should take contraceptive measures during treatment.

17. Informed consent form signed.

Exclusion Criteria:

1. Other pathological types of pancreatic malignancies (e.g. neuroendocrine carcinoma, large cell carcinoma, signet ring cell carcinoma, etc.).

2. With distant metastasis or malignant pleural effusion.

3. Pregnant and breast-feeding women.

4. Unable to oral medication.

5. Previous or concurrent malignancies, excluding curatively treated in situ carcinoma of the cervix or non-melanoma skin cancer, unless at least 5 years have elapsed since last treatment and the patient is considered cured.

6. A history of transient ischemic attack, cerebrovascular accident, thrombosis, or thromboembolism (pulmonary embolism or deep venous thrombosis) within 180 days before randomization.

7. Any of the following uncontrolled or severe cardiovascular disease history:

8. Myocardial infarction occurred 180 days before randomization.

9. Uncontrolled angina occurred within 180 days before randomization.

10. Heart failure of class III or IV (according to New York Heart Association functional classification).

11. Uncontrolled hypertension after appropriate treatment (e.g. Systolic blood pressure =150mmHg or diastolic blood pressure =90mmHg for 24h or longer).

12. Arrhythmias that require treatment, including pacemakers.

13. Serious drug allergy.

14. Uncontrolled diabetes or systemic infection.

15. Known dihydro pyrimidine dehydrogenase (DPD) deficiency.

16. Any other reasons the investigator considers the patient should not participate in the study.

17. Without personal freedom and independent civil capacity.

18. Already enrolled into other clinical trials.

Related Conditions & MeSH terms

• Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

Drug:
• Capecitabine
Oral fluorouracil

Locations

Country	Name	City	State
China	Department of Oncology, Ruijin Hospital	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Ruijin Hospital

Country where clinical trial is conducted

China, 

References & Publications (14)

Ansari D, Gustafsson A, Andersson R. Update on the management of pancreatic cancer: surgery is not enough. World J Gastroenterol. 2015 Mar 21;21(11):3157-65. doi: 10.3748/wjg.v21.i11.3157. Review. — View Citation

Burris HA 3rd, Moore MJ, Andersen J, Green MR, Rothenberg ML, Modiano MR, Cripps MC, Portenoy RK, Storniolo AM, Tarassoff P, Nelson R, Dorr FA, Stephens CD, Von Hoff DD. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol. 1997 Jun;15(6):2403-13. — View Citation

Ferrone CR, Pieretti-Vanmarcke R, Bloom JP, Zheng H, Szymonifka J, Wargo JA, Thayer SP, Lauwers GY, Deshpande V, Mino-Kenudson M, Fernández-del Castillo C, Lillemoe KD, Warshaw AL. Pancreatic ductal adenocarcinoma: long-term survival does not equal cure. Surgery. 2012 Sep;152(3 Suppl 1):S43-9. doi: 10.1016/j.surg.2012.05.020. Epub 2012 Jul 3. — View Citation

Javle M, Hsueh CT. Updates in Gastrointestinal Oncology - insights from the 2008 44th annual meeting of the American Society of Clinical Oncology. J Hematol Oncol. 2009 Feb 23;2:9. doi: 10.1186/1756-8722-2-9. — View Citation

Kalser MH, Ellenberg SS. Pancreatic cancer. Adjuvant combined radiation and chemotherapy following curative resection. Arch Surg. 1985 Aug;120(8):899-903. Erratum in: Arch Surg 1986 Sep;121(9):1045. — View Citation

Khorana AA, Mangu PB, Berlin J, Engebretson A, Hong TS, Maitra A, Mohile SG, Mumber M, Schulick R, Shapiro M, Urba S, Zeh HJ, Katz MHG. Potentially Curable Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol. 2017 Jul 10;35(20):2324-2328. doi: 10.1200/JCO.2017.72.4948. Epub 2017 Apr 11. — View Citation

Liao WC, Chien KL, Lin YL, Wu MS, Lin JT, Wang HP, Tu YK. Adjuvant treatments for resected pancreatic adenocarcinoma: a systematic review and network meta-analysis. Lancet Oncol. 2013 Oct;14(11):1095-1103. doi: 10.1016/S1470-2045(13)70388-7. Epub 2013 Sep 12. Review. — View Citation

Narang AK, Miller RC, Hsu CC, Bhatia S, Pawlik TM, Laheru D, Hruban RH, Zhou J, Winter JM, Haddock MG, Donohue JH, Schulick RD, Wolfgang CL, Cameron JL, Herman JM. Evaluation of adjuvant chemoradiation therapy for ampullary adenocarcinoma: the Johns Hopkins Hospital-Mayo Clinic collaborative study. Radiat Oncol. 2011 Sep 28;6:126. doi: 10.1186/1748-717X-6-126. — View Citation

Neoptolemos JP, Moore MJ, Cox TF, Valle JW, Palmer DH, McDonald AC, Carter R, Tebbutt NC, Dervenis C, Smith D, Glimelius B, Charnley RM, Lacaine F, Scarfe AG, Middleton MR, Anthoney A, Ghaneh P, Halloran CM, Lerch MM, Oláh A, Rawcliffe CL, Verbeke CS, Campbell F, Büchler MW; European Study Group for Pancreatic Cancer. Effect of adjuvant chemotherapy with fluorouracil plus folinic acid or gemcitabine vs observation on survival in patients with resected periampullary adenocarcinoma: the ESPAC-3 periampullary cancer randomized trial. JAMA. 2012 Jul 11;308(2):147-56. doi: 10.1001/jama.2012.7352. Erratum in: JAMA. 2012 Nov 14;308(18):1861. — View Citation

Neoptolemos JP, Palmer DH, Ghaneh P, Psarelli EE, Valle JW, Halloran CM, Faluyi O, O'Reilly DA, Cunningham D, Wadsley J, Darby S, Meyer T, Gillmore R, Anthoney A, Lind P, Glimelius B, Falk S, Izbicki JR, Middleton GW, Cummins S, Ross PJ, Wasan H, McDonald A, Crosby T, Ma YT, Patel K, Sherriff D, Soomal R, Borg D, Sothi S, Hammel P, Hackert T, Jackson R, Büchler MW; European Study Group for Pancreatic Cancer. Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): a multicentre, open-label, randomised, phase 3 trial. Lancet. 2017 Mar 11;389(10073):1011-1024. doi: 10.1016/S0140-6736(16)32409-6. Epub 2017 Jan 25. — View Citation

Oettle H, Neuhaus P, Hochhaus A, Hartmann JT, Gellert K, Ridwelski K, Niedergethmann M, Zülke C, Fahlke J, Arning MB, Sinn M, Hinke A, Riess H. Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: the CONKO-001 randomized trial. JAMA. 2013 Oct 9;310(14):1473-81. doi: 10.1001/jama.2013.279201. — View Citation

Siravegna G, Bardelli A. Blood circulating tumor DNA for non-invasive genotyping of colon cancer patients. Mol Oncol. 2016 Mar;10(3):475-80. doi: 10.1016/j.molonc.2015.12.005. Epub 2015 Dec 17. Review. — View Citation

Uesaka K, Boku N, Fukutomi A, Okamura Y, Konishi M, Matsumoto I, Kaneoka Y, Shimizu Y, Nakamori S, Sakamoto H, Morinaga S, Kainuma O, Imai K, Sata N, Hishinuma S, Ojima H, Yamaguchi R, Hirano S, Sudo T, Ohashi Y; JASPAC 01 Study Group. Adjuvant chemotherapy of S-1 versus gemcitabine for resected pancreatic cancer: a phase 3, open-label, randomised, non-inferiority trial (JASPAC 01). Lancet. 2016 Jul 16;388(10041):248-57. doi: 10.1016/S0140-6736(16)30583-9. Epub 2016 Jun 2. — View Citation

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* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	One year disease-free survival	was defined as the rate of disease recurrence, metastasis or death due to disease progression within 1 year after the surgery	1 year
Secondary	Overall Survival (OS)	was defined as the time from the date of surgery until the date of any death occurred	5 year
Secondary	Recurrence-free Survival (RFS)	was defined as the time from the date of surgery until the date of local recurrence of the tumor	1 year
Secondary	AEs	Hand and foot syndrome and other treatment related AE	5 year
Secondary	Exploratory biomarkers	including effects of metronome chemotherapy on immune cells, such as NK cells, T cells, TAMs, B cells, etc	1 yaer