Clinical trial NCT01150630: Gemcitabine, Cisplatin, Epirubicin, and Capecitabine in Treating Patients With Stage I-II Resectable Pancreatic Cancer
Official title: Randomized Phase II-III Trial of Peri- or Post-Operative Chemotherapy in Resectable Pancreatic Adenocarcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pancreatic Cancer
Keywords: adenocarcinoma of the pancreas
stage I pancreatic cancer
stage II pancreatic cancer
Lead sponsor: IRCCS San Raffaele
Sponsor class: OTHER
First posted: 2010-06-25
Enrollment: 98
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy, such as gemcitabine hydrochloride, cisplatin, epirubicin hydrochloride, and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving gemcitabine hydrochloride, with or without cisplatin, epirubicin hydrochloride, and capecitabine before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving these drugs after surgery may kill any tumor cells that remain after surgery.

PURPOSE: This randomized phase II/III trial is studying how well gemcitabine hydrochloride, with or without cisplatin, epirubicin hydrochloride, and capecitabine, works when given before and/or after surgery in treating patients with stage I or stage II pancreatic cancer that can be removed by surgery.

Detailed description: OBJECTIVES:

Primary

* To assess the proportion of patients who are event-free (defined as disease progression, local recurrence, distant metastasis, new tumor, or death) at 1 year after neoadjuvant therapy comprising gemcitabine hydrochloride with cisplatin, epirubicin hydrochloride, and capecitabine (PEXG), and adjuvant chemotherapy comprising gemcitabine hydrochloride or PEXG regimen in patients with resectable stage I or II adenocarcinoma of the pancreas. (phase II)
* To assess whether the best experimental regimen, which will be selected on the basis of the phase II part of the trial, is able to improve overall survival when compared to standard adjuvant gemcitabine in these patients. (phase III)

Secondary

* To assess radiological, biochemical, and pathological response rate (neoadjuvant arm only) in these patients.
* To assess surgical resection rate, surgical mortality and morbidity, and proportion of patients with negative surgical margins.
* To assess lymph node status in these patients.
* To determine tolerability of these regimens in these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to center. Patients are randomized to 1 of 3 treatment arms.

* Arm I (adjuvant gemcitabine hydrochloride) : Patients receive gemcitabine hydrochloride IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days for 6 months in the absence of disease progression or unacceptable toxicity.
* Arm II (adjuvant cisplatin, epirubicin hydrochloride, gemcitabine hydrochloride, and capecitabine \[PEXG regimen\]): Patients receive cisplatin IV over 1 hour on days 1-5, epirubicin hydrochloride IV on days 1 and 8, gemcitabine hydrochloride IV over 1 hour on days 1 and 8, and oral capecitabine on days 1-14. Treatment repeats every 14 days for 6 months in the absence of disease progression or unacceptable toxicity.
* Arm III (neoadjuvant and adjuvant PEXG regimen): Patients receive neoadjuvant cisplatin IV over 1 hour on days 1-5, epirubicin hydrochloride IV on days 1 and 8, gemcitabine hydrochloride IV over 1 hour on days 1 and 8, and oral capecitabine on days 1-14. Treatment repeats every 14 days for up to 3 months. Patients then undergo surgery for pancreatic cancer followed by adjuvant (within 2 months of surgery) PEXG given as in neoadjuvant therapy. Treatment with adjuvant PEXG repeats every 14 days for 3 months in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 1 year, every 4 months for 2 years, and then every 6 months thereafter.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically or cytologically\* confirmed adenocarcinoma of pancreas

  * Stage I-II disease
  * Resectable disease
* No superior mesenteric vein or artery, portal vein, celiac trunk, or hepatic artery infiltration
* No symptomatic duodenal stenosis
* NOTE: Patients without histological or cytological results may be allowed provided ≥ 1 attempt has been made by needle aspiration with negative imaging and clinical signs suggestive of adenocarcinoma.

PATIENT CHARACTERISTICS:

* Karnofsky performance status 70-100%
* WBC ≥ 3,500/mm³
* ANC ≥ 1,500/mm³
* Platelet count ≥ 100,000/mm³
* Hemoglobin ≥ 10 g/dL
* Creatinine ≤ 1.5 mg/dL
* ALT and AST ≤ 3 times upper limit of normal
* Bilirubin ≤ 3 mg/dL
* No prior or concurrent malignancy within the past 5 years except for surgically cured carcinoma in situ of the cervix or basal cell or squamous cell carcinoma of the skin
* Not pregnant or nursing
* No psychological, familial, sociological, or geographical condition that would potentially hinder study compliance or follow-up schedule

PRIOR CONCURRENT THERAPY:

* No prior chemotherapy or radiotherapy for pancreatic adenocarcinoma
* No other concurrent experimental drugs

Primary outcomes:
measure: Event-free survival at 1 year (phase II)
timeFrame: every 3 months
Secondary outcomes:
measure: Radiological, biochemical, and pathological response rate (neoadjuvant arm only)
timeFrame: after 3 months of induction therapy
measure: Surgical resection rate
timeFrame: immediately after surgery
measure: Surgical mortality and morbidity
timeFrame: immediately after surgery
measure: Tolerability
timeFrame: every 2 weeks during therapy
measure: Proportion of patients with negative surgical margins
timeFrame: immediately after surgery
measure: Lymph node status
timeFrame: immediately after surgery
Other outcomes:
Locations:
city: Milan
country: Italy
facility: Istituto Scientifico H. San Raffaele
Study officials:
affiliation: Istituto Scientifico H. San Raffaele
name: Michele Reni, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Reni M, Balzano G, Zanon S, Zerbi A, Rimassa L, Castoldi R, Pinelli D, Mosconi S, Doglioni C, Chiaravalli M, Pircher C, Arcidiacono PG, Torri V, Maggiora P, Ceraulo D, Falconi M, Gianni L. Safety and efficacy of preoperative or postoperative chemotherapy for resectable pancreatic adenocarcinoma (PACT-15): a randomised, open-label, phase 2-3 trial. Lancet Gastroenterol Hepatol. 2018 Jun;3(6):413-423. doi: 10.1016/S2468-1253(18)30081-5. Epub 2018 Apr 4.