Gemcitabine, Cisplatin, Epirubicin, and Capecitabine in Treating Patients With Stage I-II Resectable Pancreatic Cancer

NCT ID: NCT01150630

Last Updated: 2017-09-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 98 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-05-31
• Study Completion Date: 2017-08-31

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.

Conditions

Pancreatic Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

adjuvant PEXG

cisplatin and epirubicin at 30 mg/mq, gemcitabine at 800 mg/mq and capecitabine at 1250 mg/mq/day per os for 14 days every 14 days for 6 months

Group Type: EXPERIMENTAL

capecitabine

Intervention Type: DRUG

1250 mg/mq/day per os for 14 days every 14 days for 6 months

cisplatin

Intervention Type: DRUG

30 mg/mq every 14 days for 6 months

epirubicin

Intervention Type: DRUG

30 mg/mq every 14 days for 6 months

gemcitabine

Intervention Type: DRUG

ARM A: 1000 mg/mq for 3 weekly infusions every 4 weeks for 6 months ARM B and C: 800 mg/mq every 14 days for 6 months

perioperative PEXG

cisplatin and epirubicin at 30 mg/mq, gemcitabine at 800 mg/mq and capecitabine at 1250 mg/mq/day per os for 14 days every 14 days for 3 months before surgery and 3 months after surgery

Group Type: EXPERIMENTAL

capecitabine

Intervention Type: DRUG

1250 mg/mq/day per os for 14 days every 14 days for 6 months

cisplatin

Intervention Type: DRUG

30 mg/mq every 14 days for 6 months

epirubicin

Intervention Type: DRUG

30 mg/mq every 14 days for 6 months

gemcitabine

Intervention Type: DRUG

ARM A: 1000 mg/mq for 3 weekly infusions every 4 weeks for 6 months ARM B and C: 800 mg/mq every 14 days for 6 months

Adjuvant Gemcitabine

Adjuvant Gemcitabine at 1000 mg/mq for 3 weeks every 4 weeks for 6 months

Group Type: ACTIVE_COMPARATOR

gemcitabine

Intervention Type: DRUG

ARM A: 1000 mg/mq for 3 weekly infusions every 4 weeks for 6 months ARM B and C: 800 mg/mq every 14 days for 6 months

Interventions

capecitabine

1250 mg/mq/day per os for 14 days every 14 days for 6 months

Intervention Type: DRUG

cisplatin

30 mg/mq every 14 days for 6 months

Intervention Type: DRUG

epirubicin

30 mg/mq every 14 days for 6 months

Intervention Type: DRUG

gemcitabine

ARM A: 1000 mg/mq for 3 weekly infusions every 4 weeks for 6 months ARM B and C: 800 mg/mq every 14 days for 6 months

Intervention Type: DRUG

Other Intervention Names

XELODA; cisplatino TEVA; farmorubicina; GEMZAR

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

IRCCS San Raffaele

OTHER

Sponsor Role: lead

Responsible Party

Michele Reni

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Michele Reni, MD

Role: PRINCIPAL_INVESTIGATOR

Istituto Scientifico H. San Raffaele

Locations

Istituto Scientifico H. San Raffaele

Milan, , Italy

Countries

Italy

References

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.

Reference Type: DERIVED

PMID: 29625841 (View on PubMed)

Other Identifiers

PACT-15

Identifier Type: OTHER

Identifier Source: secondary_id

2010-019942-23

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CDR0000675485

Identifier Type: -

Identifier Source: org_study_id