Maintenance Therapy With Sunitinib or Observation in Metastatic Pancreatic Cancer (PACT-12)

Maintenance Therapy With Sunitinib or Observation in Metastatic Pancreatic Cancer: a Phase II Randomized Trial.

RATIONALE: Sunitinib malate may stop the growth of tumor cells by blocking some of the tyrosine kinases needed for angiogenesis and cell growth. It is not yet known whether sunitinib malate is effective as maintenance therapy in delaying tumor progression in patients with metastatic pancreatic cancer who are progression-free after 6 months of induction chemotherapy.

PURPOSE: This randomized phase II trial is studying sunitinib malate as maintenance therapy to see how well it works compared with observation in avoiding tumor progression after induction chemotherapy in patients with metastatic pancreatic cancer.

Study Overview

• Status: Completed
• Conditions: Pancreatic Cancer
• Intervention / Treatment: Drug: sunitinib

Detailed Description

OBJECTIVES:

• Compare the 6-month progression-free survival of patients with metastatic pancreatic cancer without progression after 6 months of induction chemotherapy treated with sunitinib malate as maintenance therapy vs observation.

OUTLINE: This is a multicenter study. Patients are randomized to 1 of 2 treatment arms:

• Arm I: Patients receive oral sunitinib malate once daily for up to 6 months in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients undergo observation only.

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Milan, Italy, 20132
    • San Raffaele Scientific Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Pathologically confirmed metastatic pancreatic adenocarcinoma

  • Stage IV disease
• Received chemotherapy for a duration of 6 months

• No progressive disease for ≥ 6 months since beginning of induction chemotherapy (irrespective of regimen and response: stable disease, partial response, or complete response) demonstrated by the following:

  • Two consecutive CT or MR scans separated by ≥ 6 weeks
  • Normal or no CA19.9 increase > 20% during the last month

PATIENT CHARACTERISTICS:

• Karnofsky Performance Status 50-100%
• Adequate bone marrow, liver, and kidney function
• Normal thyroid gland function (euthyroid)
• Not pregnant or nursing
• No duodenal, gastric, or intestinal infiltration
• Able to take oral medication

• None of the following conditions related to cardiac disease, failure, or vascular disease including any of the following:

  • QTc interval prolongation
  • Congestive heart failure
  • Serious cardiac arrhythmias
  • Active coronary artery disease
  • Myocardial infarction
  • Ischemia
  • Cerebrovascular accident
  • Evidence of pre-existing uncontrolled hypertension
• No other malignancies except surgically cured carcinoma in situ of the cervix, basal or squamous cell carcinoma of the skin, or other adequately treated neoplasms for which the patient has been disease-free for ≥ 5 years

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No other prior chemotherapy apart from first-line treatment for pancreatic cancer
• More than 3 weeks and less than 8 weeks since prior chemotherapy (> 1 week in the case of fluorouracil as continuous infusion or capecitabine)

• No prior antiangiogenesis drugs, including any of the following:

  • Sunitinib malate
  • Sorafenib
  • Bevacizumab
  • AZD2171
  • Vatalanib
  • VEGF trap
  • Pazopanib
• More than 1 month since prior major surgical procedure and completely recovered
• More than 7-12 days since prior and no concurrent drugs that are known CYP3A4 inhibitors
• No concurrent drugs with potential anti-arrhythmic activity
• No concurrent thrombolytic agent at therapeutical dose
• No concurrent treatment with other experimental drugs

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
NO_INTERVENTION: observation; no therapy until progression
EXPERIMENTAL: sunitinib; sunitinib until progression or for a maximum of 6 months	Drug: sunitinib; oral sunitinib 37.5 mg daily; Other Names: SUTENT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
6-month progression-free survival	CT scan	every 2 months during therapy; every 3 months thereafter

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response rate	CT scan	every 2 months during therapy; every 3 months thereafter
Toxicity	outpatient visit	monthly during therapy
OVERALL SURVIVAL	outpatient visit	monthly
PROGRESSION-FREE SURVIVAL	CT scan	every 2 months during therapy; every 3 months thereafter
endothelial circulating cells		baseline + every 2 months during therapy until progression
pharmacogenomics		baseline
pharmacokynetics		after 2 months of therapy
pharmacodynamics		baseline and every 2 months until progression

Collaborators and Investigators

• Sponsor: IRCCS San Raffaele

Study record dates

Study Major Dates

• Study Start: February 1, 2008
• Primary Completion (ACTUAL): January 1, 2012
• Study Completion (ACTUAL): January 1, 2012

Study Registration Dates

• First Submitted: August 27, 2009
• First Submitted That Met QC Criteria: August 27, 2009
• First Posted (ESTIMATE): August 28, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): February 1, 2012
• Last Update Submitted That Met QC Criteria: January 31, 2012
• Last Verified: December 1, 2009

More Information

Terms related to this study

• Keywords: adenocarcinoma of the pancreas; stage IV pancreatic cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Protein Kinase Inhibitors; Sunitinib
• Other Study ID Numbers: CDR0000643632; PACT-12 (OTHER: IRCCS San Raffaele); 2008-000814-65 (EUDRACT_NUMBER)