Official Title: “A Randomized Study of Optimal Pain Management: Standard Pain Control Versus Early Intervention With Intrathecal Therapy in Patients With Advanced Pancreatic Cancer”

RATIONALE: Giving medications in different ways may change their effectiveness in controlling pain. It is not yet known whether intrathecal therapy is more effective than standard therapy in controlling pain in patients with pancreatic cancer.

PURPOSE: This randomized clinical trial is studying standard pain control to see how well it works compared with intrathecal therapy in controlling pain in patients with locally advanced, unresectable, or metastatic pancreatic cancer.

Study Type: Interventional

Study Design: Supportive Care, Randomized, Open Label

Study Primary Completion Date: December 2010

OBJECTIVES:

Primary - To compare the effectiveness of pain control comprising intrathecal opioid delivery versus the standard analgesia-delivery method in patients with locally advanced, unresectable, or metastatic pancreatic cancer.

Secondary - To assess the difference of a total amount of opioid consumption (parenteral morphine equivalent) between two different opioids-delivery groups at one month of treatment. - To assess the average of percent change in Karnofsky performance status with respect to the baseline status between two different analgesic-delivery groups at one month of treatment. - To assess the difference in quality of life between two different opioids-delivery groups at one month of treatment using the EORTC QLQ-C30. - To assess overall survival of these patients. - To assess the safety profile of two different analgesic-delivery methods (i.e., adverse event and serious adverse event).

OUTLINE: Patients are stratified according to Karnofsky performance status (60-80% vs > 80%).

Patients are randomized to 1 of 2 treatment arms. - Arm I (standard pain management): Patients are evaluated by the JHH Pain Medicine Integrated Team for pain, for the potential of diagnostic/neurolytic celiac plexus block, and undergo the institution of or modification of or continuation and titration of oral or parenteral analgesics. Patients undergo a limited, problem-oriented physical exam including weight, vital signs, Karnofsky performance status (KPS), assessment of previously abnormal findings or new complaints, pain scores, analgesia consumption, side effects (i.e., sleepiness, nausea, pruritus, and constipation), and quality-of-life score (EORTC QLQ-C30) once every 2 weeks for 3 months and then once a month thereafter.

Patients also keep a diary of pain scores and side effects during the trial. Patients may have their treatment titrated as needed to control their pain. Patients who are not adequately pain controlled or develop debilitating side effects from their therapy may be managed by adjuvant analgesics or be allowed to crossover into the treatment arm of the study to provide compassionate care. - Arm II (intrathecal therapy): Patients undergo implantation of a Medtronic intrathecal pump and catheter system for delivery of morphine sulfate directly into the spinal fluid as well as clonidine and/or bupivacaine hydrochloride as adjuvants at the discretion of the investigating clinician. Following implantation, patients undergo a limited, problem-oriented physical exam including vital signs, KPS, assessment of previously abnormal findings or new complaints, pain scores, analgesia consumption, and quality-of life-score (EORTC QLQ-C30) once every 2 weeks for 3 months and then once a month thereafter. Patients are also evaluated by the Interventional Pain Treatment Team for wound status, presence of symptoms of post-dural puncture headache, signs of infection, or meningitis. Patients are followed by the JHH Pain Medicine Integrated Team for evaluation of pain and for institution of or modification of or continuation and titration of oral or parenteral analgesics.

After completion of study treatment, patients are followed for 1 year.

Intervention(s) in this Clinical Trial

• Drug: bupivacaine hydrochloride
• Drug: clonidine
• Drug: morphine sulfate
• Procedure: assessment of therapy complications
• Procedure: quality-of-life assessment

Primary Measures

• Pain as verbally reported by the patient on a 0-10 verbal scale
  • Safety Issue?: No

Secondary Measures

• Clinical benefit response as measured by change in analgesic consumption (PME), Karnofsky performance status, and quality-of-life scores (EORTC QLQ-C30)
  • Safety Issue?: No
• Side effects (i.e., nausea, sedation, pruritus, constipation, respiratory depression, and urinary retention)
  • Safety Issue?: Yes
• Patient survival
  • Safety Issue?: No
• Safety
  • Safety Issue?: Yes

DISEASE CHARACTERISTICS:

Inclusion criteria:

• Histologically confirmed adenocarcinoma of the pancreas
• Mixed adenocarcinoma tumors allowed provided the predominant invasive component of the tumor is adenocarcinoma
• Locally advanced, unresectable, or metastatic disease
• Patients must be within two months of diagnosis or have started chemotherapy within 60 days of study
• Average pain score ≥ 4/10 over a 7-day period on a verbal numerical rating scale

Exclusion criteria:

• Known brain metastases
• Tumor with clinically significant obstruction of the spinal canal

PATIENT CHARACTERISTICS:

Inclusion criteria:

• Karnofsky performance status 60-100%
• ANC ≥ 1,500 cells/mm³
• Hematocrit ≥ 28%
• WBC ≥ 3,500 cells/mm³
• Platelets ≥ 90,000/mm³
• Serum creatinine ≤ 2.0 mg/dL
• Bilirubin ≤ 2.5 mg/dL
• AST/ALT ≤ 5 times upper limit of normal (ULN)
• Alkaline phosphatase ≤ 5 times ULN
• INR ≤ 1.5
• Not pregnant or nursing
• Negative pregnancy test
• Mini-mental status exam score ≥ 22

Exclusion criteria:

• Uncontrolled medical conditions that could potentially increase the risk of toxicities or complications of this therapy, including any of the following:
• Gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation
• Active peptic ulcer disease
• Active infections
• Insensitive to opioid medication for cancer pain
• Insufficient tissue or decubitus ulcer near device implantation site
• Current history of substance abuse

PRIOR CONCURRENT THERAPY:

• Minor procedures (i.e., dental work or skin biopsy), tumor biopsies, and biliary stent placement are allowed
• No prior surgical procedures affecting absorption
• Prior or other concurrent pain medications are allowed
• Concurrent chemotherapy or radiotherapy allowed at the discretion of the treating physician

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Sidney Kimmel Comprehensive Cancer Center

Overall Clinical Trial Officials and Contacts

Michael Erdek, MD Principal Investigator Sidney Kimmel Comprehensive Cancer Center  

Information obtained from ClinicalTrials.gov on August 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00660348

Study ID Number: CDR0000593173

ClinicalTrials.gov Identifier: NCT00660348

Health Authority: Unspecified

Clinical trial summary from the National Cancer Institute's PDQ® database