Oxcarbazepine Plus Morphine in Patients With Refractory Cancer Pain

A Phase Ib Study of Oxcarbazepine Plus Morphine in Patients With Refractory Cancer Pain

This is an open-label, single arm, Phase Ib dose escalation study of Oxcarbazepine with morphine in patients with refractory cancer pain. The primary endpoint is to evaluate the safety and toxicity of the combination of Oxcarbazepine plus morphine. The secondary endpoints are improving pain control, reduce morphine use and improve the quality of life.

Study Overview

• Status: Terminated
• Conditions: Cancer
• Intervention / Treatment: Drug: Morphine; Drug: Oxcarbazepine

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Simon Cancer Center
    • Indianapolis, Indiana, United States, 46202
      • Indiana Univeristy Health Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Written informed consent and HIPAA authorization for release of personal health information.

  •≥ 18 years old at the time of informed consent

• Patients with histologically confirmed diagnosis of cancer NOTE: Patients with active cancer or post treatment are allowed on the study.
• Patients must be receiving stable or increasing doses of morphine for 1-2 weeks prior to registration for protocol therapy.

NOTE: Switching patient from current pain regimen to morphine equivalent for at least 1-2 weeks prior to registration for protocol therapy is required.

• Requiring greater than or equal to 180 mg of morphine per day. See Appendix 1 for Morphine Conversion Calculator.
• Inadequately controlled pain even with the use of morphine (VAS score >5) See Appendix 8
• Rescue pain medications are allowed this may include the use of NSAIDS or Tylenol as well as morphine IR.
• ECOG Performance Status of 0-2
• Ability to swallow and tolerate oral tablets.
• Patients getting radiation therapy are allowed at the discretion of the treating physician.
• Females of childbearing potential must have a negative pregnancy test NOTE: Females are considered of child bearing potential unless they are surgically sterile (they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are postmenopausal (> 12 months since last menses).

NOTE: Females using hormonal contraceptives should be switched to non-hormonal forms of contraception.

The following laboratory values must be obtained. Patient with aplastic anemia will be excluded.

• White blood cell count (WBC) ≥ 3.0 K/mm3
• Absolute neutrophil count ≥ 1.5 K/mm3
• Hemoglobin (Hgb) ≥ 9 g/dL
• Platelets ≥ 75 K/mm3
• Creatinine ≤ 1.5 mg/dl
• Bilirubin ≤ 1.5 x ULN
• Aspartate aminotransferase (AST, SGOT) ≤ 3 x ULN
• Alanine aminotransferase (ALT, SGPT) ≤ 3 x ULN

Exclusion Criteria:

• Active central nervous system (CNS) metastases. Patients with neurological symptoms should undergo a head CT scan or brain MRI to exclude brain metastasis, at the discretion of the treating physician.

NOTE: Patients with prior brain metastasis may be considered if they have completed their treatment for brain metastasis, no longer require corticosteroids, and are asymptomatic.

• Concurrent use of adjuvant medication such as but not limited to: gabapentin, pregabalin or duloxetine etc.

NOTE: Patients on gabapentin or pregabalin can be considered if they can be tapered off before enrolling on the study.

• Treatment with any investigational agent within 30 days prior to registration for protocol therapy.
• Patient with rapidly escalating pain that require hospitalization or an intravenous opioid therapy
• Concurrent participation in a clinical trial which involves another investigational agent.
• Concurrent use of medications that are strong CYP3A4 inhibitors within 14 days prior to registration for protocol therapy as Oxcarbazepine is strong CYP3A4 inducer. See Appendix 7.

NOTE: Concurrent use of other CYP3A4 inhibitors may be allowed at the discretion of the treating physician or principal investigator.

• Allergic reaction to carbamazepine or oxcarbazepine (HLA-B1502)
• Allergy or other contraindication to morphine sulphate
• Opiate-induced uncontrolled constipation or bowel obstruction
• Patient who lives alone.
• Female who is pregnant or breastfeeding
• Patient who has a diagnosis of epilepsy and/or is currently taking anti-epileptic drugs

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Oxcarbazepine and Morphine; Patients must be on stable or increasing doses of greater than or equal to 180 mg of morphine sulfate per day. Morphine is taken orally for 42 days. In addition to Morphine, patients will also receive oral Oxcarbazepine 150 mg, every 12 hours, for 2 weeks, then increase the dose to 300 mg, every 12 hours, for 2 weeks and then increase the dose to 450 mg, every 12 hours, for the final 2 weeks. Patients will take oral tablets of oxcarbazepine for a total of 42 days.

Drug: Morphine; Morphine will be given to patients as part of their standard care; Other Names: Morphine Sulfate; Drug: Oxcarbazepine; Can be taken with or without food at the same time as morphine. Morphine will be provided to patients free of charge.; Other Names: Tileptal

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with adverse events as a measure of safety and toxicity	Evaluate the safety and toxicity of oxcarbazepine in combination with morphine	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Pain control	Evaluate changes in pain control after adding oxcarbazepine to morphine	1 year
Changes in Consumption	Evaluate changes morphine consumption after adding oxcarbazepine to morphine	1 year
Changes in Quality of Life	Evaluate changes in Quality of Life after adding oxcarbazepine to morphine	1 year

Collaborators and Investigators

• Sponsor: Costantine Albany
• Investigators: Principal Investigator: Costantine Albany, M.D., Indiana University

Study record dates

Study Major Dates

• Study Start (Actual): March 6, 2014
• Primary Completion (Actual): December 11, 2014
• Study Completion (Actual): December 11, 2014

Study Registration Dates

• First Submitted: February 24, 2014
• First Submitted That Met QC Criteria: March 3, 2014
• First Posted (Estimate): March 5, 2014

Study Record Updates

• Last Update Posted (Estimate): January 31, 2017
• Last Update Submitted That Met QC Criteria: January 27, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: Refractory cancer pain
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Cancer Pain; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Membrane Transport Modulators; Anticonvulsants; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Morphine; Oxcarbazepine
• Other Study ID Numbers: IUCRO-0453

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No