Levorphanol for Pain in Cancer

Overseen By Akhila Reddy

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: M.D. Anderson Cancer Center

Must be taking: Strong oral opioids

Must not be taking: Methadone, Benzodiazepines

Disqualifiers: Cognitive impairment, Renal insufficiency, Hepatic insufficiency, Neuropathic pain, Substance abuse, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 10

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how well levorphanol, an opioid, can reduce cancer-related pain when other strong opioids are insufficient. Researchers aim to determine if levorphanol can better control pain in patients whose cancer may have spread. The trial involves patients currently experiencing cancer pain and already taking strong pain medications like morphine or oxycodone. Participants should be accustomed to opioids and able to visit the clinic regularly for check-ups. As an Early Phase 1 trial, this research focuses on understanding how levorphanol works in people, offering participants a chance to contribute to groundbreaking pain management solutions.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does require that you are currently being treated with strong oral opioids like morphine or oxycodone. If you are on methadone or scheduled benzodiazepines, you cannot participate in the trial.

Is there any evidence suggesting that levorphanol is likely to be safe for humans?

Research has shown that levorphanol is a safe and effective painkiller for individuals who haven't found relief with other medications. While most studies focus on non-cancer-related pain, levorphanol has also shown promise in managing cancer pain.

One study with 11 patients found that a single 2 mg dose of levorphanol reached expected blood levels without causing severe side effects. However, like other strong painkillers, levorphanol can cause serious side effects or overdose if not used correctly. Therefore, it is important to follow dosing instructions and use levorphanol under a doctor's supervision. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Levorphanol is unique because it offers a broad spectrum of pain relief by acting on multiple types of receptors in the brain, unlike many standard opioids that primarily target just one. This multi-receptor action can provide more comprehensive pain management for cancer patients, potentially reducing the need for multiple medications. Researchers are excited about levorphanol because it may offer effective pain control with fewer side effects or risk of tolerance compared to traditional opioids like morphine or oxycodone.

What evidence suggests that levorphanol might be an effective treatment for cancer pain?

Research has shown that levorphanol, a pain medication used when others aren't effective, can help control pain and symptoms in cancer patients. In one study, 8.5% of cancer patients who switched to levorphanol showed a positive response. Another study found that 40% of patients who switched from methadone to levorphanol reported excellent pain relief. Levorphanol is also generally easy for patients to tolerate, causing few side effects. These findings suggest that levorphanol can effectively manage cancer pain, especially when other pain medications are less effective. Participants in this trial will receive levorphanol as part of their supportive care regimen. ^{6 7 8 9 10}

Who Is on the Research Team?

Akhila S Reddy

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with cancer pain currently managed by strong opioids like morphine or oxycodone. They must be opioid-tolerant, local to the clinic for follow-ups, able to complete assessments, and have an ECOG status of <=3. Excluded are those with renal or hepatic insufficiency, cognitive impairment, non-English speakers, non-cancer pain sufferers, substance abuse history, methadone users, primary neuropathic pain sufferers or high sedation risk.

Inclusion Criteria

I can participate in all required study check-ups and tests.

I am used to opioids, taking 60 mg or more daily.

Individual is willing to sign written informed consent

Exclusion Criteria

Cognitive impairment with a Memorial Delirium Assessment Scale (MDAS) score of 7 or higher or diagnosed with neurocognitive impairment by the treating SCC or Pain Clinic physician

I take more than 300 mg of morphine or its equivalent daily for pain.

I am currently taking methadone.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive levorphanol orally every 8 or 12 hours for 30 days, with additional opioid regimen for breakthrough pain

4 weeks

Daily monitoring for the first 10 days, then on day 30

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension (optional)

Participants may continue levorphanol for an additional 6-8 months if determined by the Principal Investigator

6-8 months

What Are the Treatments Tested in This Trial?

Interventions

• Levorphanol

Trial Overview The study is testing levorphanol as a second line treatment for controlling cancer-related pain that may have spread in the body. It's an early phase I trial comparing levorphanol's effectiveness against other first line strong oral opioids through patient questionnaires and assessments.

How Is the Trial Designed?

Group I: Supportive care (levorphanol, opioid regimen) Experimental Treatment 7 Interventions

Patients receive levorphanol PO every 8 or 12 hours for 30 days. Patients may receive opioid regimen including hydrocodone, morphine, hydromorphone, oxycodone, and oxymorphone for breakthrough pain. Patients may continue levorphanol for an additional 6-8 months if it is determined by the Principal Investigator the patient can continue.

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36720398/

Levorphanol as a Second Line Opioid in Cancer Patients ... Conclusion: This study provided preliminary data that cancer patients could be successfully rotated to levorphanol using an ORR of 8.5.

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0885392423000477

Levorphanol as a Second Line Opioid in Cancer Patients ... Levorphanol was associated with improved pain and symptom control and was well- tolerated.

3. jpsmjournal.com jpsmjournal.com/article/S0885-3924(23)00047-7/fulltext

Levorphanol as a Second Line Opioid in Cancer Patients ... Levorphanol was associated with improved pain and symptom control and was well- tolerated.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03579446

Levorphanol as a Second Line Opioid in Reducing Pain ... This early phase I trial studies how well levorphanol works as a second line opioid in reducing pain in patients with cancer that may have spread to other ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4168847/

Levorphanol: Revisiting an Underutilized Analgesic - PMC Of the patients who were using methadone and switched to Levorphanol because of poor pain control (N = 20), 8 (40%) reported excellent relief and 7 (35%) ...

6. mayoclinic.org mayoclinic.org/drugs-supplements/levorphanol-oral-route/description/drg-20074036

Levorphanol (oral route) - Side effects & dosage Levorphanol can cause serious unwanted effects or fatal overdose if taken by children, pets, or adults who are not used to strong narcotic pain ...

7. mypcnow.org mypcnow.org/fast-fact/levorphanol/

Levorphanol Recent data suggesting it is a safe and effective opioid in patients having inadequate response to other opioids. Availability limits its use right now.

8. apm.amegroups.org apm.amegroups.org/article/view/36823/html

Levorphanol versus methadone use: safety considerations Levorphanol has been studied mostly in nonmalignant neuropathic pain syndromes, and limited data is available for cancer-related pain (1,9,10). However ...

9. pubchem.ncbi.nlm.nih.gov pubchem.ncbi.nlm.nih.gov/compound/Levorphanol

Levorphanol | C17H23NO | CID 5359272 - PubChem - NIH Levorphanol is a potent synthetic opioid analgesic indicated for the management of moderate to severe pain or as a preoperative medication where an opioid ...

10. drugs.com drugs.com/pro/levorphanol.html

Levorphanol: Package Insert / Prescribing Information One study in 11 patients using the drug for control of cancer pain reported plasma concentrations from 5 to 10 ng/mL after a single 2 mg ...