Methadone vs Hydromorphone for Pain Relief in Gynecologic Cancer

Overseen By Karen Ishitani, R.N.

Age: Any Age

Sex: Female

Trial Phase: Phase 4

Sponsor: Mayo Clinic

Must not be taking: Opioids, Anticoagulants

Disqualifiers: Chronic pain, Kidney disease, Cirrhosis, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

Duration: 1 day

140 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether methadone provides pain relief as effectively as hydromorphone after surgery in patients with gynecologic cancer. Methadone is a long-lasting pain medication that affects the central nervous system, while hydromorphone (also known as Dilaudid or Exalgo) alters the brain's response to pain. Participants will receive one of these medications during surgery to determine which offers better pain management. The trial seeks patients undergoing surgery for gynecologic cancer who will remain in the hospital for more than 24 hours. As a Phase 4 trial, this research aims to understand how these FDA-approved treatments benefit a broader patient population.

Do I need to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on chronic pain medications or anticoagulation medications, you may need to discuss this with the trial team.

What is the safety track record for these treatments?

Research shows that methadone is generally well-tolerated for managing cancer pain, providing good pain relief with manageable side effects. Methadone acts as a strong painkiller, similar to other opioids, for cancer patients, suggesting it is relatively safe during cancer treatment.

Research also supports the safety of hydromorphone for pain management in cancer patients. It has proven effective and safe, offering pain relief comparable to other common opioids like oxycodone and morphine. Patients using hydromorphone report similar pain relief without unexpected side effects.

Both methadone and hydromorphone help manage pain in cancer patients. They have long-standing use and well-established safety records, having been studied and used in many patients, indicating general safety when used as directed. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these treatments, methadone and hydromorphone, for pain relief in gynecologic cancer because they offer unique approaches compared to typical opioid options. Methadone is distinctive because it has a dual action mechanism, acting both as a pain reliever and an NMDA receptor antagonist, which may help manage pain more effectively and reduce the risk of opioid tolerance. On the other hand, hydromorphone administered intrathecally (IT) allows for direct spinal delivery, providing targeted pain relief with potentially lower doses and fewer systemic side effects. These innovative strategies could offer more effective and safer pain management options for patients undergoing surgery.

What evidence suggests that this trial's treatments could be effective for pain relief in gynecologic cancer?

This trial will compare methadone and hydromorphone for pain relief in patients with gynecologic cancer. Research has shown that methadone, which participants in this trial may receive, effectively relieves pain in cancer patients with few side effects. In one study, 90% of patients taking methadone reported relief from nerve-related pain. Methadone is also known for its long-lasting effects, which can help manage pain over time.

Hydromorphone, another treatment option in this trial, has proven effective in reducing pain in cancer patients. Studies have found it to be as effective as other painkillers like morphine and oxycodone. Most patients using hydromorphone also experience good pain relief. Both methadone and hydromorphone are strong options for managing pain after surgery in patients with gynecologic cancer. ^{1 2 3 6 7}

Who Is on the Research Team?

Sean C. Dowdy, M.D.

Principal Investigator

Mayo Clinic in Rochester

Are You a Good Fit for This Trial?

This trial is for patients with gynecologic cancer who are undergoing surgery and need postoperative pain relief. The specific eligibility criteria aren't provided, but typically participants must meet certain health standards and not have conditions that would exclude them from safely receiving the interventions.

Inclusion Criteria

I will be admitted to the hospital for more than a day.

I am having surgery through an abdominal cut for a female reproductive cancer.

Exclusion Criteria

Intolerance to hydromorphone or methadone

I cannot take liposomal bupivacaine due to health reasons.

I have had surgeries after my first major cancer surgery.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive either methadone intravenously or hydromorphone intrathecally during induction of general anesthesia for surgery

1 day

1 visit (in-person)

Postoperative Monitoring

Patients are monitored for pain relief and side effects such as itching and respiratory depression

24 hours

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Hydromorphone
• Methadone

Trial Overview The study compares two pain relief methods after surgery: methadone (a long-acting opioid) versus intrathecal hydromorphone (similar to an epidural). It aims to determine which drug provides better postoperative pain management for these patients.

How Is the Trial Designed?

Group I: Arm II (hydromorphone) Experimental Treatment 2 Interventions

Patients receive hydromorphone IT prior to induction of general anesthesia for SOC surgery.

Group II: Arm I (methadone) Experimental Treatment 2 Interventions

Patients receive methadone IV during induction of general anesthesia for SOC surgery.

Hydromorphone is already approved in United States, Canada, European Union for the following indications:

Approved in United States as Dilaudid for:

• Moderate to severe pain

Approved in Canada as Hydromorphone for:

• Moderate to severe pain

Approved in European Union as Hydromorphone for:

• Moderate to severe pain

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Published Research Related to This Trial

Cisplatin remains the primary drug for systemic therapy in cervical cancer, but there is ongoing evaluation of carboplatin as a potential substitute, especially for elderly patients, due to its reproducible activity and compatibility with radiation therapy.

Current studies suggest that while cisplatin is effective, carboplatin may offer a viable alternative in certain cases, particularly for palliative care, indicating the need for further research into its efficacy compared to cisplatin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Platinum compounds in cervical and endometrial cancers: focus on carboplatin. Muggia, FM., Muderspach, L.[2013]

Hydromorphone is effective and tolerable for managing moderate to severe cancer pain, based on a systematic review of 13 studies involving 1208 patients, but it does not show clear superiority over morphine or oxycodone.

The studies indicated that while hydromorphone and morphine provide similar pain relief, side effects varied slightly but were not consistent, suggesting that hydromorphone can be a viable alternative to traditional opioids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of hydromorphone in cancer pain treatment: a systematic review. Pigni, A., Brunelli, C., Caraceni, A.[2018]

In a multicenter study involving 114 patients with chronic cancer pain, switching to once-daily OROS® hydromorphone significantly reduced the frequency of breakthrough pain (BTP) medication from 2.93 to 2.00 by day 14, indicating its effectiveness in managing pain.

Despite common side effects like constipation and dizziness occurring in 91.2% of patients, a majority (61.2%) reported satisfaction with the treatment, suggesting that OROS® hydromorphone is a viable option for controlling cancer pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical effectiveness and safety of OROS® hydromorphone in break-through cancer pain treatment: a multicenter, prospective, open-label study in Korean patients. Lee, KH., Kim, MK., Hyun, MS., et al.[2013]

A systematic review of 8 studies involving 1283 participants found that hydromorphone does not show clear evidence of being more effective than other opioids like oxycodone or morphine for relieving cancer pain, indicating uncertainty in its analgesic efficacy.

The review also highlighted that while hydromorphone was associated with some adverse events such as nausea and constipation, there was no significant difference in these side effects compared to other opioids, suggesting a need for further research to clarify its safety and effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hydromorphone for cancer pain. Li, Y., Ma, J., Lu, G., et al.[2023]

In a study of 58 women with early-stage endometrial cancer who received postoperative hormone therapy with drospirenone/estradiol (DRSP/E2), there was no significant increase in disease recurrence or overall mortality compared to a control group of 116 women who did not receive the treatment.

The study found that while the median tumor diameter was larger in the DRSP/E2 group, factors such as disease-free survival and overall survival rates were not significantly different between the two groups, suggesting that DRSP/E2 is safe for use in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The influence of hormone therapy with drospirenone-estradiol on endometrioid type endometrial cancer patients. Lim, S., Kim, YH., Lee, KB., et al.[2019]

In a pooled analysis of 11 studies involving 1251 opioid-tolerant patients, once-daily OROS hydromorphone ER showed a safety profile consistent with known opioid safety, with a high incidence of adverse events (76.9%), including nausea (23.2%) and constipation (22.4%).

Despite the high incidence of adverse events, no treatment-related deaths were reported, indicating that OROS hydromorphone ER can be a tolerable option for managing chronic pain in opioid-tolerant patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Tolerability of Once-Daily OROS(®) hydromorphone extended-release in opioid-tolerant adults with moderate-to-severe chronic cancer and noncancer pain: pooled analysis of 11 clinical studies. Nalamachu, SR., Kutch, M., Hale, ME.[2012]

In a study of 19 cancer patients, switching to oral hydromorphone for pain management was feasible and did not result in significant changes in pain levels, with average pain scores slightly decreasing from 4.1 to 3.8 after the switch.

No severe adverse effects were reported, and the extended-release formulation of hydromorphone was well-received due to its ease of administration, suggesting it is a safe and practical option for managing cancer pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Hydromorphone in Cancer Patients-A Retrospective Study]. Sato, N., Satomi, E., Yoshida, T., et al.[2020]

A systematic review of 25 studies on opioid use for cancer-related pain revealed a wide range of adverse event (AE) rates, with nausea reported between 3% and 85% and constipation between 5% and 97%, highlighting significant variability in patient experiences.

The review emphasizes that due to the heterogeneity in how AEs are assessed and reported across studies, realistic incidence rates for opioid-related AEs remain unclear, indicating a need for standardized measures in future research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Systematic Review of Prospective Studies Reporting Adverse Events of Commonly Used Opioids for Cancer-Related Pain: A Call for the Use of Standardized Outcome Measures. Oosten, AW., Oldenmenger, WH., Mathijssen, RH., et al.[2022]

A study involving 44 patients with stable cancer pain found that controlled-release oxycodone, administered every 12 hours, provided similar pain relief and safety compared to controlled-release hydromorphone, which also was given every 12 hours.

Controlled-release oxycodone showed a favorable safety profile, with no reported hallucinations, while two patients experienced hallucinations with hydromorphone, highlighting oxycodone as a promising option for managing cancer pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative clinical efficacy and safety of a novel controlled-release oxycodone formulation and controlled-release hydromorphone in the treatment of cancer pain. Hagen, NA., Babul, N.[2022]

The once-daily sustained-release formulation of hydromorphone (OROS hydromorphone) provides consistent pain management for cancer patients by maintaining stable opioid plasma levels, which reduces the need for rescue medications for breakthrough pain.

Clinical studies indicate that OROS hydromorphone has a good safety profile and offers comparable efficacy to other opioids like morphine and oxycodone, making it a promising option for cancer pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of OROS hydromorphone in the management of cancer pain. Gardner-Nix, J., Mercadante, S.[2013]

Cisplatin-based combination chemotherapy has shown a significant improvement in response rates for advanced gynecologic cancers, particularly ovarian cancer, but has not demonstrated a clear survival advantage over lower-dose combinations with alkylating agents.

Cisplatin remains the most effective single agent for squamous cell carcinoma of the cervix, and while other agents have shown moderate activity, no combination therapy has outperformed cisplatin alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy for advanced or recurrent gynecologic cancer. Thigpen, T., Vance, R., Lambuth, B., et al.[2019]

In vitro studies showed that HOC-21 ovarian adenocarcinoma cells were particularly sensitive to Cis-platinum, Adriamycin, and actinomycin-D, suggesting these drugs may be effective treatments for this type of cancer.

HEC-1B endometrial adenocarcinoma cells responded well to progesterone, while SKG-1 cervical squamous cell carcinoma cells were more sensitive to bleomycin and mitomycin-C, indicating that different gynecologic tumors may require tailored drug therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effect of anticancer drugs on in vitro survival of cell lines derived from various gynecologic tumors (author's transl)]. Sekiya, S., Takamizawa, H.[2006]

Docetaxel combined with carboplatin is a feasible and tolerable first-line treatment option for newly diagnosed epithelial ovarian cancer, showing no significant difference in progression-free or overall survival compared to the traditional paclitaxel and carboplatin combination in a study of 1,077 patients.

While docetaxel was associated with more myelosuppression, it resulted in fewer cases of neuropathy compared to paclitaxel, leading to better quality-of-life outcomes for patients receiving docetaxel.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of docetaxel in the treatment of newly diagnosed advanced ovarian cancer. Vasey, PA.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6457981/

Hydromorphone for cancer pain - PMC - PubMed Central - NIH Based on very low quality evidence, we found no differences between the treatment groups relating to pain intensity and most people had good pain relief.

2. sciencedirect.com sciencedirect.com/science/article/pii/S1526590014007202

Safety and Efficacy of Once-Daily Hydromorphone ... Beneficial reduction in pain severity with hydromorphone ER has been noted in moderate to severe cancer pain patients with all types of cancers, for treatment ...

3. bmcanesthesiol.biomedcentral.com bmcanesthesiol.biomedcentral.com/articles/10.1186/s12871-024-02638-y

Efficacy and safety of hydromorphone for cancer pain Hydromorphone demonstrated efficacy similar to that of morphine and oxycodone in reducing cancer pain intensity, decreasing additional analgesic consumption, ...

4. jgo.amegroups.org jgo.amegroups.org/article/view/92179/html

Patient-controlled analgesia with hydromorphone treatment ... Zeng et al. (8) found that PCA with hydromorphone and morphine can effectively and safely relieve short-term moderate-to-severe cancer pain.

5. cancer.org cancer.org/cancer/managing-cancer/side-effects/pain/cancer-pain/opioid-pain-medicines-for-cancer-pain.html

Opioids for Cancer Pain | Treatment and Side Effects Opioids are used to treat moderate to severe cancer pain. They are often a part of a pain relief plan for cancer patients. Learn more here.

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2010/021217s000MedR.pdf

21-217s000 - accessdata.fda.gov The safety data from this study was reviewed in the original NDA for Dilaudid CR. That review, however, was of an interim study report (dated October 12 ...

7. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2717556

Opioid Protocol for Pain Management After Gynecologic ... This case-control cohort study compares the total number of opioid pain medications prescribed after gynecologic and abdominal surgery, ...