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

Trial Summary

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 data supports the effectiveness of the drug hydromorphone for pain relief in gynecologic cancer?

Research shows that hydromorphone is effective for managing moderate to severe cancer pain, similar to other opioids like morphine and oxycodone. It is well-tolerated and can help reduce the need for additional pain medication. ^{1 2 3 4 5}

Is hydromorphone safe for cancer pain management?

Hydromorphone has been shown to be generally safe for managing cancer pain, with common side effects including nausea, vomiting, constipation, drowsiness, and dry mouth. No severe adverse effects were observed in studies, and it is considered a tolerable alternative to other opioids like morphine and oxycodone. ^{2 5 6 7 8}

How does the drug Methadone differ from other drugs for gynecologic cancer pain relief?

Methadone and Hydromorphone are unique in their use for pain relief in gynecologic cancer because they are opioids, which work by changing how the brain and nervous system respond to pain. This is different from other treatments like chemotherapy, which target cancer cells directly. ^{9 10 11 12 13}

What is the purpose of this trial?

This phase IV trial compares methadone versus hydromorphone given in the fluid-filled space between the thin layers of tissue that cover the brain and spinal cord (intrathecal) for postoperative pain relief in patients with gynecologic cancer undergo surgery. Methadone binds to opioid receptors in the central nervous system and is a long-acting opioid pain medication. Intrathecal hydromorphone works by changing the way the brain and nervous system respond to pain and is similar to an epidural. This trial may help researchers determine if methadone works as well as intrathecal hydromorphone for pain relief after surgery in patients with gynecologic cancer.

Research Team

Sean C. Dowdy, M.D.

Principal Investigator

Mayo Clinic in Rochester

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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 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]

References

1. United States 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. [2013]

2. England pubmed.ncbi.nlm.nih.gov

The role of hydromorphone in cancer pain treatment: a systematic review. [2018]

3. England pubmed.ncbi.nlm.nih.gov

Hydromorphone for cancer pain. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

The role of OROS hydromorphone in the management of cancer pain. [2013]

5. Japan pubmed.ncbi.nlm.nih.gov

[Hydromorphone in Cancer Patients-A Retrospective Study]. [2020]

6. United States 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. [2012]

7. United States 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. [2022]

8. United States 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. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Platinum compounds in cervical and endometrial cancers: focus on carboplatin. [2013]

10. United States pubmed.ncbi.nlm.nih.gov

Chemotherapy for advanced or recurrent gynecologic cancer. [2019]

11. United States pubmed.ncbi.nlm.nih.gov

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

12. Korea (South) pubmed.ncbi.nlm.nih.gov

The influence of hormone therapy with drospirenone-estradiol on endometrioid type endometrial cancer patients. [2019]

13. Japan pubmed.ncbi.nlm.nih.gov

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