Ketorolac for Ovarian Cancer

Age: 18+

Sex: Female

Trial Phase: Academic

Sponsor: New Mexico Cancer Research Alliance

Must not be taking: NSAIDs, Anticoagulants

Disqualifiers: Non-epithelial cancer, Uncontrolled conditions, others

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 3 days

21 Participants Needed

Trial Summary

What is the purpose of this trial?

There is a move towards personalized medicine in cancer care, and significant effort is underway to evaluate new targeted therapeutics for the treatment of ovarian cancer. One way to identify potential new drug targets is by screening a drug library to determine whether drugs in the library target key kinase or enzymatic sites in cellular signaling pathways. Previous preclinical work and pilot studies demonstrated that ketorolac (a type of non-steroidal anti-inflammatory drug) inhibits GTPase activity in ovarian cancer cells retrieved from the post-operative peritoneal cavity. The purpose of this study is to confirm that this inhibitory effect is ketorolac driven and not a specific effect of the post-operative peritoneal compartment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot use ketorolac or other NSAIDs (non-steroidal anti-inflammatory drugs) within 7 days before surgery and up to the time of planned study administration.

What data supports the effectiveness of the drug Ketorolac for ovarian cancer?

Ketorolac has been shown to be an effective pain reliever in various settings, including postoperative pain and cancer pain, where it was comparable to morphine in effectiveness but with fewer side effects. This suggests it may help manage pain in ovarian cancer patients, although more specific studies are needed for this condition. ^{1 2 3 4 5}

Is ketorolac generally safe for use in humans?

Ketorolac has been used safely in humans for pain management, but it can cause side effects like gastrointestinal bleeding and kidney issues, especially in people with preexisting conditions. Most side effects are reversible after stopping the drug, and it is generally well-tolerated when used as directed. ^{4 6 7 8 9}

How does ketorolac differ from other drugs for ovarian cancer?

Ketorolac is unique for ovarian cancer treatment because it is primarily a non-steroidal anti-inflammatory drug (NSAID) typically used for pain relief, rather than a traditional chemotherapy agent. This suggests a novel approach by potentially targeting inflammation-related pathways in cancer, which is different from the standard chemotherapy drugs that directly target cancer cells. ^{10 11 12 13 14}

Research Team

Carolyn Y. Muller

Principal Investigator

University of New Mexico Comprehensive Cancer Center

Eligibility Criteria

This trial is for women over 18 with suspected or confirmed ovarian, fallopian tube, or primary peritoneal cancer who are undergoing surgery. They must be in good health otherwise, with no active bleeding, known bleeding disorders, peptic ulcers, allergies to NSAIDs like ibuprofen, and not taking other NSAIDs or anticoagulants around the time of surgery.

Inclusion Criteria

I am suspected to have ovarian, fallopian tube, or peritoneal cancer and am planning to undergo surgery to remove it.

My blood tests show enough neutrophils and platelets.

I do not have any known bleeding disorders.

Exclusion Criteria

You are allergic to NSAIDs.

My cancer is not ovarian but has spread to the ovaries.

My health conditions are stable and under control.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-3 weeks

Post-operative stabilization

Participants are monitored post-surgery until deemed stable for treatment initiation

1-3 days

Treatment

Participants receive age-based ketorolac or placebo daily for three days

3 days

Follow-up

Participants are monitored for safety, toxicity, and pharmacokinetics

4 weeks

Regular visits for toxicity and pharmacokinetics assessment

Long-term follow-up

Participants are monitored for overall survival and progression-free survival

Up to 5 years

Treatment Details

Interventions

• Ketorolac

Trial Overview The study tests if Ketorolac (a painkiller) can inhibit certain cellular activities linked to ovarian cancer growth when given after surgery. Patients will either receive Ketorolac or a placebo to see if there's a difference between the two groups.

Participant Groups

Group I: Ketorolac Experimental Treatment 1 Intervention

Once deemed stable in the first 1-3 post-operative days, patients will be receive age-based ketorolac (30 mg \<65, 15mg \> 65) daily for three days

Group II: Placebo Placebo Group 1 Intervention

Once deemed stable in the first 1-3 post-operative days, patients will be receive placebo daily for three days

Who Is Running the Clinical Trial?

New Mexico Cancer Research Alliance

Lead Sponsor

Trials

71

Recruited

52,500+

New Mexico Cancer Care Alliance

Lead Sponsor

Trials

71

Recruited

52,500+

Findings from Research

Ketorolac tromethamine is an effective nonsteroidal anti-inflammatory analgesic that can be used alone or with opiates for postoperative pain relief, showing promising results compared to morphine sulfate.

Unlike narcotic pain relievers, ketorolac does not cause respiratory depression or nausea, making it a safer option for patients, especially those with respiratory issues or those undergoing short procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketorolac tromethamine: an oral/injectable nonsteroidal anti-inflammatory for postoperative pain control. Redden, RJ.[2019]

In a study involving 176 postoperative patients, ketorolac (10 mg orally) provided analgesic efficacy comparable to both 5 mg and 10 mg doses of morphine, significantly outperforming placebo.

Ketorolac is a safe and effective option for managing acute postoperative pain, serving as a non-opioid alternative to traditional opioid therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of ketorolac in the management of postoperative pain. DeAndrade, JR., Maslanka, M., Maneatis, T., et al.[2022]

In a retrospective study of breast surgery patients over three years, ketorolac did not significantly increase the risk of postoperative hematoma formation, with rates of 3.5% in those receiving ketorolac compared to 2.5% in those who did not.

The overall hematoma rate for the entire cohort was 2.8%, suggesting that ketorolac can be safely used for postoperative pain control without raising concerns about bleeding complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toradol following Breast Surgery: Is There an Increased Risk of Hematoma? Nguyen, BN., Barta, RJ., Stewart, CE., et al.[2021]

In a study involving 51 patients with moderate to severe cancer pain, ketorolac tromethamine and morphine showed no significant difference in overall analgesic efficacy, indicating that ketorolac can be an effective alternative for pain management.

While 57% of patients on ketorolac and 74% on morphine changed their analgesic, significantly more patients discontinued ketorolac due to inadequate pain relief, whereas more patients stopped morphine due to side effects like nausea, suggesting ketorolac has a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative-study of intramuscular ketorolac tromethamine and morphine in patients experiencing cancer pain. Jameel, A., Stein, R., Rawson, N., et al.[2019]

In a multicenter study involving patients with moderate to severe inflammation after cataract surgery, ketorolac tromethamine 0.5% was significantly more effective than a placebo in reducing inflammation and associated symptoms like pain and photophobia.

The treatment was found to be safe, with no significant differences in visual acuity or adverse events compared to the placebo, indicating that ketorolac is a reliable option for managing post-surgical inflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketorolac tromethamine 0.5% ophthalmic solution in the treatment of moderate to severe ocular inflammation after cataract surgery: a randomized, vehicle-controlled clinical trial. Heier, J., Cheetham, JK., Degryse, R., et al.[2019]

Ketorolac tromethamine is an effective nonsteroidal anti-inflammatory drug (NSAID) for managing moderate to severe postoperative pain, reducing the need for opioid analgesics, which can help minimize opioid-related side effects.

Administered intramuscularly, ketorolac reaches peak plasma levels in about 45 to 50 minutes and has a low incidence of side effects, making it a promising option for both inpatient and outpatient pain management, although further research is needed to fully understand its role.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketorolac: a new parenteral nonsteroidal anti-inflammatory drug for postoperative pain management. Lassen, K., Epstein-Stiles, M., Olsson, GL.[2013]

In a case study of three patients treated with ketorolac tromethamine, two developed acute renal failure or hyperkalemia, highlighting the potential renal risks associated with this nonsteroidal anti-inflammatory drug (NSAID).

The complications were reversible in two patients after stopping the medication, emphasizing the importance of monitoring renal function in patients at risk when using ketorolac, as it can affect prostaglandin synthesis and renal vasodilation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Renal failure and hyperkalemia associated with ketorolac tromethamine. Pearce, CJ., Gonzalez, FM., Wallin, JD.[2022]

In a study involving 200 patients undergoing photorefractive keratectomy, topical ketorolac tromethamine 0.5% was found to provide significantly greater pain relief compared to its vehicle, with patients experiencing less pain intensity and a longer time before needing additional pain medication.

The ketorolac group also reported fewer side effects, such as sleep difficulties and ocular discomfort, and overall, the treatment was deemed safe with minimal adverse events, indicating its efficacy and safety for post-surgery pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analgesic efficacy and safety of ketorolac after photorefractive keratectomy. Ketorolac Study Group. Rajpal, RK., Cooperman, BB.[2022]

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]

Docetaxel has shown comparable effectiveness to paclitaxel when combined with carboplatin for treating advanced ovarian cancer, with a potentially better safety profile.

Current treatments for platinum-resistant ovarian cancer are limited, and while some experimental therapies targeting the epidermal growth factor receptor show promise, more research is needed to find effective new treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[New aspects by the therapy of ovarian cancer--What changes after the ASCO-Meeting 2001]. Costa, SD., von Minckwitz, G., Wernicke, K., et al.[2008]

Patients with recurrent ovarian cancer are categorized as either platinum-sensitive or platinum-resistant, which influences treatment options; platinum-sensitive patients often benefit from re-treatment with paclitaxel/platinum combinations, while platinum-resistant patients may receive single-agent therapies like altretamine or topotecan.

For platinum-sensitive patients with minimal residual disease, intensive intraperitoneal therapy with cisplatin and paclitaxel shows the most promise for long-term disease-free survival, highlighting the importance of tailored treatment strategies based on disease characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of refractory and recurrent ovarian cancer. Alberts, DS.[2005]

References

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

Ketorolac tromethamine: an oral/injectable nonsteroidal anti-inflammatory for postoperative pain control. [2019]

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

The use of ketorolac in the management of postoperative pain. [2022]

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

Toradol following Breast Surgery: Is There an Increased Risk of Hematoma? [2021]

4. Greece pubmed.ncbi.nlm.nih.gov

Comparative-study of intramuscular ketorolac tromethamine and morphine in patients experiencing cancer pain. [2019]

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

Ketorolac tromethamine 0.5% ophthalmic solution in the treatment of moderate to severe ocular inflammation after cataract surgery: a randomized, vehicle-controlled clinical trial. [2019]

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

Ketorolac: a new parenteral nonsteroidal anti-inflammatory drug for postoperative pain management. [2013]

7. England pubmed.ncbi.nlm.nih.gov

Use of ketorolac by continuous subcutaneous infusion for the control of cancer-related pain. [2019]

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

Renal failure and hyperkalemia associated with ketorolac tromethamine. [2022]

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

Analgesic efficacy and safety of ketorolac after photorefractive keratectomy. Ketorolac Study Group. [2022]

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

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

11. Germany pubmed.ncbi.nlm.nih.gov

[New aspects by the therapy of ovarian cancer--What changes after the ASCO-Meeting 2001]. [2008]

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

Treatment of refractory and recurrent ovarian cancer. [2005]

13. England pubmed.ncbi.nlm.nih.gov

Phase II study of the combination carboplatin plus celecoxib in heavily pre-treated recurrent ovarian cancer patients. [2021]

14. England pubmed.ncbi.nlm.nih.gov

Microenvironmental effects limit efficacy of thymoquinone treatment in a mouse model of ovarian cancer. [2018]