Dexamethasone for Advanced Cancer

Recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Megestrol, Oral corticosteroids

Disqualifiers: Diabetes, HIV, Anemia, Neutropenia, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 4 weeks

132 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this clinical research study is to learn if dexamethasone can help to control symptoms such as fatigue, pain, nausea, weight loss, loss of appetite, sleep problems, and/or depression in patients with advanced cancer.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot participate if you are currently taking Megestrol and haven't stopped it for more than 7 days. Also, you cannot be on oral corticosteroids for more than 7 days before joining the study.

What data supports the effectiveness of the drug Dexamethasone for advanced cancer?

Dexamethasone is commonly used in advanced cancer patients to help with symptoms like appetite loss, nausea, and fatigue, with positive effects seen within the first week and lasting beyond four weeks. It is also used in combination with other treatments, like docetaxel, to enhance their effectiveness in certain cancers, such as prostate cancer. ^{1 2 3 4 5}

Is dexamethasone generally safe for humans?

Dexamethasone is used in various treatments, but it can cause side effects like neuro-psychiatric issues (mental health problems) and myopathy (muscle weakness), especially in children with leukemia. It is generally well-tolerated in combination with other drugs for multiple myeloma, but its safety can vary depending on the condition and patient. ^{3 6 7 8 9}

How is the drug Dexamethasone unique in treating advanced cancer?

Dexamethasone is unique in treating advanced cancer because it is a corticosteroid that not only helps manage cancer pain and side effects like nausea but also has the potential to enhance the effectiveness of other cancer treatments, such as docetaxel, by reducing inflammation and inhibiting tumor growth. ^{1 2 4 10 11}

Research Team

Sriram Yennurajalingam, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for adults with advanced cancer experiencing at least three symptoms like pain, fatigue, or nausea. They must have a life expectancy of 30 days or more and not be candidates for aggressive cancer therapy. People with allergies to Dexamethasone, anemia, HIV, diabetes, recent major surgery, ongoing infections or those on certain medications are excluded.

Inclusion Criteria

No clinical evidence of cognitive failure as evidenced by Memorial Delirium Assessment Scale (MDAS) score of 13 or less at baseline

Life expectancy =/> 30 days

I am using topical or inhaled steroids, or have used oral steroids for 7 days or less.

Exclusion Criteria

Inability to complete the baseline assessment forms

Patients with a history of diabetes will be excluded

I do not have sepsis or any current infections.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either dexamethasone or placebo for 14 days, followed by dexamethasone for another 14 days with dose tapering

4 weeks

4 visits (in-person or phone)

Follow-up

Participants are monitored for safety and toxicity after treatment

2 weeks

1 visit (in-person or phone)

Treatment Details

Interventions

• Dexamethasone
• Placebo

Trial Overview The study is testing whether Dexamethasone can alleviate symptoms such as fatigue, pain and nausea in patients with advanced solid tumors. Participants will either receive Dexamethasone or a placebo to compare the effectiveness in symptom control.

Participant Groups

Group I: Dexamethasone Active Control 1 Intervention

Dexamethasone 4 mg orally two times a day for 14 days. On day 15 \[ ± 3 days\], all patients receive dexamethasone 4 mg orally twice a day for 7 days, and then the dose of dexamethasone tapered to 2 mg orally twice a day between days 22 to 28.

Group II: Placebo Placebo Group 2 Interventions

Placebo by mouth (PO) twice daily for 14 days. On day 15 \[ ± 3 days\], all patients receive dexamethasone 4 mg orally twice a day for 7 days, and then the dose of dexamethasone tapered to 2 mg orally twice a day between days 22 to 28.

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

Approved in European Union as Dexamethasone for:

• Inflammation
• Allergic reactions
• Respiratory diseases
• Skin conditions
• Eye diseases
• Immune system disorders

Approved in United States as Dexamethasone for:

• Inflammatory conditions
• Allergic states
• Respiratory diseases
• Blood disorders
• Neoplastic diseases
• Nervous system disorders

Approved in Canada as Dexamethasone for:

• Inflammation
• Allergic reactions
• Respiratory diseases
• Skin conditions
• Eye diseases

Approved in Japan as Dexamethasone for:

• Inflammatory conditions
• Allergic states
• Respiratory diseases
• Blood disorders

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

American Cancer Society, Inc.

Collaborator

Trials

237

Recruited

110,000+

Findings from Research

In a study of 254 advanced non-squamous NSCLC patients, prophylactic dexamethasone did not significantly affect progression-free survival (PFS) or overall survival when used alongside PD-1 blockade therapy and chemotherapy.

The use of dexamethasone for preventing chemotherapy-associated adverse events (CAAEs) was found to be safe, as it did not lead to increased immune-related adverse effects (irAEs) or negatively impact clinical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of prophylactic dexamethasone on the efficacy of immune checkpoint inhibitors plus platinum-based chemotherapy in patients with advanced Non-Squamous Non-Small-Cell lung cancer. Yu, H., Chen, J., Zhou, Y., et al.[2023]

In a study involving 1603 children with newly diagnosed acute lymphoblastic leukaemia (ALL), substituting dexamethasone for prednisolone significantly reduced the risk of isolated central nervous system (CNS) relapse by half.

Dexamethasone treatment improved event-free survival rates to 84.2% compared to 75.6% with prednisolone over 5 years, indicating that despite its increased toxicity, dexamethasone should be considered a standard part of therapy for childhood ALL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Benefit of dexamethasone compared with prednisolone for childhood acute lymphoblastic leukaemia: results of the UK Medical Research Council ALL97 randomized trial. Mitchell, CD., Richards, SM., Kinsey, SE., et al.[2022]

Dexamethasone (DEX) is more effective than prednisone (PRED) in reducing the risk of serious events in children with acute lymphoblastic leukemia (ALL), including central nervous system relapse, based on a meta-analysis of eight studies.

However, DEX is associated with a higher risk of severe side effects, such as increased mortality during induction therapy and neuro-psychiatric issues, raising concerns about its overall safety despite its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dexamethasone versus prednisone for induction therapy in childhood acute lymphoblastic leukemia: a systematic review and meta-analysis. Teuffel, O., Kuster, SP., Hunger, SP., et al.[2018]

Dexamethasone, while effective for treating pediatric acute lymphoblastic leukemia (ALL), can cause significant neurobehavioral side effects that negatively impact health-related quality of life (HRQoL) in patients, as identified through the Strengths and Difficulties Questionnaire (SDQ).

The current study aims to replicate previous findings that adding physiological hydrocortisone during dexamethasone treatment may alleviate these neurobehavioral issues, with a randomized controlled trial design to assess changes in SDQ scores and other quality of life measures in affected patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study protocol: DexaDays-2, hydrocortisone for treatment of dexamethasone-induced neurobehavioral side effects in pediatric leukemia patients: a double-blind placebo controlled randomized intervention study with cross-over design. van Hulst, AM., Verwaaijen, EJ., Fiocco, MF., et al.[2021]

Adolescents with Acute Lymphoblastic Leukaemia (ALL) experience more severe adverse drug reactions (ADRs) from oral dexamethasone compared to younger children, with higher incidences of issues like hyperglycemia, infections, and thrombosis, based on a review of 11 studies.

The increased severity of ADRs in adolescents may be linked to age-related differences in how dexamethasone is processed in the body and the effects of puberty, highlighting the need for healthcare professionals to closely monitor this age group during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse drug reactions of oral dexamethasone in children and adolescents with childhood acute lymphoblastic leukemia: a systematic review. Hu, L., Kim Emily, AN., Juh Allen, YE.[2022]

In a large observational study of 2150 patients with relapsed/refractory multiple myeloma, lenalidomide plus dexamethasone demonstrated a favorable safety profile, with lower incidence rates of neuropathy and infections compared to other treatments like bortezomib and thalidomide.

The study confirmed that lenalidomide's safety profile in a real-world setting is consistent with previous clinical trial data, with no new safety concerns identified, although it did show a higher incidence of neutropenia compared to bortezomib and thalidomide.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Noninterventional, Observational, European Post-Authorization Safety Study of Patients With Relapsed/Refractory Multiple Myeloma Treated With Lenalidomide. Gamberi, B., Berthou, C., Hernandez, M., et al.[2021]

Dexamethasone (Dx) can reduce the effectiveness of cisplatin (cDDP) in inducing apoptosis in osteosarcoma cells, decreasing apoptosis by 10-25% when used as a pre or cotreatment.

The protective effect of Dx is linked to the upregulation of the survival factor Akt and a potential direct action on the mitochondrial apoptotic pathway, suggesting that the timing of glucocorticoid administration in cancer treatment should be carefully considered.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dexamethasone protects against Cisplatin-induced activation of the mitochondrial apoptotic pathway in human osteosarcoma cells. Meyer, S., Eden, T., Kalirai, H.[2020]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Dexamethasone prescribing for cancer pain between palliative care and radiation oncology. [2022]

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

The use of corticosteroids in Swedish palliative care. [2009]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Impact of prophylactic dexamethasone on the efficacy of immune checkpoint inhibitors plus platinum-based chemotherapy in patients with advanced Non-Squamous Non-Small-Cell lung cancer. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Dexamethasone potentiates the antiangiogenic activity of docetaxel in castration-resistant prostate cancer. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Benefit of dexamethasone compared with prednisolone for childhood acute lymphoblastic leukaemia: results of the UK Medical Research Council ALL97 randomized trial. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Dexamethasone versus prednisone for induction therapy in childhood acute lymphoblastic leukemia: a systematic review and meta-analysis. [2018]

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

Study protocol: DexaDays-2, hydrocortisone for treatment of dexamethasone-induced neurobehavioral side effects in pediatric leukemia patients: a double-blind placebo controlled randomized intervention study with cross-over design. [2021]

8. Australia pubmed.ncbi.nlm.nih.gov

Adverse drug reactions of oral dexamethasone in children and adolescents with childhood acute lymphoblastic leukemia: a systematic review. [2022]

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

A Noninterventional, Observational, European Post-Authorization Safety Study of Patients With Relapsed/Refractory Multiple Myeloma Treated With Lenalidomide. [2021]

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

Dexamethasone protects against Cisplatin-induced activation of the mitochondrial apoptotic pathway in human osteosarcoma cells. [2020]

11. New Zealand pubmed.ncbi.nlm.nih.gov

Dexamethasone inhibits the proliferation of tumor cells. [2022]