Sulfasalazine in Decreasing Opioids Requirements in Breast Cancer Patients

NCT03847311 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 16055768565R21CA245411-02
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 2

Brief Summary

Cancer in general, and breast cancer in specific, is a significant health problem in the USA and the rest of the world. With the improvement of new surgical approaches and chemotherapies to manage breast cancer, the number of patients with breast cancer are now living longer. This great achievement created an unexpected problem. For some breast cancer patients, with bone metastases, the pain is worse than the cancer. The golden standard to manage pain is opioids. Patients with cancer-induced bone pain are now taking increasing doses of opioids to control their pain. Sadly, opioids come with significant side effects that limit the amount of opioids that can be safely given. Many attempts have been tried to create better regiments for pain control to lower the need for opioids. There has not been significant success in that area. A better approach would be to add a non-opioid agent that has dual mechanisms of action. This may create synergism to better control pain while lowering the doses of opioids needed and lowering side effects. Sulfasalazine poses such quality it is a safe anti-inflammatory drug with established safety profile. It has been in use for over 50 years for the treatment of inflammatory conditions such as arthritis. In addition to its anti-inflammatory characteristics, sulfasalazine has the capacity to decrease the survival of cancer cells, also to lower the number of inflammatory mediators released by cancer cells. In short, sulfasalazine inhibit the influx of cysteine into cancer cells and the efflux of glutamate. Cysteine is needed for cell survival against oxidative stress, while glutamate activate pain receptors. Therefore, sulfasalazine will act as anti-inflammatory, an agent to accelerate cancer cells death and decreasing the released glutamate which activate pain receptors. This one agent with 3 mechanisms of actions may lower the amount of opioid needed for these patients while maintaining or improving their pain. Lowering of opioid dosing may also improve the side effects associated with opioid use. The purpose of this trial is to co-administer sulfasalazine with opioids to cancer patients and characterize their pain and the opioid use. Our hypothesis is that adding sulfasalazine to the pain medication, will lower the amount of opioids used and lower the side effects. This may improve the quality of life for patients and decrease the risks of using high amount of opioids for the patients, their families, and society in general.

Conditions

Breast Cancer; Chronic Pain Due to Malignancy (Finding)

Outcome Measures

Primary Outcomes (1)

• Overall Pain Relief.

  Brief Pain Inventory (BPI) pain severity score. Scale range: 0 (no pain) to 10 (worst pain imaginable) Higher values represent a worse outcome.

  Twelve weeks

Secondary Outcomes (1)

• Decrease Opiate Dose.

  Twelve weeks

Study Arms (2)

Placebos

PLACEBO COMPARATOR

Subjects will receive sugar pill.

Drug: Placebos

Sulfasalazine

ACTIVE COMPARATOR

Subjects will receive the active drug.

Drug: Sulfasalazine

Interventions

Sulfasalazine DRUG

This group will receive supplies for 3 months of sulfasalazine at an initial dose of 0.5 gram three times a day for a week then at a dose of 1 gram three times a day for the remainder of the 3 months. Subjects will be asked to take their medications with every meal in addition to their regular pain medications.

Also known as: Active treatment

Sulfasalazine

Placebos DRUG

This group will receive supplies for 3 months of sugar pills three times a day for 3 months. Subjects will be asked to take their medications with every meal in addition to their regular pain medications.

Also known as: Non-active

Placebos

Eligibility Criteria

• Age: 18 Years - 94 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patient age 18 - \<95 years old capable of understanding and providing consent in English and capable of complying with the outcome used.
• Diagnosis of cancer with pain moderate to severe pain on stable doses of opioids
• day average numeric pain rating score (NPRS) for pain of at least 5/10 at baseline evaluation.
• Patient consents to double blind design of the experiment in a shared decision- making process with the treating physician.
• Pain duration of at least 6 weeks or more.
• Prognosis greater than 6 months.
• Able to take oral medication

You may not qualify if:

• Those receiving remuneration for their pain treatment (e.g., disability, worker's compensation).
• Those involved in active litigation relevant to their pain.
• Subjects with intestinal or urinary obstruction or at risk of such disorders.
• Porphyria
• Blood dyscrasias, hepatic or renal disease.
• Taking medications that may interact with sulfasalazine.
• Taking Lapatinib or Digoxin.
• No sustained hypercalcemia.
• Hypersensitivity to sulfasalazine, its metabolites, sulfonamides, or salicylates.
• The Subject is incarcerated.
• Those unable to read English and complete the assignment in English.
• Addictive behavior, severe clinical depression, or psychotic features.
• Possible pregnancy or lactation.

Sponsors & Collaborators

• University of Arizona: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Banner University Medical Center South

Tucson, Arizona, 85713, United States

Location

Banner University Medical Center North Campus

Tucson, Arizona, 85719, United States

Location

Related Publications (19)

• Lifetime Probability of Developing and Dying From Cancer for 23 sites, 2009-2011. 2014.

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  PMID: 35315341 DERIVED

MeSH Terms

Conditions

Breast Neoplasms; Signs and Symptoms

Interventions

Sulfasalazine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds

Results Point of Contact

• Title: Dr. Mohab Ibrahim
• Organization: University of Arizona

mohab@arizona.edu

(520) 626-7221

Study Officials

• Mohab M Ibrahim, PhD., MD

  University of Arizona

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The research pharmacist will randomize and prepare the drugs so that the drugs look similar, the pharmacist will dispense the drugs into vials, and label the drug so is not identified.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Comprehensive Pain Management Clinic Associate Professor, Anesthesiology

Model Details: Double blind study

Study Record Dates

• First Submitted: February 18, 2019
• First Posted: February 20, 2019
• Study Start: May 3, 2021
• Primary Completion: October 9, 2023
• Study Completion: October 9, 2023
• Last Updated: January 9, 2025
• Results First Posted: January 9, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)