A Phase I study of Oxyfedrine and Sulfasalazine in Patients with Solid Tumor

JRCT ID: jRCT2031230531

Registered date:22/12/2023

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: advanced or recurrent solid tumor unresectable and unresponsive to conventional therapy
• Date of first enrollment: 15/01/2024
• Target sample size: 54
• Study type: Interventional

Intervention(s)

(Dose-escalation part)
Tolerability of combination therapy with Oxyfedrine and Sulfasalazine in the dose-escalation part will be assessed, and the recommended dose (RD) in the dose-expansion part will be determined.
The doses of Oxyfedrine and Sulfasalazine will start at dose level 1a and move to dose level 2, dose level 3 or dose level -1 according to the criteria.
Level 1a : Sulfasalazine 6 g/day, Oxyfedrine 24 mg/day
Level 1b : Sulfasalazine 6 g/day, Oxyfedrine 48 mg/day
Level 2a : Sulfasalazine 8 g/day, Oxyfedrine 24 mg/day
Level 2b : Sulfasalazine 8 g/day, Oxyfedrine 48 mg/day
Oxyfedrine and Sulfasalazine will be administered orally 4 times a day.One cycle is defined as 4 weeks.

(Dose-expansion part)
The RD determined on the results of the dose-escalation part will be administered.

Outcome(s)

• Primary Outcome: Incidence of DLTs in the dose-escalation part

Secondary Outcome

-Incidence of adverse events
-Objective response rate
-Progression-free survival
-Duration of response
-Time to treatment failure
-Disease control rate
-Overall survival
-Phamacokinetics

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1.Patients who have voluntarily provided written consent for participation in the study.
2.Patients aged 18 years or older at the time of providing informed consent.
3.Patients diagnosed with solid tumor who:
(Dose-escalation part)
Histologically or cytologically confirmed unresectable or recurrent solid tumor
(Dose-expansion part)
Histologically or cytologically confirmed unresectable or recurrent solid tumor to be one of the following
-Cohort A: Stomach cancer
-Cohort B: Renal cell carcinoma
-Cohort C: Triple negative breast cancer
4.Refractory or intolerant to conventional therapy
5.Measurable disease according to RECIST version 1.1
6.Patients with PS (ECOG) of 0 to 1
7.Life expectancy of at least 12 weeks
8.Patients who have adequate organ function and whose latest laboratory results within 7 days prior to enrollment meet all the following criteria.
-ANC >= 1500 /mm3
-Platelet count >= 100,000/ mm3
-Hemoglobin >= 9.0 g/dL
-Calculated (with the Cockcroft-Gault formula) or measured creatinine clearance >= 40 mL/min
-Total bilirubin <= 1.5XULN
-AST, ALT<=100 IU/L
9.Males and females of childbearing potential agree to use contraception from the time consent is obtained until at least 30 days after the last dose of study drug.

Exclude criteria

1.Patients with a history of administration of sulfasalazine or 5-ASA preparations.
2.Patients receiving systemic beta-stimulants or beta-blockers (although temporary use of beta-stimulants for asthma attacks is acceptable).
3.Patients with symptomatic brain metastases or meningeal dissemination
4.Patients who are pregnant or breastfeeding
5.Patients with active overlapping cancers requiring treatment such as drug therapy or surgery.
However, patients with history of carcinoma situ which are considered to be cured by local treatment, lesions equivalent to intramucosal carcinoma or non-metastatic prostate cancer requiring systemic treatment are excluded.
6.Pateints who require the following anticancer therapy
-Any prior therapy (including chemotherapy, molecular targeted therapy, antibody therapy, hormone therapy or immune therapy) within 14 days before the start of the protocol treatment. However, bisphosphonate or denosumab for bone lesion, LH-RH agonist or GnRH antagonist for prostate cancer are allowed.
-Radiation therapy or Radiopharmaceutical therapy within 28 days before the start of the protocol treatment. However, palliative radiation therapy within 14 days before the start of theprotocol treatment is allowed.
7. Patients who have the following infectious diseases
- HBsAg-positive
-HBsAb-positive or HBcAb-positive
-HCVAb-positive
-HIV-positive
-Other active infectious diseases requiring treatment.
8. Patients with the following previous or current history
-Uncontrol ascites, pleural or pericardial effusion
-QT prolongation syndrome
-Interstitial pneumonia or pulmonary fibrosis
-Psychosis or propensity for medication overuse
-Hypersensitivity to sulfa drugs or salicylic acid preparations
-Hypersensitivity or serious adverse reactions to beta-stimulants
-Inflammatory bowel disease
9.Patients who are receiving systemic steroids or immunosuppressive drug therapy at enrollment.
Note : It is allowed in the following cases.
- A dose <= 10 mg / day of prednisolone
- Temporary use for testing or prophylactic administration for allergic reactions, or for reduction of edema associated with radiotherapy
10. Patients who does not have recovered from any adverse events (AEs) of previous anticancer therapy.
Note : Hematological abnormality meet inclusion criteria 6, CTCAE grade 2 peripheral neuropathy, alopecia, hyperpigmentation, and the cases judged by the investigator to have no safety problems are allowed.
11. Patients with myocardial infarction, congestive heart failure (New York Heart Association class III or IV), unstable angina or arrhythmia requiring treatment within 6 months prior to enrollment.
12. Patients who have a history of major surgery(minimal surgery is excluded, for example lymph node biopsy, core biopsy or implantation of port etc.) within 4 weeks prior to enrollment.
13. Patients who are unable to abstain from alcohol during the period of study drug administration.
14. Patients with other significant abnormalities.
15. Patients who are regarded as inappropriate for enrollment by investigators.

Related Information

• Primary Sponsor: Kohei Shitara
• Secondary Sponsor: Hiromichi Nakajima
• Source(s) of Monetary Support: Japan Agency for Medical Research and Development,FerroptoCure Inc.