Tamoxifen and SUBA-Itraconzole Combination Testing in Ovarian Cancer (TICTOC)

A Phase I/II Trial Investigating the Tolerability, Toxicity and Efficacy of Tamoxifen and SUBA-Itraconazole in Patients With Platinum Resistant Recurrent Epithelial Ovarian Cancer

The study's purpose is to understand the effects of a new treatment (suba-itraconazole and tamoxifen) in epithelial ovarian cancer.

Who is it for? Patients may be eligible to join this study with ovarian cancer resistant to platinum-based chemotherapy agents

Study Details:

Participants will receive different doses of tamoxifen and suba-itraconazole to determine the optimal combination dose.

Participants will be seen by the investigators once a week for the first 3 weeks and then once every 4 weeks. Participant will be reviewed by a clinician and undergo regular blood tests, cardiac monitoring and imaging assessments.

Study Overview

• Status: Active, not recruiting
• Conditions: Ovarian Cancer
• Intervention / Treatment: Drug: SUBA-itraconazole; Drug: Tamoxifen

Detailed Description

A phase 1/2 study of Suba-itraconazole and Tamoxifen in platinum resistant ovarian carcinoma

• Study Type: Interventional
• Enrollment (Estimated): 44
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 2010
      • Kinghorn Cancer Centre, St. Vincent's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Histological or cytological-based diagnosis of high grade and low grade epithelial ovarian cancer. Patients with clear cell ovarian cancers are not eligible to participate in this study due to higher risk of thromboemboli which could be increased by Tamoxifen.
2. Platinum resistant ovarian cancer with no more than 4 lines of previous systemic therapy (re-treatment with a previous regimen is only counted as 1 line of therapy).
3. Age > 18 years.
4. Patient must be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures
5. Eastern Cooperative Oncology Group Performance Status of 0 or 1

6. Adequate hematologic and organ function within 14 days before the first study treatment on Day 1 of Cycle 1, defined by the following:

   • Neutrophils (absolute neutrophil count ANC >1.5X10^9/L,)
   • Hemoglobin >9 g/dL
   • Platelet count >100,000/L
   • Serum albumin >3 g/dL

   • Total bilirubin 1.5 ≤the upper limit of normal (ULN) and AST and ALT ≤2.5 XULN, with the following exception:

     • Patients with known Gilbert syndrome who have serum bilirubin ≤3XULN may be enrolled.
     • Patients with documented liver metastasis may have AST and ALT ≤5XULN
   • PTT (or aPTT) and INR ≤1.5XULN (except for patients receiving anticoagulation therapy)
   • Serum creatinine ≤ 1.5XULN or creatinine clearance >50 mL/min based on Cockcroft-Gault glomerular filtration rate estimation: (140 - age) X(weight in kg) X0.85 (if female) 72 X(serum creatinine in mg/dL)
7. Life expectancy of at least 3 months
8. Have at least 1 measurable lesion assessable using standard techniques by RECIST v1.1. Patients without any measurable disease may be enrolled on a case-by-case basis in discussion with study principle investigator
9. At least 4 weeks washout period from previous line of treatment (including hormonal treatment) , 2 weeks from radiotherapy
10. Ability to swallow and retain oral medications (without crushing, dissolving or chewing tablets)
11. Willing and able to comply with all study requirements, including treatment (e.g. able to swallow tablets), timing and/or nature of required assessments

Exclusion Criteria:

1. Patients with any other prior malignancy from which the patient has been disease free for less than 3 years, with the exception of adequately treated and cured basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of any site or any other cancer as approved by study principle investigator
2. Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic or asymptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
3. History of or current evidence of HIV infection, Viral hepatitis (e.g., positive for hepatitis B surface antigen [HBsAg] or hepatitis C virus [HCV] antibody at screening)
4. Patients with symptomatic central nervous system (CNS) metastasis and/or carcinomatous meningitis. Patients with treated CNS metastases are eligible for this study if not receiving corticosteroids and/or anticonvulsants for at least 7 days prior to first dose of study treatment, and the disease is asymptomatic and radiographically stable for at least 2 weeks after completion of CNS-directed therapy. Patients with untreated stable or asymptomatic brain metastases may be enrolled on a case-by-case basis in discussion with study principal investigator.
5. Patients with existing or past history of deep venous thromboembolism are excluded, unless stable on anticoagulation.
6. Patients with Khorana score of greater than or equal to 3 (see https://www.mdcalc.com/khorana-risk-score-venousthromboembolism- cancer-patients)
7. Known hypersensitivity or contraindication to any component of the study treatment.
8. Inability to comply with study and follow-up procedures.
9. Patients who have not recovered (≤ grade 2) from adverse events related to previous treatments, unless approved by study principle investigator
10. Patients unable to swallow orally administered medications and patients with gastrointestinal impairment that could affect the ability to take or absorption of oral medications including sub-acute or complete bowel obstruction.
11. Participants with uncontrolled intercurrent illness
12. Participants not recovered from all toxicities related to prior anticancer therapies to CTCAE grade<1 apart from alopecia
13. Patients with psychiatric illness/social situations that would limit compliance with study requirements

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose-escalation/ expansion; SUBA-itraconazole (oral 150mg twice daily) and escalating dose of Tamoxifen (oral once daily) then expansion cohort	Drug: SUBA-itraconazole; 150 mg BD; Drug: Tamoxifen; Dose Escalation: Cohort 1: 20 mg OD Cohort 2: 40 mg OD Cohort 3: 60 mg OD Dose-Expansion: Recommended dose from dose-escalation phase of study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Recommended phase 2 dose of Tamoxifen in combination with Suba-itraconazole	1 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To determine overall response rate as determined by RECIST V1.1 and GCIG CA125 response criteria	ORR	2 years
To determine the duration of response	DOR	2 years
Incidence of Treatment-Emergent Adverse Events via CTCAE v5.0	Safety	2 years
Serum concentration of tamoxifen and derivatives	Cmax	2 years
Serum concentration of tamoxifen and derivatives	AUC	2 years
Tissue concentration of tamoxifen and derivatives	mg/g	2 years
Serum concentration of itraconazole	Cmax	2 years
Serum concentration of itraconazole	AUC	2 years
Tissue concentration of itraconazole	mg/g	2 years

Collaborators and Investigators

• Sponsor: Anthony Joshua, FRACP
• Collaborators: St Vincent's Hospital, Sydney; Royal Prince Alfred Hospital, Sydney, Australia; Prince of Wales Hospital, Sydney; Concord Hospital
• Investigators: Principal Investigator: Anthony Joshua, FRACP, MBBS, PhD, St Vincent's Hospital, Sydney

Study record dates

Study Major Dates

• Study Start (Actual): September 4, 2022
• Primary Completion (Estimated): January 1, 2026
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: October 19, 2021
• First Submitted That Met QC Criteria: December 13, 2021
• First Posted (Actual): December 14, 2021

Study Record Updates

• Last Update Posted (Actual): May 15, 2025
• Last Update Submitted That Met QC Criteria: May 12, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Tamoxifen; Ovarian Cancer; Platinum resistant; SUBA-Itraconazole
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Neoplasms by Histologic Type; Genital Diseases, Female; Endocrine Gland Neoplasms; Neoplasms, Glandular and Epithelial; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Gonadal Disorders; Carcinoma; Carcinoma, Ovarian Epithelial; Ovarian Neoplasms; Anti-Infective Agents; Antineoplastic Agents; Antifungal Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Enzyme Inhibitors; Bone Density Conservation Agents; Steroid Synthesis Inhibitors; Hormone Antagonists; Cytochrome P-450 Enzyme Inhibitors; Estrogen Antagonists; Cytochrome P-450 CYP3A Inhibitors; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; 14-alpha Demethylase Inhibitors; Tamoxifen; Itraconazole
• Other Study ID Numbers: TICTOC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No Plan to share participant data with individuals outside this trial

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No