Tamoxifen and SUBA-Itraconzole Combination Testing in Ovarian Cancer

Ovarian Cancer Clinical Trial

— TICTOC  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05156892
• Other study ID #: TICTOC
• Status: Recruiting
• Phase: Phase 1
• Start date: September 4, 2022
• Est. completion date: January 1, 2025

Study information

• Verified date: December 2022
• Source: St Vincent's Hospital, Sydney
• Contact: Anthony Joshua, FRACP, MBBS, PhD
• Phone: +61 293555655
• Email: Anthony.Joshua[@]svha.org.au
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 44
• Est. completion date: January 1, 2025
• Est. primary completion date: January 1, 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Ovarian Epithelial
• Ovarian Cancer
• Ovarian Neoplasms

Intervention

Drug:
• SUBA-itraconazole
150 mg BD
• 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

Locations

Country	Name	City	State
Australia	Kinghorn Cancer Centre, St. Vincent's Hospital	Sydney	New South Wales

Sponsors (5)

Lead Sponsor	Collaborator
Anthony Joshua, FRACP	Concord Hospital, Prince of Wales Hospital, Sydney, Royal Prince Alfred Hospital, Sydney, Australia, St Vincent's Hospital, Sydney

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Recommended phase 2 dose of Tamoxifen in combination with Suba-itraconazole		1 years
Secondary	To determine overall response rate as determined by RECIST V1.1 and GCIG CA125 response criteria	ORR	2 years
Secondary	To determine the duration of response	DOR	2 years
Secondary	Incidence of Treatment-Emergent Adverse Events via CTCAE v5.0	Safety	2 years
Secondary	Serum concentration of tamoxifen and derivatives	Cmax	2 years
Secondary	Serum concentration of tamoxifen and derivatives	AUC	2 years
Secondary	Tissue concentration of tamoxifen and derivatives	mg/g	2 years
Secondary	Serum concentration of itraconazole	Cmax	2 years
Secondary	Serum concentration of itraconazole	AUC	2 years
Secondary	Tissue concentration of itraconazole	mg/g	2 years