A Study to Evaluate the Combination of ATX-101 and Platinum-based Chemotherapy

NCT ID: NCT04814875

Last Updated: 2024-02-14

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-09-01
• Study Completion Date: 2023-11-30

Brief Summary

This is a Phase 1b/2a multicenter study, which consists of two parts:

Part 1: the Phase 1b part of the study will investigate the safety of the combination of ATX-101 with carboplatin/pegylated liposomal doxorubicin (ACD). ATX-101 will be administered intravenously in three escalation cohorts: 20, 30, and 45 mg/m² according to a 3+3 design. In the case where 20 mg/m² is not tolerated, the dose can be de-escalated to 15 mg/m².

Part 2: the Phase 2a part of the study will investigate the efficacy and safety of ACD.

ATX-101 will be administered at the dose defined in Part 1 of the study.

Treatment will continue up to six cycles or until disease progression or unacceptable toxicity, participant withdrawal of consent, non-compliance, lost to follow-up, or withdrawal at the Investigators discretion, whichever occurs first.

Conditions

Ovarian Cancer; Fallopian Tube Cancer; Primary Peritoneal Carcinoma; High Grade Serious or Endometrioid Carcinoma of the Ovary, Fallopian Tube, or Primary Peritoneal Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part 1 - ACD (Safety)

ATX-101 plus carboplatin and pegylated liposomal doxorubicin (ACD)

Group Type: EXPERIMENTAL

ATX-101 + Carboplatin + Pegylated liposomal doxorubicin (ACD)

Intervention Type: DRUG

Pegylated liposomal doxorubicin (30 mg/m²) will be administered intravenously on Day 1 of each 28-day cycle; carboplatin (AUC5) will be administered intravenously on Day 1 of each cycle.

ATX-101 will be administered intravenously on Day 2 of each cycle in three escalation cohorts: 20, 30, and 45 mg/m² according to a 3+3 design.

Part 2 - ACD (Efficacy)

ATX-101 plus carboplatin and pegylated liposomal doxorubicin (ACD)

Group Type: EXPERIMENTAL

ATX-101 + Carboplatin + Pegylated liposomal doxorubicin (ACD)

Intervention Type: DRUG

Pegylated liposomal doxorubicin (30 mg/m²) will be administered intravenously on Day 1 of each 28-day cycle; carboplatin (AUC5) will be administered intravenously on Day 1 of each cycle.

ATX-101 will be administered intravenously on Day 2 of each cycle in three escalation cohorts: 20, 30, and 45 mg/m² according to a 3+3 design.

Interventions

ATX-101 + Carboplatin + Pegylated liposomal doxorubicin (ACD)

Pegylated liposomal doxorubicin (30 mg/m²) will be administered intravenously on Day 1 of each 28-day cycle; carboplatin (AUC5) will be administered intravenously on Day 1 of each cycle.

ATX-101 will be administered intravenously on Day 2 of each cycle in three escalation cohorts: 20, 30, and 45 mg/m² according to a 3+3 design.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Women ≥ 18 years of age

2. Is not a woman of childbearing potential:

1. Surgically sterile (i.e., had a bilateral tubal ligation, hysterectomy, salpingectomy, or bilateral oophorectomy at least 6 months prior to Day 1 of the study) or;

2. Postmenopausal for at least 1 year prior to Day 1 of the study, and have follicle stimulating hormone levels in the postmenopausal range for the study site.

3. Signed written informed consent

4. Histologically confirmed high grade serous or endometrioid carcinoma of the ovary, fallopian tube, or primary peritoneal cancer

5. 1 to 3 prior systemic treatment lines. Prior maintenance therapy with bevacizumab or PARP inhibitors is permitted.

6. Platinum-sensitive carcinoma, defined as disease progression after ≥ 6 months following the most recent platinum-based therapy of the disease

7. Measurable disease on CT/MRI scan according to RECIST 1.1

8. ECOG Performance status 0 to 1

9. Life expectancy of at least 6 months

10. Meet the following laboratory requirements:

1. Hemoglobin (HGB) ≥ 100 × 109/L

2. Absolute neutrophil count (ANC) ≥ 1.5 × 109/L

3. Platelet count ≥ 100 × 109/L

4. aPTT/PT ≤ 1.5 x ULN

5. Total bilirubin level ≤ 1.5 × ULN

6. AST and ALT ≤ 2.5 × ULN (≤ 5 × ULN if liver metastasis present)

7. Creatinine Clearance > 60 mL/min, as calculated by Cockcroft-Gault formula, or serum creatinine ≤ 1.5 × ULN.

Exclusion Criteria

1. Have received an anti-cancer/investigational drug within 4 weeks prior to study drug administration

2. Have received a vaccine for COVID-19 within 14 days prior to the first dose of ATX-101 or are scheduled/intend to have a COVID-19 vaccine on Day 1 or during the DLT period (i.e. C1D2 [Day 2] through to C2D2 [Day 30]) of the study

3. Have not recovered from AEs (≥ CTCAE Grade 2 other than alopecia) due to agent(s) administered more than 4 weeks earlier

4. Radiotherapy within 4 weeks prior to study drug administration

5. Major surgery or significant trauma within 28 days (4 weeks) of Screening

6. Anticipated requirement for surgery or initiation of anti-cancer therapy, other than described in this study protocol, during the study period

7. Known hypersensitivity to any of the combination partners of ATX-101

8. Any malignancy over the last 5 years, other than ovarian/fallopian tube/primary peritoneal cancer, with exception of basal cell carcinoma or squamous cell carcinoma of the skin or carcinoma in situ of the cervix that is considered cured by excision

9. Cardiac failure NYHA III/IV.

10. LVEF < 50% (ECHO or MUGA must not be older than 12 weeks)

11. QTcF > 470 msec

12. Any organ dysfunction or current acute or chronic disease, other than the study indication, that would significantly increase the expected risk in participants participating in the study, in the judgment of the Investigator

13. Pregnant or breast-feeding women

14. Unwilling or unable to follow protocol requirements

15. A past positive status of HIV and/or positive for HIV at Screening

16. Active Hepatitis B or C. In participants with a history of Hepatitis B or Hepatitis C infection, HBsAg and HCV RNA tests have to be negative.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Novotech (Australia) Pty Limited

INDUSTRY

Sponsor Role: collaborator

THERAPIM PTY LTD

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Tarek Meniawy, A/Prof

Role: PRINCIPAL_INVESTIGATOR

Medical Oncologist, Sir Charles Gairdner Hospital Ground Floor, B Block, Hospital Avenue, Nedlands, WA 6009, Australia

Locations

Blacktown Hospital

Blacktown, New South Wales, Australia

Mater Misericordiae Limited

South Brisbane, Queensland, Australia

Peninsula and Southeast Oncology

Frankston, Victoria, Australia

Cabrini Hospital

Malvern, Victoria, Australia

Sir Charles Gairdner Hospital

Nedlands, Western Australia, Australia

St John of God Hospital

Subiaco, Western Australia, Australia

Countries

Australia

Other Identifiers

AM ATX101-03

Identifier Type: -

Identifier Source: org_study_id