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

NCT04814875 | Terminated Phase 1

• 1 other identifier: AM ATX101-03
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 6

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

Outcome Measures

Primary Outcomes (2)

• Part 1: To determine the maximum tolerated dose (MTD) of ATX-101 in combination with carboplatin/pegylated liposomal doxorubicin. Measured by incidence of Dose Limiting Toxicity.

  Measured by incidence of Dose Limiting Toxicity (DLT): the MTD is defined as the highest dose level at which ≤ 1/6 of treated participants experience a DLT during a DLT period of 30 days. The RP2D will be either the MTD or the highest tested dose level if MTD is not reached.

  Assessed from the time of the first administered dose of ATX-101 up to the last treatment in Cycle 2 (i.e. Days 2 to 30).

• Part 2: To assess the progression free survival (PFS) of ATX-101 in combination with carboplatin/pegylated liposomal doxorubicin. Measured by Tumor assessments.

  Measured by tumor imaging (CT-scan or MRI) in accordance to Response Evaluation Criteria in Solid Tumors (RECIST) every 3 months over a treatment/observation period of 21 months for the individual patient. Tumor images will be compared and changes will be noted over the entire time. PFS means that the sum of diameters of target lesions will not increase by more than 20%, taking as reference the smallest sum measured.

  Assessed from Day 1 to Week 85

Secondary Outcomes (3)

• Part 1: To assess the Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of ATX-101 in combination with carboplatin/pegylated liposomal doxorubicin.

  Assessed from Day 1 to Week 85

• Part 1: To characterize the plasma PK profile of ATX-101 following IV infusion in combination with carboplatin/pegylated liposomal doxorubicin.

  From pre-dose [within 30 min prior to infusion] until 60 min post infusion

• Part 2: To assess the Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of ATX-101 in combination with carboplatin/pegylated liposomal doxorubicin.

  Assessed from Day 1 to Week 85

Study Arms (2)

Part 1 - ACD (Safety)

EXPERIMENTAL

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

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

Part 2 - ACD (Efficacy)

EXPERIMENTAL

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

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

Interventions

ATX-101 + Carboplatin + Pegylated liposomal doxorubicin (ACD) 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 1 - ACD (Safety); Part 2 - ACD (Efficacy)

Eligibility Criteria

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

You may qualify if:

• Women ≥ 18 years of age
• Is not a woman of childbearing potential:
• 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;
• 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.
• Signed written informed consent
• Histologically confirmed high grade serous or endometrioid carcinoma of the ovary, fallopian tube, or primary peritoneal cancer
• to 3 prior systemic treatment lines. Prior maintenance therapy with bevacizumab or PARP inhibitors is permitted.
• Platinum-sensitive carcinoma, defined as disease progression after ≥ 6 months following the most recent platinum-based therapy of the disease
• Measurable disease on CT/MRI scan according to RECIST 1.1
• ECOG Performance status 0 to 1
• Life expectancy of at least 6 months
• Meet the following laboratory requirements:
• Hemoglobin (HGB) ≥ 100 × 109/L
• Absolute neutrophil count (ANC) ≥ 1.5 × 109/L
• Platelet count ≥ 100 × 109/L

You may not qualify if:

• Have received an anti-cancer/investigational drug within 4 weeks prior to study drug administration
• 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
• Have not recovered from AEs (≥ CTCAE Grade 2 other than alopecia) due to agent(s) administered more than 4 weeks earlier
• Radiotherapy within 4 weeks prior to study drug administration
• Major surgery or significant trauma within 28 days (4 weeks) of Screening
• Anticipated requirement for surgery or initiation of anti-cancer therapy, other than described in this study protocol, during the study period
• Known hypersensitivity to any of the combination partners of ATX-101
• 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
• Cardiac failure NYHA III/IV.
• LVEF \< 50% (ECHO or MUGA must not be older than 12 weeks)
• QTcF \> 470 msec
• 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
• Pregnant or breast-feeding women
• Unwilling or unable to follow protocol requirements
• A past positive status of HIV and/or positive for HIV at Screening

Sponsors & Collaborators

• THERAPIM PTY LTD: lead
• Novotech (Australia) Pty Limited: collaborator

Study Sites (6)

Blacktown Hospital

Blacktown, New South Wales, 2148, Australia

Location

Mater Misericordiae Limited

South Brisbane, Queensland, 4101, Australia

Location

Peninsula and Southeast Oncology

Frankston, Victoria, 3199, Australia

Location

Cabrini Hospital

Malvern, Victoria, 3144, Australia

Location

Sir Charles Gairdner Hospital

Nedlands, Western Australia, 6009, Australia

Location

St John of God Hospital

Subiaco, Western Australia, 6008, Australia

Location

MeSH Terms

Conditions

Ovarian Neoplasms; Fallopian Tube Neoplasms

Interventions

Carboplatin; liposomal doxorubicin

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Fallopian Tube Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals

Study Officials

• Tarek Meniawy, A/Prof

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 4, 2021
• First Posted: March 24, 2021
• Study Start: September 1, 2021
• Primary Completion: November 30, 2023
• Study Completion: November 30, 2023
• Last Updated: February 14, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

AU (6)