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

February 13, 2024 updated by: THERAPIM PTY LTD

Phase 1b/2a Study Investigating ATX-101 in Combination With Platinum-based Chemotherapy in Platinum-sensitive, Recurrent Ovarian, Fallopian Tube and Primary Peritoneal Cancer

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

16

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Australia
    • New South Wales
      • Blacktown, New South Wales, Australia, 2148
        • Blacktown Hospital
    • Queensland
      • South Brisbane, Queensland, Australia, 4101
        • Mater Misericordiae Limited
    • Victoria
      • Frankston, Victoria, Australia, 3199
        • Peninsula and Southeast Oncology
      • Malvern, Victoria, Australia, 3144
        • Cabrini Hospital
    • Western Australia
      • Nedlands, Western Australia, Australia, 6009
        • Sir Charles Gairdner Hospital
      • Subiaco, Western Australia, Australia, 6008
        • St John of God Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Part 1 - ACD (Safety)
ATX-101 plus carboplatin and pegylated liposomal doxorubicin (ACD)
Drug: 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.
Experimental: Part 2 - ACD (Efficacy)
ATX-101 plus carboplatin and pegylated liposomal doxorubicin (ACD)
Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Time Frame: 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).
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.
Time Frame: Assessed from Day 1 to Week 85
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Part 1: To assess the Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of ATX-101 in combination with carboplatin/pegylated liposomal doxorubicin.
Time Frame: Assessed from Day 1 to Week 85
This is a composite outcome measure. Measured by Incidence, severity, and duration of treatment-emergent adverse events (TEAEs) and treatment-related TEAEs according to CTCAE v5.
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.
Time Frame: From pre-dose [within 30 min prior to infusion] until 60 min post infusion
Measured by characterizing the PK profile by estimating the Area under the drug concentration-time curve from time 0 to infinity (AUC0-inf).
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.
Time Frame: Assessed from Day 1 to Week 85
This is a composite outcome measure. Measured by Incidence, severity, and duration of treatment-emergent adverse events (TEAEs) and treatment-related TEAEs according to CTCAE v5.
Assessed from Day 1 to Week 85

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

THERAPIM PTY LTD

Collaborators

Novotech (Australia) Pty Limited

Investigators

  • Principal Investigator: Tarek Meniawy, A/Prof, Medical Oncologist, Sir Charles Gairdner Hospital Ground Floor, B Block, Hospital Avenue, Nedlands, WA 6009, Australia

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 1, 2021

Primary Completion (Actual)

November 30, 2023

Study Completion (Actual)

November 30, 2023

Study Registration Dates

First Submitted

March 4, 2021

First Submitted That Met QC Criteria

March 23, 2021

First Posted (Actual)

March 24, 2021

Study Record Updates

Last Update Posted (Actual)

February 14, 2024

Last Update Submitted That Met QC Criteria

February 13, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AM ATX101-03

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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