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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04814875
Recruitment Status : Recruiting
First Posted : March 24, 2021
Last Update Posted : July 19, 2022
Sponsor:
Collaborator:
Novotech (Australia) Pty Limited
Information provided by (Responsible Party):
THERAPIM PTY LTD

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.


Condition or disease Intervention/treatment Phase
Ovarian Cancer Fallopian Tube Cancer Primary Peritoneal Carcinoma High Grade Serious or Endometrioid Carcinoma of the Ovary, Fallopian Tube, or Primary Peritoneal Cancer Drug: ATX-101 + Carboplatin + Pegylated liposomal doxorubicin (ACD) Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 78 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1b/2a Study Investigating ATX-101 in Combination With Platinum-based Chemotherapy in Platinum-sensitive, Recurrent Ovarian, Fallopian Tube and Primary Peritoneal Cancer
Actual Study Start Date : September 1, 2021
Estimated Primary Completion Date : March 31, 2025
Estimated Study Completion Date : March 31, 2025


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.





Primary Outcome Measures :
  1. 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.

  2. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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).

  3. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04814875


Contacts
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Contact: Jens-Peter Marschner, Dr +61 756 999 630 jpmarschner@apimtherapeutics.com

Locations
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Australia, New South Wales
Blacktown Hospital Recruiting
Blacktown, New South Wales, Australia, 2148
Contact: Bo Gao         
Principal Investigator: Bo Gao         
Australia, Victoria
Peninsula and Southeast Oncology Recruiting
Frankston, Victoria, Australia, 3199
Contact: Vinod Ganju         
Principal Investigator: Vinod Ganju         
Cabrini Hospital Recruiting
Malvern, Victoria, Australia, 3144
Contact: Gary Richardson         
Principal Investigator: Gary Richardson         
Australia, Western Australia
Sir Charles Gairdner Hospital Recruiting
Nedlands, Western Australia, Australia, 6009
Contact: Tarek Meniawy         
Principal Investigator: Tarek Meniawy         
St John of God Hospital Recruiting
Subiaco, Western Australia, Australia, 6008
Contact: Tarek Meniawy         
Principal Investigator: Tarek Meniawy         
Sponsors and Collaborators
THERAPIM PTY LTD
Novotech (Australia) Pty Limited
Investigators
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Principal Investigator: Tarek Meniawy, A/Prof Medical Oncologist, Sir Charles Gairdner Hospital Ground Floor, B Block, Hospital Avenue, Nedlands, WA 6009, Australia
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Responsible Party: THERAPIM PTY LTD
ClinicalTrials.gov Identifier: NCT04814875    
Other Study ID Numbers: AM ATX101-03
First Posted: March 24, 2021    Key Record Dates
Last Update Posted: July 19, 2022
Last Verified: July 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma
Fallopian Tube Neoplasms
Carcinoma, Ovarian Epithelial
Carcinoma, Endometrioid
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Ovarian Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Ovarian Diseases
Adnexal Diseases
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Fallopian Tube Diseases
Adenocarcinoma
Endometrial Neoplasms
Uterine Neoplasms
Carboplatin
Doxorubicin
Liposomal doxorubicin
Antineoplastic Agents
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action