A Study to Evaluate the Combination of ATX-101 and Platinum-based Chemotherapy
Primary Purpose
Ovarian Cancer, Fallopian Tube Cancer, Primary Peritoneal Carcinoma
Status
Recruiting
Phase
Phase 1
Locations
Australia
Study Type
Interventional
Intervention
ATX-101 + Carboplatin + Pegylated liposomal doxorubicin (ACD)
Sponsored by
About this trial
This is an interventional treatment trial for Ovarian Cancer
Eligibility Criteria
Inclusion Criteria:
- 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
- 1 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
- aPTT/PT ≤ 1.5 x ULN
- Total bilirubin level ≤ 1.5 × ULN
- AST and ALT ≤ 2.5 × ULN (≤ 5 × ULN if liver metastasis present)
- Creatinine Clearance > 60 mL/min, as calculated by Cockcroft-Gault formula, or serum creatinine ≤ 1.5 × ULN.
Exclusion Criteria:
- 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
- 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.
Sites / Locations
- Blacktown HospitalRecruiting
- Mater Misericordiae Limited
- Peninsula and Southeast OncologyRecruiting
- Cabrini HospitalRecruiting
- Sir Charles Gairdner HospitalRecruiting
- St John of God HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Part 1 - ACD (Safety)
Part 2 - ACD (Efficacy)
Arm Description
ATX-101 plus carboplatin and pegylated liposomal doxorubicin (ACD)
ATX-101 plus carboplatin and pegylated liposomal doxorubicin (ACD)
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
Part 1: To assess the Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of ATX-101 in combination with carboplatin/pegylated liposomal doxorubicin.
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.
Part 1: To characterize the plasma PK profile of ATX-101 following IV infusion in combination with carboplatin/pegylated liposomal doxorubicin.
Measured by characterizing the PK profile by estimating the Area under the drug concentration-time curve from time 0 to infinity (AUC0-inf).
Part 2: To assess the Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of ATX-101 in combination with carboplatin/pegylated liposomal doxorubicin.
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.
Full Information
NCT ID
NCT04814875
First Posted
March 4, 2021
Last Updated
November 9, 2022
Sponsor
THERAPIM PTY LTD
Collaborators
Novotech (Australia) Pty Limited
1. Study Identification
Unique Protocol Identification Number
NCT04814875
Brief Title
A Study to Evaluate the Combination of ATX-101 and Platinum-based Chemotherapy
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
Study Type
Interventional
2. Study Status
Record Verification Date
November 2022
Overall Recruitment Status
Recruiting
Study Start Date
September 1, 2021 (Actual)
Primary Completion Date
March 31, 2025 (Anticipated)
Study Completion Date
March 31, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
THERAPIM PTY LTD
Collaborators
Novotech (Australia) Pty Limited
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ovarian Cancer, Fallopian Tube Cancer, Primary Peritoneal Carcinoma, High Grade Serious or Endometrioid Carcinoma of the Ovary, Fallopian Tube, or Primary Peritoneal Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
78 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Part 1 - ACD (Safety)
Arm Type
Experimental
Arm Description
ATX-101 plus carboplatin and pegylated liposomal doxorubicin (ACD)
Arm Title
Part 2 - ACD (Efficacy)
Arm Type
Experimental
Arm Description
ATX-101 plus carboplatin and pegylated liposomal doxorubicin (ACD)
Intervention Type
Drug
Intervention Name(s)
ATX-101 + Carboplatin + Pegylated liposomal doxorubicin (ACD)
Intervention Description
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 Measure Information:
Title
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.
Description
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.
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).
Title
Part 2: To assess the progression free survival (PFS) of ATX-101 in combination with carboplatin/pegylated liposomal doxorubicin. Measured by Tumor assessments.
Description
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.
Time Frame
Assessed from Day 1 to Week 85
Secondary Outcome Measure Information:
Title
Part 1: To assess the Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of ATX-101 in combination with carboplatin/pegylated liposomal doxorubicin.
Description
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.
Time Frame
Assessed from Day 1 to Week 85
Title
Part 1: To characterize the plasma PK profile of ATX-101 following IV infusion in combination with carboplatin/pegylated liposomal doxorubicin.
Description
Measured by characterizing the PK profile by estimating the Area under the drug concentration-time curve from time 0 to infinity (AUC0-inf).
Time Frame
From pre-dose [within 30 min prior to infusion] until 60 min post infusion
Title
Part 2: To assess the Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of ATX-101 in combination with carboplatin/pegylated liposomal doxorubicin.
Description
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.
Time Frame
Assessed from Day 1 to Week 85
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
1 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
aPTT/PT ≤ 1.5 x ULN
Total bilirubin level ≤ 1.5 × ULN
AST and ALT ≤ 2.5 × ULN (≤ 5 × ULN if liver metastasis present)
Creatinine Clearance > 60 mL/min, as calculated by Cockcroft-Gault formula, or serum creatinine ≤ 1.5 × ULN.
Exclusion Criteria:
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
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jens-Peter Marschner, Dr
Phone
+61 756 999 630
Email
jpmarschner@apimtherapeutics.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tarek Meniawy, A/Prof
Organizational Affiliation
Medical Oncologist, Sir Charles Gairdner Hospital Ground Floor, B Block, Hospital Avenue, Nedlands, WA 6009, Australia
Official's Role
Principal Investigator
Facility Information:
Facility Name
Blacktown Hospital
City
Blacktown
State/Province
New South Wales
ZIP/Postal Code
2148
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Bo Gao
First Name & Middle Initial & Last Name & Degree
Bo Gao
Facility Name
Mater Misericordiae Limited
City
South Brisbane
State/Province
Queensland
ZIP/Postal Code
4101
Country
Australia
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Catherine Shannon, Dr
First Name & Middle Initial & Last Name & Degree
Catherine Shannon, Dr
Facility Name
Peninsula and Southeast Oncology
City
Frankston
State/Province
Victoria
ZIP/Postal Code
3199
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Vinod Ganju
First Name & Middle Initial & Last Name & Degree
Vinod Ganju
Facility Name
Cabrini Hospital
City
Malvern
State/Province
Victoria
ZIP/Postal Code
3144
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gary Richardson
First Name & Middle Initial & Last Name & Degree
Gary Richardson
Facility Name
Sir Charles Gairdner Hospital
City
Nedlands
State/Province
Western Australia
ZIP/Postal Code
6009
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tarek Meniawy
First Name & Middle Initial & Last Name & Degree
Tarek Meniawy
Facility Name
St John of God Hospital
City
Subiaco
State/Province
Western Australia
ZIP/Postal Code
6008
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tarek Meniawy
First Name & Middle Initial & Last Name & Degree
Tarek Meniawy
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Study to Evaluate the Combination of ATX-101 and Platinum-based Chemotherapy
We'll reach out to this number within 24 hrs