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

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

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.

Study Phase

Phase 1/Phase 2

Study Type

Interventional

Primary Outcome

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.

Secondary Outcome

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

Condition

Ovarian Cancer

Intervention

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

Study Arms / Comparison Groups

 Part 1 - ACD (Safety)

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

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status

Drug

Estimated Enrollment

Start Date

September 1, 2021

Completion Date

March 31, 2025

Primary Completion Date

March 31, 2025

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.

Gender

Female

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Tarek Meniawy, A/Prof, +61 756 999 630, [email protected]

Location Countries

Australia

Location Countries

Australia

Administrative Informations

NCT ID

NCT04814875

Organization ID

AM ATX101-03

Responsible Party

Sponsor

Study Sponsor

THERAPIM PTY LTD

Collaborators

 Novotech (Australia) Pty Limited

Study Sponsor

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

Verification Date

November 2022