To Evaluate the Safety and Efficacy of Ipatasertib (GDC-0068) in Combination With Paclitaxel in Platinum-resistant Recurrent Epithelial Ovarian Cancer

NCT ID: NCT04561817

Last Updated: 2020-10-06

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-10-01
• Study Completion Date: 2023-10-01

Brief Summary

This is a phase II open label, non-randomized, study to evaluate the safety and efficacy of Ipatasertib (GDC-0068) in combination with paclitaxel in platinum-resistant recurrent epithelial ovarian cancer.

Detailed Description

This is a phase II open label, non-randomized, study to evaluate the safety and efficacy of Ipatasertib (GDC-0068) in combination with paclitaxel in platinum-resistant recurrent epithelial ovarian cancer.

The primary objective of the study is to determine - the safety and objective response rate of treatment with ipatasertib (GDC-0068) in combination with paclitaxel in platinum-resistant recurrent epithelial ovarian cancer at week 12 for two cohorts of patients: with PI3K/AKT mutations (altered) and without PI3K/AKT mutations (non-altered)

About 39 patients will participate in the study and the accrual will take place over a course of 30 months Patients will be treated until disease progression and followed for 1 year thereafter.

The two drugs are ipatasertib and paclitaxel.

• Ipatasertib will be given 400mg PO daily: day 1-21 of 28 day cycle
• Paclitaxel will be given 80mg/m2 IV weekly: day 1, 8, 15 of 28 day cycle

The study hypothesis is that the combination of Ipatasertib (GDC-0068) plus paclitaxel will safely induce a tumor response and increase the objective response rate in patients with platinum-resistant recurrent epithelial ovarian cancer, with or without PI3K/AKT mutations.

This trial will enroll patients with platinum-resistant recurrent epithelial ovarian cancer. Given the relatively poor prognosis and limited treatment options for these patients, this population is considered appropriate for trials of novel therapeutic candidates. The benefit-risk ratio for ipatasertib in combination with paclitaxel is expected to be acceptable in this setting.

Conditions

Ovarian Neoplasms

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

PI3K/AKT mutations (altered)

Participants with recurrent epithelial ovarian cancer with PI3K/AKT mutations (altered)

Group Type: ACTIVE_COMPARATOR

Ipatasertib

Intervention Type: DRUG

400mg PO daily: day 1-21 of 28 day cycle

Paclitaxel

Intervention Type: DRUG

80 mg/m2 IV weekly: day 1, 8, 15 of 28 day cycle

Without PI3K/AKT mutations (non-altered)

Participants with recurrent epithelial ovarian cancer without PI3K/AKT mutations (non-altered)

Group Type: ACTIVE_COMPARATOR

Ipatasertib

Intervention Type: DRUG

400mg PO daily: day 1-21 of 28 day cycle

Paclitaxel

Intervention Type: DRUG

80 mg/m2 IV weekly: day 1, 8, 15 of 28 day cycle

Interventions

Ipatasertib

400mg PO daily: day 1-21 of 28 day cycle

Intervention Type: DRUG

Paclitaxel

80 mg/m2 IV weekly: day 1, 8, 15 of 28 day cycle

Intervention Type: DRUG

Other Intervention Names

GDC-0068

Eligibility Criteria

Inclusion Criteria

• Provision of signed and dated, written informed consent prior to any study specific procedures, sampling and analyses

o If a patient declines to participate in any voluntary exploratory research and/or genetic component of the study, there will be no penalty or loss of benefit to the patient and he/she will not be excluded from other aspects of the study

• Aged at least 18 years at time of signing informed consent
• A pathologic (histology or cytology) confirmed diagnosis of epithelial ovarian cancer, including fallopian or primary peritoneal cancer

o low grade serous histology is excluded

• Radiographic evidence of recurrent epithelial ovarian cancer (ovarian, fallopian tube, or primary peritoneal cancer) that has become "platinum-resistant," defined as progression of disease within 6 months from the last dose of platinum-based chemotherapy, or platinum refractory
• Not a candidate for cytoreductive surgery
• Measurable disease (at least one lesion that can be accurately assessed repeatedly by CT or MRI) as evidenced on pre-treatment baseline CT of Chest/Abdomen/Pelvis, MRI, or PET/CT, or evaluable disease (defined as anything non-measurable- pleural effusions, lesions <1cm, etc).
• World Health Organization (WHO) performance status 0-1 with no deterioration over the previous 2 weeks and minimum life expectancy of 12 weeks
• Up to 3 lines of prior cytotoxic chemotherapy
• Previously received bevacizumab
• Has not received weekly paclitaxel-containing regimen, EXCEPT for in the front-line setting

o Patients with prior paclitaxel reactions may be enrolled if they have been successfully re-treated with steroid pre-medication in the past

• Patients must use adequate contraceptive measures, should not be breast feeding and must have a negative pregnancy test prior to start of dosing (within 7 days) if of child-bearing potential or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening:

• Post-menopausal defined as aged more than 50 years and amenorrhea for at least 12 months following cessation of all exogenous hormonal treatments
• Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods with a failure rate of < 1% per year during the treatment period and for 28 days after the last dose of study treatment. Women must refrain from donating eggs during this same period.

Exclusion Criteria

• Treatment with any of the following:

• Any investigational agents or study drugs from a previous clinical study within 28 days of the first dose of study treatment
• Any other chemotherapy, immunotherapy or anticancer agents within 14 days of the first dose of study treatment
• Potent inhibitors or inducers or substrates of CYP3A4 or substrates of CYP2D6 within 2 weeks before the first dose of study treatment (3 weeks for St John's Wort)
• Any prior exposure to Ipatasertib
• Major surgery (excluding placement of vascular access) within 4 weeks of the first dose of study treatment
• Radiotherapy with a wide field of radiation within 4 weeks or radiotherapy with a limited field of radiation for palliation within 2 weeks of the first dose of study treatment
• With the exception of alopecia, any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) grade 1 at the time of starting study treatment
• Spinal cord compression or brain metastases unless asymptomatic, treated and stable and not requiring steroids for at least 2 weeks prior to start of study treatment
• Concurrent use of endocrine therapy
• As judged by the investigator, any evidence of severe or uncontrolled systemic diseases, including active bleeding diatheses, or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV). Screening for chronic conditions is not required.
• Any of the following cardiac criteria:

• Any clinically important abnormalities in rhythm, known prolonged QTc, conduction or morphology of resting ECG, complete left bundle branch block, third degree heart block
• Experience of any of the following procedures or conditions in the preceding 6 months: coronary artery bypass graft, angioplasty, vascular stent, myocardial infarction, angina pectoris, congestive heart failure NYHA Grade 2 or greater
• Uncontrolled hypotension - Systolic BP <90mmHg and/or diastolic BP <50mmHg
• Left ventricular ejection fraction (LVEF) below lower limit of normal for site
• Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values:

• Absolute neutrophil count < 1.5 x 109/L
• Platelet count < 100 x 109/L
• Hemoglobin < 9 g/L
• Alanine aminotransferase > 2.5 times the upper limit of normal (ULN)
• Aspartate aminotransferase > 2.5 times ULN
• Total bilirubin > 1.5 times ULN
• Creatinine >1.5 times ULN concurrent with creatinine clearance < 50 ml/min (measured or calculated by Cockcroft and Gault equation); confirmation of creatinine clearance is only required when creatinine is > 1.5 times ULN
• Proteinuria 3+ on dipstick analysis or >500mg/24 hours
• Sodium or potassium outside normal reference range for site
• Peripheral neuropathy grade 2 or greater
• Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption Ipatasertib
• History of hypersensitivity to Ipatasertib, or drugs with a similar chemical structure or class to Ipatasertib
• Clinically significant abnormalities of glucose metabolism as defined by any of the following:

• Diagnosis of type I or type II diabetes mellitus requiring insulin
• A baseline fasting glucose value of ≥ 200 mg/dL (fasting glucose value to be obtained only if non-fasting glucose >200mg/dL)
• Glycosylated hemoglobin (HbA1C) >7.5%
• Uncontrolled pleural effusion, pericardial effusion, or ascites
• Other malignancies within the past 3 years, with the exception of adequately resected basal or squamous carcinoma of the skin
• Clinically significant pulmonary symptoms or disease
• Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Icahn School of Medicine at Mount Sinai

OTHER

Sponsor Role: lead

Responsible Party

Amy Tiersten

Professor - Hematology Oncology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Amy Tiersten, MD

Role: PRINCIPAL_INVESTIGATOR

Icahn School of Medicine at Mount Sinai

Locations

Dubin Breast Center

New York, New York, United States

Countries

United States

Other Identifiers

GCO 19-2707

Identifier Type: -

Identifier Source: org_study_id