Overview

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

Status:
Withdrawn
Trial end date:
2023-10-01
Target enrollment:
0
Participant gender:
Female
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.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Icahn School of Medicine at Mount Sinai
Treatments:
Paclitaxel
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