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

NCT04561817 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: GCO 19-2707
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Ovarian Neoplasms

Keywords

Platinum-resistant; Ovarian cancer; Ipatasertib; Paclitaxel; Recurrent

Outcome Measures

Primary Outcomes (3)

• Objective response rate (ORR)

  ORR will be measured by the percentage of patients whose cancer decreases in size on assessment. This will be measured as the sum of complete response and partial response.

  At the end of Cycle 1 (each cycle is 28 days)

• Objective response rate (ORR)

  ORR will be measured by the percentage of patients whose cancer decreases in size on assessment. This will be measured as the sum of complete response and partial response.

  At the end of Cycle 2 (each cycle is 28 days)

• Objective response rate (ORR)

  ORR will be measured by the percentage of patients whose cancer decreases in size on assessment. This will be measured as the sum of complete response and partial response.

  At the end of Cycle 3 (each cycle is 28 days)

Secondary Outcomes (4)

• Progression free survival (PFS)

  At the end of Cycle 1 (each cycle is 28 days)

• Progression free survival (PFS)

  At the end of Cycle 2 (each cycle is 28 days)

• Progression free survival (PFS)

  At the end of Cycle 3 (each cycle is 28 days)

• Disease control rate (DCR)

  average 24 weeks

Study Arms (2)

PI3K/AKT mutations (altered)

ACTIVE COMPARATOR

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

Drug: Ipatasertib; Drug: Paclitaxel

Without PI3K/AKT mutations (non-altered)

ACTIVE COMPARATOR

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

Drug: Ipatasertib; Drug: Paclitaxel

Interventions

Ipatasertib DRUG

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

Also known as: GDC-0068

PI3K/AKT mutations (altered); Without PI3K/AKT mutations (non-altered)

Paclitaxel DRUG

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

PI3K/AKT mutations (altered); Without PI3K/AKT mutations (non-altered)

Eligibility Criteria

• Age: 18 Years - 90 Years
• Gender Eligibility Details: A female with confirmed diagnosis of epithelial ovarian cancer, including fallopian or primary peritoneal cancer
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Icahn School of Medicine at Mount Sinai: lead

Study Sites (1)

Dubin Breast Center

New York, New York, 10029, United States

Location

MeSH Terms

Conditions

Ovarian Neoplasms; Recurrence

Interventions

ipatasertib; Paclitaxel

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Amy Tiersten, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor - Hematology Oncology

Model Details: For non-altered patients- An interim analysis is scheduled when the number of enrolled patients reaches 14. The research team will stop the trial for futility if 2 or less than 2 patients respond. When the total number of patients reaches the maximum sample size of 25, the research team will reject the null hypothesis and conclude that the treatment is promising if the number of responses are greater than 6; otherwise the research team will conclude that the treatment is not promising. For altered patients-An interim analysis is scheduled when the number of enrolled patients reaches 8. The research team will stop the entire trial of two cohorts for futility if 1 or less than 1 patients respond. When the total number of patients reaches the maximum sample size of 14, the research team will reject the null hypothesis and conclude that the treatment is promising

Study Record Dates

• First Submitted: September 8, 2020
• First Posted: September 24, 2020
• Study Start: October 1, 2020
• Primary Completion: October 1, 2022
• Study Completion: October 1, 2023
• Last Updated: October 6, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Beginning 3 months and ending 5 years following article publication.
• Access Criteria: Investigators whose proposed use of the data has been approved by an independent review committee (%8Dlearned intermediary%8E) identified for this purpose.To achieve aims in the approved proposal.information on Availability of data will be provided later

Locations

US (1)