A Study Evaluating the Safety, Pharmacokinetics and Efficacy of Ipatasertib Administered in Combination With Rucaparib in Participants With Advanced Breast, Ovarian Cancer, and Prostate Cancer.

NCT03840200 | Completed Phase 1 Results FDA Drug

• 1 other identifier: BO40933
• Study Type: interventional
• Target: 51
• Locations: 5 countries
• Sites: 17

Brief Summary

This is a study in participants with advanced breast, ovarian, or prostate cancer to investigate the dose, safety, pharmacokinetics, and preliminary efficacy of ipatasertib in combination with rucaparib. The study consists of two parts: a Dose-Escalation Phase (Part 1) in participants with previously treated advanced breast cancer, ovarian cancer, or prostate cancer and a Dose-Expansion Phase (Part 2) in participants with advanced prostate cancer who have had at least one line of prior therapy with second-generation androgen-receptor (AR)-targeted agents (e.g., abiraterone, enzalutamide, apalutamide).

Conditions

Breast Cancer; Prostate Cancer; Ovarian Cancer

Outcome Measures

Primary Outcomes (3)

• Percentage of Participants With Adverse Events

  An adverse event (AE) was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product.

  From Baseline up until 90 days after the last dose of study drug (up to 2 years)

• Dose Escalation: Percentage of Participants With Dose-Limiting Toxicities (DLTs) That Determine the Maximum-Tolerated Dose (MTD) of the Ipatasertib and Rucaparib Combination

  A DLT was defined as adverse events related to study treatments occurring during the DLT reporting period, which included: any death related to study treatment; grade 4 neutropenia lasting for ≥7 days; grade ≥3 neutropenia complicated by fever ≥38°C or infection; grade 4 thrombocytopenia lasting for ≥7 days; grade ≥3 thrombocytopenia complicated by hemorrhage or that requires transfusion; study treatment-related grade ≥3 non-hematologic toxicity graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5 (NCI CTCAE, v5.0).

  Day -7 to Day 28 of Cycle 1 (1 cycle = 28 days) (up to 35 days)

• Percentage of Participants With Prostate-Specific Antigen Response (PSAR)

  PSA response was defined as the percentage of participants with a reduction in the PSA level of 50% or more. PSA response analysis was based on central PSA measurement. The 95% CI was estimated using the Clopper-Pearson method.

  From Baseline up to 1.5 years

Secondary Outcomes (7)

• Percentage of Participants With Objective Response, as Assessed by Investigator Based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v.1.1)

  From Baseline up to 1.5 years (assessed at the end of Cycle 2,4,6, and every 3 cycles thereafter up to progression, 1 cycle= 28 days)

• Duration of Objective Response in Participants With Measurable Disease at Baseline, as Assessed by Investigator Based on RECIST v1.1

  From Baseline up to 1.5 years (assessed at the end of Cycle 2,4,6, and every 3 cycles thereafter up to progression, 1 cycle= 28 days)

• Radiographic Progression Free Survival (rPFS), as Assessed by Prostate Cancer Working Group 3 Criteria (PCWG3)

  From Baseline up to 1.5 years (assessed at the end of Cycle 2,4,6, and every 3 cycles thereafter up to progression, 1 cycle= 28 days)

• Overall Survival (OS) in All Participants

  From Baseline to death from any cause, assessed up to 2 years

• Plasma Concentration of Ipatasertib

  Dose Escalation: Cycle 1: Day 1 and 15 (1, 2 ,3, 5 hours post-dose), Day 15 (Predose) and Cycle 2: Day 1 and 15 (Predose); Dose Expansion: Cycle 1: Day 15 (Predose) and Cycle 2: Day 1 and 15 (Predose) (1 cycle = 28 days)

Study Arms (5)

Dose escalation-Cohort 1

EXPERIMENTAL

Participants with advanced breast cancer, ovarian cancer, or prostate cancer will receive ipatasertib, 300 milligrams (mg), orally, once daily (QD) for 7 days in the run-in period. Participants will then receive ipatasertib, 300 mg, orally QD, and rucaparib, 400 mg, orally twice daily (BID) in each 28-day cycle until disease progression, unacceptable toxicity, death, or participant or investigator's decision to withdraw, whichever occurs first.

Drug: Ipatasertib; Drug: Rucaparib

Dose escalation-Cohort 2a

EXPERIMENTAL

Participants with advanced breast cancer, ovarian cancer, or prostate cancer will receive ipatasertib, 300 mg, orally, QD for 7 days in the run-in period. Participants will then receive ipatasertib, 300 mg, orally QD, and rucaparib, 600 mg, orally BID in each 28-day cycle until disease progression, unacceptable toxicity, death, or participant or investigator's decision to withdraw, whichever occurs first.

Drug: Ipatasertib; Drug: Rucaparib

Dose escalation-Cohort 2b

EXPERIMENTAL

Participants with advanced breast cancer, ovarian cancer, or prostate cancer will receive ipatasertib, 400 mg, orally, QD for 7 days in the run-in period. Participants will then receive ipatasertib, 400 mg, orally QD, and rucaparib, 400 mg, orally BID in each 28-day cycle until disease progression, unacceptable toxicity, death, or participant or investigator's decision to withdraw, whichever occurs first.

Drug: Ipatasertib; Drug: Rucaparib

Dose escalation-Cohort 3

EXPERIMENTAL

Participants with advanced breast cancer, ovarian cancer, or prostate cancer are planned to receive ipatasertib 400 mg orally QD for 7 days (run-in period prior to Cycle 1). Participants will then receive ipatasertib 400 mg orally QD and rucaparib 600 mg, orally BID in 28 days cycle until disease progression, unacceptable toxicity, death, or participant or investigator's decision to withdraw, whichever occurs first.

Drug: Ipatasertib; Drug: Rucaparib

Dose Expansion

EXPERIMENTAL

The recommended dose (ipatasertib and rucaparib) identified in Part 1 will be evaluated in participants with advanced prostate cancer who have had at least one line of prior therapy with second-generation androgen-receptor (AR)-targeted agents (e.g., abiraterone, enzalutamide, apalutamide).

Drug: Ipatasertib; Drug: Rucaparib

Interventions

Ipatasertib DRUG

Ipatasertib will be administered orally.

Also known as: RO5532961, GDC-0068

Dose Expansion; Dose escalation-Cohort 1; Dose escalation-Cohort 2a; Dose escalation-Cohort 2b; Dose escalation-Cohort 3

Rucaparib DRUG

Rucaparib will be administered orally.

Also known as: CO-338

Dose Expansion; Dose escalation-Cohort 1; Dose escalation-Cohort 2a; Dose escalation-Cohort 2b; Dose escalation-Cohort 3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• A life expectancy of at least 3 months
• Ability to swallow oral study drug
• Have adequate organ and marrow function as confirmed by the laboratory values listed below, obtained within 28 days prior to the first dose of study treatment:
• Bone marrow function assessments (without transfusion within 28 days prior to receipt of study treatment):
• ANC \>= 1500 cells/uL (1.5 x 10\^9/L) without granulocyte-colony stimulating factor support
• Platelet count \>= 100.0 x 10\^9/L
• Hemoglobin \>= 9 g/dL (or 5.6 mmol/L)
• Chemistry panel assessments:
• AST and ALT \<= 1.5 x upper limit of normal (ULN); if liver metastases, \<= 2.5 x ULN
• Bilirubin \<= 1.5 x ULN (\<= 3 x ULN if hyperbilirubinemia is due to Gilbert's syndrome)
• Serum albumin \>= 3.0 g/dL
• Serum creatinine \<= 1.5 x ULN or creatinine clearance \>= 50 mL/min
• Fasting glucose \<= 150 mg/dL and hemoglobin A1c \<= 7.5%
• Resolved or stabilized toxicities resulting from previous therapy to Grade 1 (except for alopecia and neuropathy).

You may not qualify if:

• Pregnant or breastfeeding, or intending to become pregnant during the study or within 28 days after the final dose of ipatasertib or 6 months after the final dose of rucaparib
• Prior treatment with a PARP inhibitor, AKT inhibitor, or PI3K inhibitor
• Treatment with investigational therapy within 14 days prior to initiation of study drug
• Symptomatic and/or untreated CNS metastases
• Uncontrolled tumor-related pain
• Non-study-related minor surgical procedures \<= 5 days or major (invasive) surgical procedure \<=14 days prior to first dose of study treatment
• Patients with active hepatitis C virus (HCV)
• Hepatitis B virus (HBV) infection (chronic or acute), defined as having a positive hepatitis B surface antigen (HBsAg) test or a positive quantitative HBV DNA test
• Known HIV infection
• Illicit drug or alcohol abuse within 12 months prior to screening, in the investigator's judgment
• Malabsorption syndrome or other condition that would interfere with enteral absorption
• Serious infection requiring antibiotics within 14 days of first dose of study treatment
• Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study
• Need for chronic corticosteroid therapy of \>= 10 mg of prednisone per day or an equivalent dose of other anti-inflammatory corticosteroids or immunosuppressants for a chronic disease
• History of another malignancy within 5 years prior to randomization, except for either adequately treated non-melanomatous carcinoma of the skin, adequately treated melanoma in situ, adequately treated non-muscle-invasive urothelial carcinoma of the bladder (Tis, Ta, and low-grade T1 tumors), or other malignancies where the patient has undergone potentially curative therapy with no evidence of disease and are deemed by the treating physician to have a recurrence rate of \< 5% at 5 years.

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (17)

California Cancer Associates for Research & Excellence, Inc.

San Marcos, California, 92069, United States

Location

Regional Cancer Care Associates LLC, Central Jersey Division

East Brunswick, New Jersey, 08816, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Mary Crowley Medical Research Center; Oncology

Dallas, Texas, 75246, United States

Location

Kinghorn Cancer Centre; St Vincents Hospital

Darlinghurst, New South Wales, 2010, Australia

Location

Macquarie University Hospital

Macquarie Park, New South Wales, 2109, Australia

Location

Cabrini Hospital Malvern

Malvern, Victoria, 3144, Australia

Location

Istituto Nazionale Tumori Regina Elena IRCCS

Rome, Lazio, 00144, Italy

Location

Fondazione IRCCS Istituto Nazionale dei Tumori; S. C. Oncologia Medica 2

Milan, Lombardy, 20133, Italy

Location

Azienda Ospedaliera Santa Maria di Terni

Terni, Umbria, 20089, Italy

Location

Istituto Oncologico Veneto IRCCS

Padua, Veneto, 35128, Italy

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Severance Hospital, Yonsei University

Seoul, 03722, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Clínica Universidad de Navarra

Pamplona, Navarre, 31620, Spain

Location

Vall d?Hebron Institute of Oncology (VHIO), Barcelona

Barcelona, 08035, Spain

Location

Hospital Universitario Virgen de la Victoria

Málaga, 29010, Spain

Location

Related Publications (1)

• Pook D, Geynisman DM, Carles J, de Braud F, Joshua AM, Perez-Gracia JL, Llacer Perez C, Shin SJ, Fang B, Barve M, Maruzzo M, Bracarda S, Kim M, Kerloeguen Y, Gallo JD, Maund SL, Harris A, Huang KC, Poon V, Sutaria DS, Gurney H. A Phase Ib, Open-label Study Evaluating the Safety and Efficacy of Ipatasertib plus Rucaparib in Patients with Metastatic Castration-resistant Prostate Cancer. Clin Cancer Res. 2023 Sep 1;29(17):3292-3300. doi: 10.1158/1078-0432.CCR-22-2585.

  PMID: 37339186 DERIVED

MeSH Terms

Conditions

Breast Neoplasms; Prostatic Neoplasms; Ovarian Neoplasms

Interventions

ipatasertib; rucaparib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Genital Neoplasms, Female; Endocrine System Diseases; Gonadal Disorders

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 11, 2019
• First Posted: February 15, 2019
• Study Start: June 12, 2019
• Primary Completion: December 7, 2021
• Study Completion: January 4, 2022
• Last Updated: October 30, 2023
• Results First Posted: October 30, 2023

Record last verified: 2023-10

Locations

IT (4); KR (3); AU (3); US (4); ES (3)