A Study Evaluating The Safety, Efficacy and Pharmacokinetics Of Ipatasertib In Combination With Atezolizumab And Docetaxel In Metastatic Castration-Resistant Prostate Cancer (mCRPC).

NCT04404140 | Terminated Phase 1 FDA Drug

• 2 other identifiers: CO417922019-004591-19
• Study Type: interventional
• Target: 6
• Locations: 4 countries
• Sites: 9

Brief Summary

A study evaluating the safety, preliminary efficacy and pharmacokinetics of ipatasertib in combination with atezolizumab and docetaxel in participants with mCRPC previously treated with second-generation AR (Androgen Receptor)-targeted therapy. The study consists of two parts: \[1\] Part A: Safety run-in cohort of approximately 12 participants; \[2\] Part B: Expansion cohort of approximately 38 participants. All participants in this study will continue to be treated until progression of disease, loss of clinical benefit, unacceptable toxicity or withdrawal of consent.

Conditions

Castration-Resistant Prostatic Cancer

Outcome Measures

Primary Outcomes (3)

• Percentage of Participants with Adverse Events (AEs)

  Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0)

  Up to 35 months

• Confirmed Prostate Specific Antigen (PSA) Response

  Defined as the proportion of participants with a reduction in their PSA levels of 50% or more from baseline, confirmed by a second evaluation at least 3 weeks later

  Up to 35 months

• Overall Response Rate (ORR) (In participants presenting with measurable visceral disease or measurable extrapelvic adenopathy at baseline)

  Defined as the proportion of participants with a complete response (CR) or partial response (PR) on two consecutive occasions \>= 4 weeks apart, as determined by the Investigator according to RECIST v1.1 (Response Evaluation Criteria in Solid Tumors, Version 1.1)

  Up to 35 months

Secondary Outcomes (8)

• Time to PSA Progression

  Up to 35 months

• radiographic Progression-Free Survival (rPFS)

  Up to 35 months

• Overall Survival (OS) (median OS and landmark survival at 12, 18 and 24 months)

  Up to 35 months

• Documented Objective Response (DOR) (In participants presenting with measurable visceral disease or measurable extrapelvic adenopathy at baseline)

  Up to 35 months

• Clinical Benefit Rate (CBR) (In participants presenting with measurable visceral disease or measurable extrapelvic adenopathy at baseline)

  Up to 35 months

Study Arms (1)

Ipatasertib + Atezolizumab + Docetaxel

EXPERIMENTAL

Part A (Safety Run-In): 12 Participants will be administered Ipatasertib orally once a day \[QD\] from Day 1 to Day 14 in combination with Atezolizumab administered by intravenous (IV infusion) every 3 weeks (Q3W) on Day 1 of each cycle (a cycle being 21 days) and Docetaxel administered by IV infusion (Q3W) on Day 1 of each cycle. Docetaxel will be administered for a maximum of 10 cycles (approximately 7 months), after which Atezolizumab and Ipatasertib will be administered as a doublet until disease progression. During Part A, a staggered recruitment will be applied to the first and potentially first 6 participants to enrol a participant only once the former one has safely overcome the safety time window (Cycle 1). Part B (Expansion): 38 Participants will be administered Ipatasertib, Atezolizumab and Docetaxel as described above, though without a staggered enrolment or safety assessment window.

Drug: Ipatasertib; Drug: Atezolizumab; Drug: Docetaxel

Interventions

Ipatasertib DRUG

Ipatasertib will be administered at a dose of 400 mg, as per the dosing schedule described above.

Ipatasertib + Atezolizumab + Docetaxel

Atezolizumab DRUG

Atezolizumab will be administered at a fixed dose of 1200 mg, as per the dosing schedule described above.

Ipatasertib + Atezolizumab + Docetaxel

Docetaxel DRUG

Docetaxel will be administered at a dose of 75 mg/m\^2, as per the dosing schedule described above.

Ipatasertib + Atezolizumab + Docetaxel

Eligibility Criteria

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

You may qualify if:

• Ability to comply with the study protocol.
• Adenocarcinoma of the prostate without small-cell or neuroendocrine features.
• Metastatic disease that cannot be treated with curative intent.
• Surgical or medical castration with testosterone serum level \< 50 ng/dL (1.7 nM).
• For participants treated with luteinizing hormone-releasing hormone analogs, initiation therapy \>= 4 weeks prior to the first dose of study treatment and continued therapy throughout study treatment.
• Progression of Prostate Cancer.
• Receipt of at least one prior line of second generation AR-targeted therapy.
• For participants in Part A of study: measurable visceral disease or measurable extrapelvic adenopathy per RECIST v1.1.
• For participants in Part B of study: either measurable visceral disease or measurable extrapelvic adenopathy by RECIST v1.1 or bone lesions by bone scan, or both.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
• Life expectancy of \>= 3 months.
• Ability to swallow oral study drug.
• Adequate organ and bone marrow function.
• Resolved or stabilized toxicities resulting from previous therapy to Grade 1 (except for alopecia and neuropathy).
• For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from donating sperm.

You may not qualify if:

• Prior treatment with an AKT, PI3K, or mTOR inhibitor.
• Prior treatment with radium or other therapeutic radiopharmaceuticals for prostate cancer.
• Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX-40, CD137).
• Prior treatment with docetaxel or another chemotherapy agent for mCRPC.
• Treatment with investigational therapy within 14 days prior to initiation of study drug.
• History or known presence of central nervous system metastases including leptomeningeal carcinomatosis.
• Uncontrolled tumor-related pain.
• Symptomatic lesions (e.g., bone metastases or metastases causing nerve impingement) amenable to palliative radiotherapy should be treated prior to enrollment.
• Asymptomatic metastatic lesions whose further growth would likely cause functional deficits or intractable pain (e.g., epidural metastasis that is not presently associated with spinal cord compression) should be considered for loco- regional therapy if appropriate prior to enrollment.
• Non-study-related minor surgical procedures =\< 5 days or major (invasive) surgical procedure =\< 28 days prior to the first dose of study treatment.
• Active Hepatitis B and C infection (HBV/HCV).
• Known HIV infection.
• Uncontrolled pleural effusion, pericardial effusion, or ascites.
• 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.

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (9)

HOPITAL JEAN MINJOZ; Oncologie

Besançon, 25030, France

Location

Centre Val Aurelle Paul Lamarque; Radiotherapie

Montpellier, 34928, France

Location

Hopital d'Instruction des Armees de Begin

Saint-Mandé, 94160, France

Location

Gustave Roussy

Villejuif, 94805, France

Location

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, Lombardy, 20133, Italy

Location

Institut Catala d Oncologia Hospital Duran i Reynals

Barcelona, 08908, Spain

Location

Hospital Ramon y Cajal; Servicio de Oncologia

Madrid, 28034, Spain

Location

Kantonsspital Graubünden Medizin Onkologie; Onkologie und Hämatologie

Chur, 7000, Switzerland

Location

UniversitätsSpital Zürich; Zentrum für Hämatologie und Onkologie, Klinik für Onkologie

Zurich, 8091, Switzerland

Location

MeSH Terms

Conditions

Prostatic Neoplasms, Castration-Resistant

Interventions

ipatasertib; atezolizumab; Docetaxel

Condition Hierarchy (Ancestors)

Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 15, 2020
• First Posted: May 27, 2020
• Study Start: July 9, 2020
• Primary Completion: October 14, 2022
• Study Completion: October 14, 2022
• Last Updated: October 17, 2023

Record last verified: 2023-10

Locations

ES (2); IT (1); CH (2); FR (4)