Castration-Resistant Prostatic CancerPhase 1NCT04404140
A Study Evaluating The Safety, Efficacy and Pharmacokinetics Of Ipatasertib In Combination With Atezolizumab And Docetaxel In Metastatic Castration-Resistant Prostate Cancer (mCRPC).
A Phase 1 study testing Ipatasertib, Atezolizumab and Docetaxel in people with Castration-Resistant Prostatic Cancer, run by Hoffmann-La Roche at 9 sites in 4 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Castration-Resistant Prostatic Cancer
- What is being tested?
- Ipatasertib, Atezolizumab and Docetaxel
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 9 sitesin 4 countries
- Study dates
- 9 Jul 2020to 14 Oct 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
- Serious infection requiring antibiotics within 14 days prior to the first dose of study treatment.
- Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the participant's safe participation in and completion of the study.
- History of another malignancy within 5 years prior to enrollment.
- History of clinically significant cardiovascular dysfunction.
- Presence of any other condition, metabolic dysfunction, physical examination finding, or laboratory finding that may increase the risk associated with study participation or may interfere with the interpretation of study results and in the opinion of the investigator, would make the participant inappropriate for study entry.
- Ipatasertib-Specific Exclusion Criteria:
- Type 1 or Type 2 diabetes mellitus requiring insulin at study entry.
- History of inflammatory bowel disease (e.g., Crohn disease and ulcerative colitis) or active bowel inflammation (e.g., diverticulitis).
- Grade >= 2 uncontrolled or untreated hypercholesterolemia or hypertriglyceridemia.
- Treatment with strong CYP3A inhibitor or strong CYP3A inducer within 2 weeks or 5 drug-elimination half-lives of this treatment (whichever is longer) prior to initiation of study drug.
- Atezolizumab-Specific Exclusion Criteria:
- Active or history of autoimmune disease or immune deficiency.
- History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan.
- Prior allogeneic stem cell or solid organ transplantation.
- Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during treatment with atezolizumab or within 5 months after the last dose of atezolizumab.
- History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins.
- Known hypersensitivity to Chinese hamster ovary cell products or recombinant human antibodies.
- Treatment with systemic immunostimulatory agents within 4 weeks or 5 drug-elimination half-lives of the drug (whichever is longer) prior to initiation of study treatment.
- 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.
- Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during the course of the study.
- Docetaxel-Specific Exclusion Criteria:
- Known hypersensitivity or contraindication to any component of docetaxel, including its excipient polysorbate 80.
- Grade >= 2 peripheral neuropathy.
Trial locations and contacts
9 sites in 4 countries.
9 sites in 4 countries
France4 sites
HOPITAL JEAN MINJOZ; Oncologie
Besançon, 25030
Centre Val Aurelle Paul Lamarque; Radiotherapie
Montpellier, 34928
Hopital d'Instruction des Armees de Begin
Saint-Mandé, 94160
Gustave Roussy
Villejuif, 94805
Spain2 sites
Institut Catala d Oncologia Hospital Duran i Reynals
Barcelona, 08908
Hospital Ramon y Cajal; Servicio de Oncologia
Madrid, 28034
Switzerland2 sites
Kantonsspital Graubünden Medizin Onkologie; Onkologie und Hämatologie
Chur, 7000
UniversitätsSpital Zürich; Zentrum für Hämatologie und Onkologie, Klinik für Onkologie
Zurich, 8091
Italy1 site
Fondazione IRCCS Istituto Nazionale dei Tumori
Milan, Lombardy, 20133
About this study
Official title: A Phase Ib, Open-Label, Multicenter Study Evaluating The Safety, Efficacy and Pharmacokinetics Of Ipatasertib In Combination With Atezolizumab And Docetaxel In Metastatic Castration-Resistant Prostate Cancer.
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
- Being tested
- Ipatasertib, Atezolizumab, Docetaxel
- Medical subject headings
- Prostatic Neoplasms, Castration-Resistant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IpatasertibDrug
Ipatasertib will be administered at a dose of 400 mg, as per the dosing schedule described above.
AtezolizumabDrug
Atezolizumab will be administered at a fixed dose of 1200 mg, as per the dosing schedule described above.
DocetaxelDrug
Docetaxel will be administered at a dose of 75 mg/m^2, as per the dosing schedule described above.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Ipatasertib; Drug: Atezolizumab; Drug: Docetaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 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
Measured: 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)
Measured: Up to 35 months
Secondary outcomes (8)
Time to PSA Progression
Measured: Up to 35 months
radiographic Progression-Free Survival (rPFS)
Assessed according to the Prostate Cancer Working Group 3 (PCWG3) criteria
Measured: Up to 35 months
Overall Survival (OS) (median OS and landmark survival at 12, 18 and 24 months)
Measured: Up to 35 months
Documented Objective Response (DOR) (In participants presenting with measurable visceral disease or measurable extrapelvic adenopathy at baseline)
Defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1
Measured: Up to 35 months
Clinical Benefit Rate (CBR) (In participants presenting with measurable visceral disease or measurable extrapelvic adenopathy at baseline)
Defined as the proportion of participants who have an objective response (a CR or a PR) or stable disease for at least 27 weeks, as determined by the Investigator according to RECIST v1.1 and PCWG3 criteria
Measured: Up to 35 months
Plasma Concentrations (ng/mL) of Ipatasertib and G-037720 at pre-specified timepoints
Measured: Up to 35 months
Serum Concentrations (ng/mL) of Atezolizumab at pre-specified timepoints
Measured: Up to 35 months
Percentage of Participants with Anti-Drug Antibodies (ADAs) to Atezolizumab
Measured: Up to 35 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 May 2020
- Study start9 Jul 2020
- Primary completion14 Oct 2022
- Study completion14 Oct 2022
Why it stopped: Despite many risk-minimization strategies, the combination of ipatasertib, atezolizumab and docetaxel was challenging due to multiple study treatment modifications required to manage toxicity, making further enrollment inappropriate.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Castration-Resistant Prostatic CancerStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04404140
- Sponsor's protocol ID
- CO41792
- Other IDs
- 2019-004591-19, 2019
- Status last verified
- Oct 2023
- First submitted
- 15 May 2020
- Last updated
- 17 Oct 2023
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib, Open-Label, Multicenter Study Evaluating The Safety, Efficacy and Pharmacokinetics Of Ipatasertib In Combination With Atezolizumab And Docetaxel In Metastatic Castration-Resistant Prostate Cancer.
- ClinicalTrials.gov ID
- NCT04404140
- Acronym / sponsor ID
- CO41792
- Conditions
- Castration-Resistant Prostatic Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Despite many risk-minimization strategies, the combination of ipatasertib, atezolizumab and docetaxel was challenging due to multiple study treatment modifications required to manage toxicity, making further enrollment inappropriate.
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- 9 Jul 2020 (actual)
- Primary completion
- 14 Oct 2022 (actual)
- Study completion
- 14 Oct 2022 (actual)
- First posted
- 27 May 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ipatasertib + Atezolizumab + Docetaxel | Experimental | Drug: Ipatasertib, Drug: Atezolizumab, Drug: DocetaxelPart 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 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.
Key exclusion criteria (38 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IpatasertibIpatasertib will be administered at a dose of 400 mg, as per the dosing schedule described above. | Drug | Ipatasertib + Atezolizumab + Docetaxel |
| AtezolizumabAtezolizumab will be administered at a fixed dose of 1200 mg, as per the dosing schedule described above. | Drug | Ipatasertib + Atezolizumab + Docetaxel |
| DocetaxelDocetaxel will be administered at a dose of 75 mg/m^2, as per the dosing schedule described above. | Drug | Ipatasertib + Atezolizumab + Docetaxel |
Primary outcome
Percentage of Participants with Adverse Events (AEs)
Time frame: Up to 35 months
Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0)
Confirmed Prostate Specific Antigen (PSA) Response
Time frame: Up to 35 months
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
Overall Response Rate (ORR) (In participants presenting with measurable visceral disease or measurable extrapelvic adenopathy at baseline)
Time frame: Up to 35 months
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)
8 secondary outcomes
Time to PSA Progression
Time frame: Up to 35 months
radiographic Progression-Free Survival (rPFS)
Time frame: Up to 35 months
Overall Survival (OS) (median OS and landmark survival at 12, 18 and 24 months)
Time frame: Up to 35 months
Documented Objective Response (DOR) (In participants presenting with measurable visceral disease or measurable extrapelvic adenopathy at baseline)
Time frame: Up to 35 months
Clinical Benefit Rate (CBR) (In participants presenting with measurable visceral disease or measurable extrapelvic adenopathy at baseline)
Time frame: Up to 35 months
Plasma Concentrations (ng/mL) of Ipatasertib and G-037720 at pre-specified timepoints
Time frame: Up to 35 months
Serum Concentrations (ng/mL) of Atezolizumab at pre-specified timepoints
Time frame: Up to 35 months
Percentage of Participants with Anti-Drug Antibodies (ADAs) to Atezolizumab
Time frame: Up to 35 months
Results and safety
The study was stopped early (reason given: Despite many risk-minimization strategies, the combination of ipatasertib, atezolizumab and docetaxel was challenging due to multiple study treatment modifications required to manage toxicity, making further enrollment inappropriate.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Oct 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trials study director
Hoffmann-La Roche
9 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ipatasertib, Atezolizumab and Docetaxel in people with Castration-Resistant Prostatic Cancer, run by Hoffmann-La Roche at 9 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 38 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 17 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in France, Spain, Switzerland, Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Despite many risk-minimization strategies, the combination of ipatasertib, atezolizumab and docetaxel was challenging due to multiple study treatment modifications required to manage toxicity, making further enrollment inappropriate.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants with Adverse Events (AEs) (time frame: Up to 35 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Oct 2023.