Status:
COMPLETED
A Study to Evaluate the Safety and Efficacy of Ipatasertib in Combination With Atezolizumab and Paclitaxel or Nab-Paclitaxel in Participants With Locally Advanced or Metastatic Triple-Negative Breast Cancer
Lead Sponsor:
Hoffmann-La Roche
Conditions:
Breast Cancer
Eligibility:
All Genders
18+ years
Phase:
PHASE1
Brief Summary
This is a study consisting of four cohorts in this setting. In Cohort 1, the safety and efficacy of ipatasertib (ipat) in combination with atezolizumab (atezo) and paclitaxel (pac) or nab-paclitaxel w...
Eligibility Criteria
Inclusion
- General:
- Eastern Cooperative Oncology Group Performance Status of 0 or 1.
- Adequate hematologic and organ function.
- For Cohorts 1, 2 and 4: Life expectancy of at least 6 months.
- For men and women of child bearing potential: agreement to remain abstinent or use protocol defined contraceptive measures during the treatment period and for at least 28 days after the last dose of ipatasertib, 6 months after the last dose of paclitaxel, nab-paclitaxel, or doxorubicin, and 12 months after the last dose of cyclophosphamide, and 5 months after the last dose of atezolizumab, whichever occurs later along with refraining from donating sperm or eggs during this same period.
- Disease-specific:
- For Cohorts 1, 2 and 4: histologically documented TNBC that is locally advanced or metastatic and is not amenable to resection with curative intent.
- For Cohort 2: disease progression following one or two lines of systemic therapy for inoperable locally advanced or metastatic TNBC.
- For Cohorts 1, 2 and 4: measurable disease according to RECIST v1.1 criteria.
- For Cohort 2: Treated brain or spinal cord metastases are allowed if participants have stable disease and are not on steroid treatment.
- For Cohort 3: histologically documented TNBC with a primary breast tumour size of \> 2 cm by at least one radiographic or clinical measurement and disease stage at presentation of cT2-4 cN0-3 cM0.
- For Cohort 3: participant agreement to undergo appropriate surgical management, including axillary lymph node surgery and partial or total mastectomy, after completion of neoadjuvant treatment.
- For Cohort 4: participants must have centrally confirmed PD-L1-positive tumour.
Exclusion
- General:
- History of malabsorption syndrome or other condition that would interfere with enteral absorption or results in the inability or unwillingness to swallow pills.
- Active infection requiring antibiotics.
- History of or current evidence of HIV infection.
- Known clinically significant history of liver disease.
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1 of Cycle 1 or anticipation of need for a major surgical procedure (other than anticipated breast surgery for Cohort 3) during the course of the study.
- Pregnant or breastfeeding.
- New York Heart Association (NYHA) Class II, III, or IV heart failure; left ventricular ejection fraction \< 50%; or active ventricular arrhythmia requiring medication.
- Treatment with approved or investigational cancer therapy within 14 days prior to Day 1 of Cycle 1.
- Prior treatment with an Akt inhibitor.
- Disease-specific:
- For Cohorts 1 and 4: history of or known presence of brain or spinal cord metastases.
- For Cohorts 1 and 4: participants who have received previous systemic therapy for inoperable locally advanced or metastatic TNBC, including chemotherapy, immune checkpoint inhibitors, or targeted agents.
- Unresolved, clinically significant toxicity from prior therapy, except for alopecia and Grade 1 peripheral neuropathy.
- Participants who have received palliative radiation treatment to peripheral sites (e.g., bone metastases) for pain control and whose last treatment was completed 14 days prior to Day 1 of Cycle 1 and have recovered from all acute, reversible effects.
- Uncontrolled pleural effusion, pericardial effusion, or ascites.
- Uncontrolled tumor related complications.
- Uncontrolled hypercalcaemia or symptomatic hypercalcaemia requiring continued use of bisphosphonate therapy.
- Malignancies other than breast cancer within 5 years prior to Day 1 of Cycle 1.
- For Cohort 3, participants with the following are excluded: \[1\] prior history of invasive breast cancer; \[2\] prior systemic therapy for treatment and/or prevention of invasive breast cancer; \[3\] previous therapy with anthracyclines or taxanes for any malignancy; \[4\] bilateral breast cancer; \[5\] undergone incisional and/or excisional biopsy of primary tumor and/or axillary lymph nodes; \[6\] undergone axillary lymph node dissection (ALND) prior to initiation of neoadjuvant therapy; \[6\] history of other malignancy within 5 years prior to screening; \[7\] history of cerebrovascular accident within 12 months prior to initiation of study treatment; \[8\] cardiopulmonary dysfunction; \[9\] known allergy or hypersensitivity to the components of cyclophosphamide/doxorubicin formulations and filgrastim or pegfilgrastim formulations; \[10\] severe infection within 4 weeks prior to initiation of study treatment; \[11\] treatment with therapeutic oral or IV (Intravenous) antibiotics within 2 weeks prior to initiation of study treatment and \[12\] prior treatment with CD137 agonists or immune checkpoint - blockade therapies.
- Ipatasertib-specific:
- History of Type I or Type II diabetes mellitus requiring insulin.
- Grade \>= 2 uncontrolled or untreated hypercholesterolemia or hypertriglyceridemia.
- History of or active inflammatory bowel disease or active bowel inflammation.
- Clinically significant lung disease.
- Treatment with strong CYP3A inhibitors or strong CYP3A inducers.
- Atezolizumab-specific:
- 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 hypersensitivity reactions to study drug or any component of the study drug formulation.
- Treatment with systemic immunostimulatory agents and immunosuppressive medication treatment, or anticipation of need for systemic immunosuppressive medication during the course of the study.
- Paclitaxel-specific:
- \- Grade \>= 2 peripheral neuropathy.
Key Trial Info
Start Date :
February 13 2018
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
March 16 2022
Estimated Enrollment :
139 Patients enrolled
Trial Details
Trial ID
NCT03800836
Start Date
February 13 2018
End Date
March 16 2022
Last Update
October 30 2024
Active Locations (18)
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1
Pacific Shores Medical Group
Long Beach, California, United States, 90813
2
St Vincents Hospital; Cardiopulmonary transplant Ambulatory Care Dept
Darlinghurst, New South Wales, Australia, 2010
3
Austin Hospital
Heidelberg, Victoria, Australia, 3084
4
Peter MacCallum Cancer Center
North Melbourne, Victoria, Australia, 3051