A Study of Ipatasertib in Combination with Atezolizumab and Paclitaxel as a Treatment for Patients with Locally Advanced Unresectable or Metastatic Triple-Negative Breast Cancer

Phase 1

• Conditions: Metastatic triple-negative breast cancer (TNBC); MedDRA version: 20.0Level: LLTClassification code 10027475Term: Metastatic breast cancerSystem Organ Class: 100000004864; MedDRA version: 21.1Level: LLTClassification code 10072740Term: Locally advanced breast cancerSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2019-000810-12-IT
• Lead Sponsor: F. HOFFMANN - LA ROCHE LTD.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-06-15
• Last Update Posted: 12 March 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 1155

Inclusion Criteria

- Women or men, age >= 18 years
- Willingness and ability to complete all study-related assessments, including PRO assessments, in the investigator's judgment
- Measurable disease according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
- Eastern Cooperative Oncology Group Performance Status of 0 or 1
- Adequate hematologic and organ function within 14 days before the first study treatment on Day 1 of Cycle 1
- Life expectancy of at least 6 months
- For women of childbearing potential: agreement to remain abstinent or use contraception, and agreement to refrain from donating eggs, women must remain abstinent or use contraceptive methods with a failure rate of < 1% per year during the treatment period and for at least 28 days after the final dose of ipat/placebo, 5 months after the final dose of atezo /placebo, and 6 months after the final dose of pac, whichever occurs later
- For men: agreement to remain abstinent or use contraceptive methods, and agreement to refrain from donating sperm, with female partners of childbearing potential, men must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of < 1% per year during the treatment period and for 28 days after the final dose of ipat /placebo, or 6 months after the final dose of pac, whichever occurs later
- For any patients enrolled in the extended enrollment phase: patient is a current resident of mainland China, Hong Kong, or Taiwan, and of Chinese ancestry Disease-Specific Inclusion Criteria
Disease-Specific Inclusion Criteria
- Appropriate candidate for paclitaxel monotherapy if tumor PD-L1 status is unknown or non-positive; appropriate candidate for paclitaxel and atezolizumab if tumor PD-L1 status is positive
- Histologically documented triple-negative adenocarcinoma of the breast that is locally advanced or metastatic and is not amenable to resection with curative intent
- Submittal of a formalin-fixed, paraffin-embedded tumor tissue block or a minimum of 15 freshly cut unstained, serial tumor slides from the most recently collected tumor tissue. Cytologic or fine-needle aspiration samples are not acceptable. Tumor tissue from bone metastases that is subject to decalcification is not acceptable
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 900
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 255

Exclusion Criteria

Inability to comply with study and fup
History of malabsorpt. syndr. or condit. that would interfere with enteral absorpt. or results in the inability or unwillingness to swallow pills
Severe infec. Within 4w. prior to study treat. or treat. With antibiotics within 2w. prior to study treat. Pts receiving prophylactic antibiotics are eligible
Known HIV infect. and his. of liver disease consistent with ChildPugh ClassB or C
Curr. treat. with antiviral for HB
Major surgical proc., open biopsy or traumatic injury within 28d. prior to D1C1 or anticipat. of need for a maj. surgical proced. during the study
NYHA ClassII,III,IV heart failure;left ventricular eject. fract.<50% or active ventricular arrhythmia req. med.
Curr. unstable angina or history of myocardial infarct. within 6m. prior to D1C1
Congenital long QT syndr. or screening QT interval corrected with Fridericia's formula>480ms
Curr. treat. with med. used at doses known to cause clin. relevant prol. of QT/QTc interval
History or pres. of a clinically significant abnormal ECG
Req. for chronic corticosteroid therapy of >10mg of prednisone per d. or an equivalent dose of other antiinflamm. corticosteroids or immunosuppr. agents for a chronic disease
Treat. with approved or invest. cancer therapy within 14d. prior to D1C1
Any other disease, metabolic dysfunction, physical exam. or clinical lab. finding with suspicion of a disease or condit.n that contraindicates the use of an investing. drug or that may affect the interpr. of the results or renders the pt at high risk from treat. Complic.
Disease Excl Crit
History of or known presence of brain or spinal cord metastases, during screening or prior radiogr. assessments
Known CNS disease
Known germline BRCA1/2 deleterious mut. unless the pt is not an appropr. candidate for a PARP-inhib.
Prev. systemic therapy for inoperable locally advanced or metastatic triplenegative adenocarcinoma of the breast
Unresol. tox. from prior therapy,except alopecia and Gr.1 peripheral neuropathy
Pt who have received palliative radioth. to peripheral sites for pain control and whose last treat. was compl.14d. prior to D1 of C1 may be enrolled in the study if they have recovered from acute, reversible effects
Uncontroll.pleural or pericard. effusion,or ascites,tumor related pain or symptomatic hypercalcemia req. use of bisphosphon.
Malign. other than breast can. within 5y. prior to D1C1,except for treated carcinoma in situ of the cervix,nonmelanoma skin carcinoma,St.I uterine can.
Known hypersensitivity or contraindicate. to any component of the study treat.
Gr.>= 2 peripheral neuropathy
Ipat Excl Crit
History of Type I or II diabetes mellitus requiring insulin or active inflamm. bowel disease or active bowel inflamm.
Gr.>=2 uncontroll. or untreat. hypercholesterolemia or hypertriglyceridemia
Pneumonitis,interstitial lung disease,idiopathic pulmonary or cystic fibrosis,aspergillosis,active tuberculosis or history of opportunistic infections
Treat. with strong CYP3A inhibitors or inducers within 2w. or 5 drugeliminat. halflives prior to initiat. of study drug
Prior treat. with an Akt Inhib.
Atezo Excl Crit
Active or his. of autoimmune disease or immune deficiency
His. of idiopathic pulmonary fibrosis,organizing pneumonia,drug induced or idiopathic pneumonitis,or evidence of active pneumonitis on screen. chest CTscan
Prior allog. stem cell or solid organ transplantat.
Treat. with a live, attenuated vaccine within 4w. prior to initiat. of study treat.,or anticipat

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified