Ipatasertib + Atezolizumab to Prevent Recurrence in TNBC

STATUS

Recruiting
participants needed

40
sponsor

Dana-Farber Cancer Institute

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Updated on 19 February 2024

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cancer

probe

hysterectomy

blood transfusion

breast cancer

platelet count

hba1c

white blood cell count

atezolizumab

gilbert's syndrome

treatment regimen

immune checkpoint inhibitor

anticoagulants

bisphosphonate

ipatasertib

granulocyte colony stimulating factor

sentinel node

mastectomy

lumpectomy

invasive breast cancer

immunohistochemistry

axillary lymph node dissection

breast surgery

sentinel lymph node biopsy

immunomodulators

serum bilirubin

lymphadenectomy

menstrual period

g-csf

colony stimulating factor

adjuvant therapy

aptt

breast irradiation

serum bilirubin level

immunostimulant

cfdna

absolute lymphocyte count

adjuvant

HER2

triple negative breast neoplasms

Summary

The purpose of this study is to determine if a combination of two drugs ipatasertib and atezolizumab works as a treatment for residual cancer in the breast or lymph nodes and have circulating tumor DNA in the blood.

This research study involves the following investigational drugs:

Ipatasertib
Atezolizumab

Description

This is an open label single-arm phase II study to evaluate the combination therapy of the AKT inhibitor, ipatasertib, and the anti-PD-L1 antibody, atezolizumab, in patients with triple negative breast cancer.

The research study procedures include screening for eligibility and study treatment including laboratory evaluations, stool collection and follow up visits.

This research study involves the following investigational drugs:

Ipatasertib
Atezolizumab

Participants will receive study treatment for 24 weeks and will be followed for every 6 months for 3 years.

It is expected that about 40 people will take part in this research study.

This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug to learn whether the drug or drug combination works in treating a specific disease. "Investigational" means that the drug combination is being studied.

The U.S. Food and Drug Administration (FDA) has not approved atezolizumab (Tecentriq) for residual triple negative breast cancer but it has been approved for advanced triple negative breast cancer and other cancers. Atezolizumab is a protein that affects your immune system by blocking the PD-L1 pathway. The PD-L1 pathway controls your body's natural immune response, but for some types of cancer the immune system does not work as it should and is prevented from attacking tumors. Atezolizumab works by blocking the PD-L1 pathway, which may help your immune system identify and catch tumor cells.

The U.S. Food and Drug Administration (FDA) has not approved ipatasertib as a treatment for any disease.

Ipatasertib is a drug that inhibits (stops) an enzyme called Akt in cancer cells. It is thought that inhibiting Akt may make cancer cells more sensitive to treatment, especially in combination with a drug that activates the immune system, like atezolizumab.

Details

Condition	Minimal Residual Disease, Breast Cancer, Breast Cancer, Breast Cancer - HER2 Positive, Chronic Shoulder Pain, Circulating Tumor DNA
Age	18-100 years
Treatment	Atezolizumab, Ipatasertib
Clinical Study Identifier	NCT04434040
Sponsor	Dana-Farber Cancer Institute
Last Modified on	19 February 2024

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Eligibility		Yes	No	Not Sure
Inclusion Criteria
	Pathologically confirmed residual invasive breast cancer, in the breast and/or lymph node(s), following neoadjuvant chemotherapy. In the absence of residual invasive disease in the breast, lymph node must contain at least 2mm of invasive disease
	HER2 negative by local pathology assessed according to current ASCO/CAP guidelines
	In situ hybridization non-amplified (ratio of HER2 to CEP17 < 2.0 or single probe average HER2 gene copy number < 4 signals/cell), OR
	Immunohistochemistry (IHC) 0 or IHC 1+
	NOTE: If more than one test result is available and not all results meet the inclusion criterion definition, all results should be discussed with the Principal Investigator to establish eligibility
	ER and PR negative defined as < 1% of cells expressing hormonal receptors via IHC analysis by local laboratory assessment
	Patients must have received neoadjuvant chemotherapy prior to breast surgery. Investigational agents as part of the neoadjuvant regimen are allowed, with the exception of PI3K/Akt/mTor inhibitors and/or immune checkpoint inhibitors
	Patients must be within 12 months of last therapy (definitive breast surgery, radiation and/or all intended adjuvant therapy). Definitive breast surgery includes lumpectomy or mastectomy with pathologically clear margins (i.e. no ink on tumor). For patients undergoing lumpectomy, this must be followed by whole breast irradiation. Definitive surgery also includes axillary surgery, either sentinel lymph node biopsy or axillary lymph node dissection at the discretion of the attending surgeon
	Evidence of circulating tumor cfDNA in blood sample collected after completion of all local and systemic neoadjuvant and adjuvant therapy (preoperative and postoperative chemotherapy, surgery and radiation), confirmed by central testing. Detection of any tumor specific mutations (TSMs) within the sample will be considered positive for purposes of study eligibility
	Concurrent receipt of bone modifying agents (bisphosphonates or rank-ligand inhibitors)is allowed
	ECOG Performance Status of 0 or 1
	Men and women, age 18 years
	Adequate hematologic and organ function defined by the following
	ANC 1.5 109/L (1500/L) without granulocyte colony-stimulating factor support
	WBC count 2.5 109/L (2500/L)
	Absolute Lymphocyte count 0.5 109/L (500/L)
	Platelet count 100 109/L (100,000/L)
	Hemoglobin 90 g/L (9.0 g/dL), with or without transfusion
	AST, ALT, and alkaline phosphatase (ALP) 2.5 institutional upper limit of normal (ULN)
	Serum bilirubin 1.5 institutional ULN with the following exception
	Patients with known Gilbert syndrome: serum bilirubin level 3 institutional ULN
	Serum creatinine < 1.5 x institutional ULN
	Serum albumin 25 g/L (2.5 g/dL)
	Fasting glucose < 150 mg/dL and hemoglobin (HBA1c) < 7.5%
	For patients not receiving therapeutic anticoagulation: INR or aPTT 1.5 institutional ULN
	For patients receiving therapeutic anticoagulation: stable anticoagulant regimen
	Women of childbearing potential (pre-menopausal) must have a negative serum or urine pregnancy test within 7 days prior to start of therapy. A woman is defined as premenopausal if she is less than 12 months from last menstrual period with no identified cause other than menopause (medication induced amenorrhea is not acceptable). Pregnancy test is not required in women who are surgically sterile via bilateral salpingooophorectomy or hysterectomy
	Women of childbearing potential and men must agree to use adequate contraception for the duration of protocol treatment and for 28 days after last dose of ipatasertib and 5 months after stopping atezolizumab. Hormonal contraceptives are not acceptable (see section 5.6)
	Ability to understand and the willingness to sign a written informed consent document
	Patients must be willing to provide archival tissue for research purposes
Exclusion Criteria
	Clinical evidence of metastatic disease
	Residual DCIS or LCIS alone without invasive cancer OR pT0N0i and pT0N1mic residual disease
	Prior treatment with an immune checkpoint inhibitor is permitted in the neoadjuvant setting and prohibited in the adjuvant setting
	Concurrent enrollment on another investigational therapy trial
	Prior treatment-related toxicity must be resolved to Grade 1 with the exception of alopecia and peripheral neuropathy, prior to study enrollment
	Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the study
	Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment Patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study
	Intercurrent illness including, but not limited to: ongoing or active infection requiring systemic therapy, active tuberculosis, serious liver disease such as cirrhosis, active bleeding diathesis, uncontrolled Type I or Type II diabetes mellitus, Grade 2 uncontrolled or untreated hypercholesterolemia, Hypertriglyceridemia or hypercalcemia
	Cardiovascular disease including: congestive heart failure of New York Heart Association Class III or IV, myocardial infarction (<6 months prior to enrollment) unstable angina pectoris, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease, in the opinion of the investigator
	History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted
	Active (acute or chronic) autoimmune disease of any type except hypothyroidism on a thyroid-replacement hormone,or celiac disease, or well-controlled psoriasis, eczema, lichen simplex chronicus or vitiligo
	Impairment of gastrointestinal function or active gastrointestinal disease that may significantly alter the absorption of the study agents (e.g., ulcerative disease, uncontrolled nausea(> grade 2), vomiting (> grade 2), diarrhea (> grade 2), malabsorption syndrome or small bowel resection)
	Congenital long QT syndrome or screening QT interval corrected through use of Fridericia's formula >480 ms
	Participants known to be positive for the human immunodeficiency virus (HIV), Hepatitis B antigen (HepBsAg), or Hepatitis C virus (HCV) RNA are ineligible
	History of prior invasive breast cancer in either breast
	Participants with history of prior malignancy other than breast cancer are eligible if they have been disease-free for at least 5 years prior to enrollment with the exception of patients with thyroid cancer that has been definitively treated without spread to regional lymph nodes
	Treatment with strong CYP3A4 inducers within 4 weeks or 5 drug-elimination half-lives, whichever is longer, prior to initiation of study drug
	Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine while on protocol treatment
	Known allergy or hypersensitivity to any of the study drugs or any of their excipients, including chimeric or humanized antibodies or fusion proteins and Chinese hamster ovary cell products or recombinant human antibodies
	Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and antitumor necrosis factor alpha agents) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during the course of the study, with the following exceptions
	Patients who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible. o Patients who received mineralocorticoids (e.g., fludrocortisone), corticosteroids for chronic obstructive pulmonary disease or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the study
	Pregnant women are excluded from this study because the effects of ipatasertib and atezolizumab on a developing fetus are unknown. Breastfeeding should be discontinued prior to entry onto the study

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white blood cell count

atezolizumab

gilbert's syndrome

treatment regimen

immune checkpoint inhibitor

anticoagulants

bisphosphonate

ipatasertib

granulocyte colony stimulating factor

sentinel node

mastectomy

lumpectomy

invasive breast cancer

immunohistochemistry

axillary lymph node dissection

breast surgery

sentinel lymph node biopsy

colony stimulating factor

adjuvant therapy

aptt

breast irradiation

serum bilirubin level

immunostimulant

cfdna

absolute lymphocyte count

adjuvant

HER2

triple negative breast neoplasms

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Ipatasertib + Atezolizumab to Prevent Recurrence in TNBC