AKT Inhibitor Ipatasertib With Endocrine and CDK 4/6 Inhibitor for Patients With Metastatic Breast Cancer (TAKTIC)

  • STATUS
    Recruiting
  • End date
    Jun 30, 2024
  • participants needed
    60
  • sponsor
    Massachusetts General Hospital
Updated on 25 January 2021
estrogen
measurable disease
AKT
endocrine therapy
metastasis
hormone therapy
HER2
cancer treatment
gonadotropin releasing hormone
tamoxifen
estradiol
fulvestrant
stage iv breast cancer
erbb2
aromatase inhibitor
palbociclib
letrozole
immunostimulant
mammogram

Summary

This research is looking to find out if the combination of Ipatasertib with Aromatase inhibitor or Fulvestrant can be an effective treatment for breast cancer.

Description

This research study is a Phase I clinical trial, which tests the safety of an investigational drug and also tries to define the appropriate dose of the investigational drug to use for further studies. "Investigational" means that the drug is being studied.

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

The FDA has approved fulvestrant, the aromatase inhibitors, and palbociclib as treatment options for this disease.

This research study will evaluate the safety and tolerability of ipatasertib in combination with an aromatase inhibitor or fulvestrant with or without palbociclib.

Resistance to standard of care treatment for people with your type of cancer is common. Stopping (inhibiting) an enzyme called Akt in the cancer cells may overcome resistance to the standard of care treatment. Ipatasertib is a type of inhibitor that is believed to work by inhibiting Akt. Through the different combinations of ipatasertib and the standard of care drugs, the chance of cancer cells becoming resistant to the standard of care drugs may decrease, causing the cancer cells to stop growing and spreading.

Details
Condition Breast Cancer, Breast Cancer Diagnosis, breast carcinoma, cancer, breast
Treatment fulvestrant, Palbociclib, Ipatasertib, Aromatase Inhibitor
Clinical Study IdentifierNCT03959891
SponsorMassachusetts General Hospital
Last Modified on25 January 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Adult women ( 18 years of age) with biopsy proven HR+/HER2 negative breast cancer; HR+ defined as 1% positivity for ER, and/or PR (1%), as per local assessment. HER2 as per standard CAP guidelines (local assessment)
Postmenopausal women with locally advanced or metastatic BC. Patients must be postmenopausal women as defined by one of the following
Women >60 years OR
Women 60 years, and any one of following
LH and FSH level in the postmenopausal range according to institutional standards
s/p post bilateral surgical oophorectomy
Premenopausal/perimenopausal women on gonadotropin-releasing hormone agonist (to be continued during study) and estradiol level in the postmenopausal range according to institutional standards
Disease progression on at least one prior therapy for metastatic disease, including endocrine therapy with/without CDK 4/6 inhibitor (palbociclib or ribociclib or abemaciclib). Disease recurrence during/within 12 month of (neo)adjuvant endocrine therapy (with/without CDK 4/6 inhibitor) will count as one prior therapy for this definition
ECOG Performance Status 0 - 2
Left ventricular ejection fraction (LVEF) 50%
Evaluable or measurable disease: at least one lesion that can be accurately measured in at least one dimension 20 mm with conventional imaging techniques or 10 mm with spiral CT or MRI. Bone lesions in the absence of measurable disease as defined above is also acceptable
Discontinuation of prior breast cancer therapies, including endocrine therapy, for 14 days (non-myelosuppressive) or 21 days (myelosuppressive). Wash-out for Fulvestrant and tamoxifen will be 28 days
Prior mTOR inhibitor and/or PI3K inhibitor allowed (all arms)
Prior aromatase inhibitor is allowed (all arms)
Adequate bone marrow function: ANC 1000/mm3, hemoglobin 9 g/dl, and platelets 100,000/mm3
Adequate hepatic function: Total bilirubin < 1.5mg/dL, AST and ALT < 3X Institutional ULN (or 5 X Institutional ULN in presence of hepatic mets)
Adequate renal function: Calculated creatinine clearance 30 mL/min
Fasting blood glucose <140 mg/dL, and hemoglobin A1c <7\
Signed informed consent and agree to comply with study procedures

Exclusion Criteria

Participants with progressive CNS metastatic disease. Patients with stable CNS metastasis would be eligible, provided mets radiologically stable for atleast one month, and patient is not actively taking steroids
Participants who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
Prior use of AKT inhibitor (any setting)
Treatment with strong CYP3A inhibitors or strong CYP3A inducers within 14 days or 5 drug-elimination half-lives, whichever is longer, prior to initiation of study treatment. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated list such as <http://medicine.iupui.edu/clinpharm/ddis/table.aspx>; medical reference texts such as the Physicians' Desk Reference may also provide this information. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs (e.g., inflammatory bowel disease, ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality including any of the following
History of angina pectoris, symptomatic pericarditis, coronary artery bypass graft (CABG) or myocardial infarction within 6 months prior to study entry
Documented cardiomyopathy
History of cardiac failure, significant/symptomatic bradycardia, Long QT syndrome, family history of idiopathic sudden death or congenital long QT syndrome or any of the following
Known risk to prolong the QT interval or induce Torsade's de Pointes
Uncorrected hypomagnesemia or hypokalemia
Systolic Blood Pressure (SBP) >160 mmHg or <90 mmHg
Bradycardia (heart rate <50 at rest), by ECG or pulse
On screening, inability to determine the QTcF interval on the ECG (i.e.: unreadable or not interpretable) or QTcF >450 screening ECG (based on a mean of 3 ECGs)
HIV-positive participants on combination antiretroviral therapy are ineligible. These participants are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in participants receiving combination antiretroviral therapy when indicated
History of Type I or Type II diabetes mellitus requiring insulin. Patients who are on a stable dose of oral diabetes medication 2 weeks prior to initiation of study treatment are eligible for enrollment. Patients must meet the laboratory eligibility criteria for fasting blood glucose and hemoglobin A1c as outlined in the inclusion criteria
Pregnant women are excluded from this study because the safety of study medications is not established in pregnant women
Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception throughout the study and for 8 weeks after study drug discontinuation. Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago. In the case of bilateral oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential. Highly effective contraception methods include
Total abstinence when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception
Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy, or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment
Use of oral, injected or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS), or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception
In case of use of oral contraception, women should have been stable on the same pill for a minimum of 3 months before taking study treatment. Note: While oral contraceptives are allowed, they should be used in conjunction with a barrier method of contraception due to unknown effect of drug-drug interaction
For Arm A only: patients who have received prior fulvestrant
For Arm C only: h/o of intolerable toxicity to CDK 4/6 inhibitor resulting in treatment discontinuation due to toxicity
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