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

NCT03959891 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 19-086
• Study Type: interventional
• Target: 77
• Locations: 1 country
• Sites: 1

Brief Summary

This study is exploring the safety/tolerabtility and preliminary efficacy of the combination of Ipatasertib with Aromatase inhibitor or Fulvestrant for patients with metastatic HR+ breast cancer.

Conditions

Breast Cancer

Keywords

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Incidence of Treatment-Emergent Adverse Events

  grade 1-5 (CTCAE)

  2 years

Secondary Outcomes (5)

• Progression Free Survival

  2 years

• Overall Response Rate

  2 years

• Complete Response

  2 Years

• Partial Response

  2 years

• Overall Survival

  2 Years

Study Arms (3)

Fulvestrant + Ipatasertib

EXPERIMENTAL

* Ipatasertib will be administered orally on a daily basis * Fulvestrant would be administered as intra-muscular injection twice a month for the first cycle, and then monthly for all other cycles.

Drug: Ipatasertib; Drug: Fulvestrant

Aromatase Inhibitor + Ipatasertib

EXPERIMENTAL

* Ipatasertib will be administered orally on a daily basis * Aromatase inhibitors will be administered orally on a daily basis

Drug: Ipatasertib; Drug: Aromatase Inhibitor

Fulvestrant + Ipatasertib +Palbociclib

EXPERIMENTAL

* Ipatasertib will be administered orally on a 3 week on and 1 week off schedule * Fulvestrant would be administered as intra-muscular injection twice a month for the first cycle, and then monthly for all other cycles. * Palbociclib will be administered orally on a 3 week on and 1 week off schedule

Drug: Ipatasertib; Drug: Fulvestrant; Drug: Palbociclib

Interventions

Ipatasertib DRUG

Ipatasertib is a type of inhibitor that is believed to work by inhibiting Akt.

Also known as: GDC-0068

Aromatase Inhibitor + Ipatasertib; Fulvestrant + Ipatasertib; Fulvestrant + Ipatasertib +Palbociclib

Fulvestrant DRUG

Hormone therapies work by stopping the production of a certain hormone, blocking hormone receptors, or substituting chemically similar agents for the active hormone, which cannot be used by the tumor cell.

Also known as: Falsodex

Fulvestrant + Ipatasertib; Fulvestrant + Ipatasertib +Palbociclib

Aromatase Inhibitor DRUG

Letrozole is an aromatase inhibitor. This means it blocks the enzyme aromatase (found in the body's muscle, skin, breast and fat), which is used to convert androgens (hormones produced by the adrenal glands) into estrogen. In the absence of estrogen, tumors dependent on this hormone for growth will shrink.

Also known as: Letrozole

Aromatase Inhibitor + Ipatasertib

Palbociclib DRUG

Palbociclib (Ibrance®) is a drug that can be used along with an aromatase inhibitor to treat women with advanced hormone receptor-positive breast cancer. Palbociclib is a reversible small molecule cyclin-dependent kinase (CDK) inhibitor. The drug blocks proteins in the cell called cyclin-dependent kinase (CDK) 4 and CDK 6. In hormone positive breast cancer cells, blocking these proteins helps stop the cells from dividing to make new cells. It helps prevent the cells from moving from G1 to S cell cycle phase in the division process. This slows cancer growth.

Also known as: Ibrance

Fulvestrant + Ipatasertib +Palbociclib

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Genentech, Inc.: collaborator

Study Sites (1)

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

ipatasertib; Fulvestrant; Aromatase Inhibitors; Letrozole; palbociclib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Steroid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Estrogen Antagonists; Hormone Antagonists; Physiological Effects of Drugs; Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Seth Wander, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 15, 2019
• First Posted: May 22, 2019
• Study Start: May 30, 2019
• Primary Completion: December 25, 2022
• Study Completion (Estimated): July 1, 2026
• Last Updated: September 29, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: BCH - Contact the Technology \& Innovation Development Office at www.childrensinnovations.org or email TIDO@childrens.harvard.edu BIDMC - Contact the Beth Israel Deaconess Medical Center Technology Ventures Office at tvo@bidmc.harvard.edu BWH - Contact the Partners Innovations team at http://www.partners.org/innovation DFCI - Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu MGH - Contact the Partners Innovations team at http://www.partners.org/innovation

Locations

US (1)