Clinical Trials /

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

NCT03959891

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: AKT Inhibitor, Ipatasertib, With Endocrine and CDK 4/6 Inhibitor for Patients With Metastatic Breast Cancer (TAKTIC)
  • Official Title: Clinical Trial to Evaluate Safety and Anti-tumor Activity of AKT Inhibitor, Ipatasertib,With Endocrine Therapy With/Without CDK 4/6 Inhibitor for Patients With Metastatic Hormone Receptor Positive Breast Cancer (TAKTIC)

Clinical Trial IDs

  • ORG STUDY ID: 19-086
  • NCT ID: NCT03959891

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
IpatasertibGDC-0068Fulvestrant + Ipatasertib
FulvestrantFalsodexFulvestrant + Ipatasertib
Aromatase InhibitorLetrozoleAromatase Inhibitor + Ipatasertib
PalbociclibIbranceFulvestrant + Ipatasertib +Palbociclib

Purpose

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.

Detailed 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.
    

Trial Arms

NameTypeDescriptionInterventions
Fulvestrant + IpatasertibExperimentalIpatasertib 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.
  • Ipatasertib
  • Fulvestrant
Aromatase Inhibitor + IpatasertibExperimentalIpatasertib will be administered orally on a daily basis Aromatase inhibitors will be administered orally on a daily basis
  • Ipatasertib
  • Aromatase Inhibitor
Fulvestrant + Ipatasertib +PalbociclibExperimentalIpatasertib 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
  • Ipatasertib
  • Fulvestrant
  • Palbociclib

Eligibility Criteria

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of Treatment-Emergent Adverse Events
Time Frame:2 years
Safety Issue:
Description:grade 1-5 (CTCAE)

Secondary Outcome Measures

Measure:Progression Free Survival
Time Frame:2 years
Safety Issue:
Description:Kaplan-Meier Analysis
Measure:Overall Response Rate
Time Frame:2 years
Safety Issue:
Description:RECIST criteria
Measure:Complete Response
Time Frame:2 Years
Safety Issue:
Description:RECIST criteria
Measure:Partial Response
Time Frame:2 years
Safety Issue:
Description:RECIST criteria
Measure:Overall Survival
Time Frame:2 Years
Safety Issue:
Description:Kaplan-Meier Analysis

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Massachusetts General Hospital

Trial Keywords

  • Breast Cancer

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