AzTrials
AzTrials

Solid TumorPhase 1NCT04316169

Hydroxychloroquine, Abemaciclib and Endocrine Therapy in Hormone Receptor Positive (HR+)/Her 2 Negative Breast Cancer

A Phase 1 study testing Abemaciclib, Hydroxychloroquine 200 mg and Faslodex in people with Solid Tumor and Advanced Breast Cancer, run by Medical College of Wisconsin at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
Search all trials

Trial summary

The hypothesis is that abemaciclib synergizes with autophagy inhibitor hydroxychloroquine (HCQ/ Plaquenil), inducing apoptosis leading to tumor regression. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Solid Tumor, Advanced Breast Cancer
What is being tested?
Abemaciclib, Hydroxychloroquine 200 mg and Faslodex
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteUnited States
Study dates
21 Oct 2021to Jan 2028
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients with advanced or metastatic cancers who are refractory to standard therapy, relapsed after standard therapy, or who have no standard therapy available that improves progression-free or overall survival by at least three months.
  • Intact G1/S checkpoint in tumor tissue defined by positive-Rb staining and negative-low-molecule weight isoforms of cyclin E (LMWE) with staining done on formalin-fixed paraffin embedded slides from archival tissue or cell blocks.
  • Demonstrate measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST)1.1 criterion.
  • Age ≥ 18 years.
  • Estimated life expectancy of three months.
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
Show all 66Show fewer
  • Patients with asymptomatic central nervous system (CNS) metastases not requiring use of corticosteroids will be allowed.
  • Patients who received chemotherapy must have recovered (Common Terminology Criteria for Adverse Events [CTCAE] Grade ≤1) from the acute effects of chemotherapy except for residual alopecia or Grade 2 peripheral neuropathy prior to randomization. A washout period of at least 21 days is required between the last chemotherapy dose and the first dose of the study drug/s (provided the patient did not receive radiotherapy).
  • Patients who received palliative radiotherapy must have completed and fully recovered from the acute effects of radiotherapy. A washout period of at least 14 days is required between the end of radiotherapy and the first dose of the study drug/s.
  • Patients must be >/= 3 weeks from major surgery. For biologic/targeted agents, patients must be >/= 5 half-lives or >/= 3 weeks from the last dose (whichever comes first).
  • The patient is able to swallow oral medications.
  • Documented ophthalmic exam within the last 12 months demonstrating no evidence of retinopathy. Patients with retinal changes will be considered for enrollment with written clearance from a board-certified ophthalmologist.
  • The patient must sign informed consent prior to registration.
  • The patient has adequate organ function for all of the following criteria, as defined below.
  • Laboratory Value Guidance to Establish Adequate Organ Function
  • Hematologic:
  • Absolute Neutrophil Count (ANC) ≥ 1.5 × 109/L
  • Platelets ≥100 × 109/L
  • Hemoglobin ≥8 g/dL (Patients may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the investigator. Initial treatment must not begin earlier than the day after the erythrocyte transfusion.)
  • Hepatic:
  • Total bilirubin ≤1.5 × upper limit of normal (ULN)
  • Patients with Gilbert's syndrome with a total bilirubin ≤2.0 times ULN and direct bilirubin within normal limits are permitted.
  • Alanine Aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 × ULN
  • Renal:
  • -Creatinine Clearance ≥30 mL/minute
  • Female subjects must meet one of the following:
  • Postmenopausal for at least one year before enrollment, OR
  • Surgically sterile (i.e., undergone a hysterectomy or bilateral oophorectomy), OR
  • If subject is of childbearing potential (defined as not satisfying either of the above two criteria), agrees to practice two acceptable methods of contraception (combination methods require use of two of the following: diaphragm with spermicide, cervical cap with spermicide, contraceptive sponge, male or female condom, hormonal contraceptive) from the time of signing of the informed consent form through 21 days after the last dose of study agent, OR
  • o Agrees to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, postovulation methods] and withdrawal are not acceptable contraception methods.)
  • Male subjects, even if surgically sterilized (i.e., status postvasectomy), must agree to one of the following:
  • Practice effective barrier contraception during the entire study period and through 60 calendar days after the last dose of study agent, OR o Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, post ovulation methods] and withdrawal are not acceptable methods of contraception.)
  • Postmenopausal women with HR+/ Her2- advanced breast cancer with endocrine naïve disease will be enrolled in Cohort A. Endocrine naïve patients are defined as advanced breast cancer patients eligible for first-line aromatase inhibitor in combination with cyclin-dependent kinase (CDK) 4 / 6 inhibitor therapy. Prior endocrine therapy in the neoadjuvant or adjuvant setting is permitted if the patient had a disease-free interval of more than 12 months.
  • Postmenopausal women with HR +/ Her 2 -advanced breast cancer with endocrine pretreated disease will be enrolled in Cohort B. Endocrine pretreated patients are defined as advanced breast cancer patients who progressed while receiving endocrine therapy as first-line therapy or who had prior endocrine therapy in the neoadjuvant or adjuvant setting with a disease-free interval of less than 12 months and who are otherwise eligible to receive a combination of Faslodex® and CDK 4 / 6 inhibitor may be enrolled in Cohort B.
  • Intact G1/S checkpoint in tumor tissue defined by positive-Rb staining and negative-low-molecule weight isoforms of cyclin E (LMWE) with staining done on formalin-fixed paraffin embedded slides from archival tissue or cell blocks.
  • Age ≥ 18 years.
  • Men with advanced breast cancer may be enrolled in Cohort A or B if they meet eligibility criteria as above for post menopausal women.
  • Peri or premenopausal women may be enrolled in Cohort A or B, if they are receiving a gonadotropin-releasing agonist and meet eligibility criteria as above for postmenopausal women.
  • Female subjects must meet one of the following:
  • Postmenopausal for at least one year before enrollment, OR
  • Surgically sterile (i.e., undergone a hysterectomy or bilateral oophorectomy), OR
  • If subject is of childbearing potential (defined as not satisfying either of the above two criteria), agrees to practice two acceptable methods of contraception (combination methods requires use of two of the following: diaphragm with spermicide, cervical cap with spermicide, contraceptive sponge, male or female condom, hormonal contraceptive) from the time of signing of the informed consent form through 21 days after the last dose of study agent. Patients receiving Fulvestrant should use effective contraception for one year after last fulvestrant dose OR o Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, postovulation methods] and withdrawal are not acceptable contraception methods.)
  • Male subjects, even if surgically sterilized (i.e., status postvasectomy), must agree to one of the following:
  • Practice effective barrier contraception during the entire study period and through 60 calendar days after the last dose of study agent, OR
  • Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, postovulation methods] and withdrawal are not acceptable contraception methods.)
  • Patients with asymptomatic CNS metastases not requiring use of corticosteroids will be allowed
  • Estimated life expectancy of at least six months.
  • ECOG performance status ≤2.
  • Demonstrates measurable disease as defined by RECIST 1.1 criteria or non-measurable bone-only disease.
  • Documented ophthalmic exam within the last 12 months demonstrating no evidence of retinopathy. Patients with retinal changes will be considered for enrollment with written clearance from a board-certified ophthalmologist.
  • Must sign informed consent prior to registration.
  • The patient has adequate organ function for all of the following criteria, as defined below.
  • Laboratory Value Guidance to Establish Adequate Organ Function
  • Hematologic
  • ANC ≥ 1.5 × 109/L
  • Platelets ≥100 × 109/L
  • Hemoglobin ≥8 g/dL (Patients may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the investigator. Initial treatment must not begin earlier than the day after the erythrocyte transfusion.)
  • Hepatic
  • Total bilirubin ≤1.5 × ULN
  • Patients with Gilbert's syndrome with a total bilirubin ≤2.0 times ULN and direct bilirubin within normal limits are permitted.
  • ALT and AST ≤3 × ULN
  • Renal
  • Creatinine Clearance ≥30 mL/minute
  • Patients who previously received chemotherapy must have recovered (Common Terminology Criteria for Adverse Events (CTCAE) grade ≤1) from the acute effects of chemotherapy except for residual alopecia or grade 2 peripheral neuropathy prior to randomization. A washout period of at least 21 days is required between last chemotherapy dose and first dose of the study drug/s (provided the patient did not receive radiotherapy).
  • Patients who received palliative radiotherapy must have completed and fully recovered from the acute effects of radiotherapy. A washout period of at least 14 days is required between end of palliative radiotherapy and first dose of the study drug/s.
  • The patient is able to swallow oral medications.

Who cannot join

  • Serious concomitant systemic disorder that would compromise the safety of the patient or compromise the patient's ability to complete the study, as determined by the treating physician or the principal investigator (for example, interstitial lung disease, severe dyspnea at rest, history of major surgical resection involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline grade 2 or higher diarrhea).
  • Second primary malignancy except most in situ carcinomas (e.g., adequately treated non-melanomatous carcinoma of the skin) or other malignancy treated at least five years previously with no evidence of recurrence.
  • Uncontrolled or symptomatic CNS metastases.
  • Known history of glucose-6-phosphate dehydrogenase (G6PD) deficiency.
  • Taking other commercially available medications, which may theoretically either stimulate or inhibit autophagy; these include calcitriol and chloroquine.
  • Taking medications which may lead to interactions with HCQ, including penicillamine, telbivudine, botulinum toxin, digoxin and propafenone.
Show all 33Show fewer
  • Must not be taking HCQ at baseline.
  • Females who are pregnant or lactating.
  • Uncontrolled infections including and not limited to active bacterial infection (requiring intravenous [IV] antibiotics at time of initiating study treatment), fungal infection, human immunodeficiency virus infection with cluster of differentiation 4 (CD4) counts less than 350 and/or AIDS defining opportunistic illnesses known active hepatitis B [for example, hepatitis B surface antigen positive], patients with hepatitis C antibody with detectable hepatitis C viral load.. Screening tests are NOT required for this criterion.
  • The patient has a marked baseline prolongation of QT/QTc interval >470 millisecond using Fridericia's QT correction formula or a personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), sudden cardiac arrest, family history of Long QT syndrome.
  • Patients with symptomatic heart failure, uncontrolled arrhythmia, hypokalemia that does not respond to supplementation
  • Patient receiving treatment with strong and moderate Cytochrome P450, family 3, subfamily A (CYP3A) inducers within seven days prior to the first dose of study drugs.
  • Patient receiving treatment with tamoxifen within seven days prior to the first dose of study drugs.
  • Patient receiving treatment with live vaccines within 30 days prior to the first dose of study drugs.
  • Patients receiving medications including herbal supplements which may prolong the QT interval.
  • Eligibility criteria- Part 2 (Enrollment criteria for the dose-expansion phase)
  • Presence of visceral crisis, lymphangitic spread, leptomeningeal carcinomatosis or inflammatory breast cancer.
  • Prior therapy with a CDK 4/6 inhibitor.
  • Serious concomitant systemic disorder that would compromise the safety of the patient or compromise the patient's ability to complete the study, as determined by the treating physician or the principal investigator (for example, interstitial lung disease, severe dyspnea at rest, history of major surgical resection involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline grade 2 or higher diarrhea).
  • Second primary malignancy except most in situ carcinoma (e.g., adequately treated non-melanomatous carcinoma of the skin) or other malignancy treated at least five years previously with no evidence of recurrence.
  • Uncontrolled or symptomatic CNS metastases.
  • Known history of G6PD deficiency.
  • Taking other commercially available medications which may theoretically either stimulate or inhibit autophagy; these include calcitriol and chloroquine.
  • Taking medications which may lead to interactions with HCQ, including penicillamine, telbivudine, botulinum toxin, digoxin, and propafenone.
  • Must not be taking HCQ at baseline.
  • Females who are pregnant or lactating.
  • The patient has active bacterial infection (requiring intravenous [IV] antibiotics at time of initiating study treatment), fungal infection, or detectable viral infection (such as known human immunodeficiency virus positivity or with known active hepatitis B or C [for example, hepatitis B surface antigen positive]). No screening tests is required for this criterion.
  • The patient has a marked baseline prolongation of QT/QTc interval >470 millisecond using Fridericia's QT correction formula or a personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest ,family history of Long QT syndrome.
  • Patients with symptomatic heart failure, uncontrolled arrhythmia, hypokalemia that does not respond to supplementation
  • Patient receiving treatment with strong and moderate CYP3A inducers within seven days prior to the first dose of study drugs.
  • Patient receiving treatment with tamoxifen within seven days prior to the first dose of study drugs.
  • Patient receiving treatment with live vaccines within 30 days prior to the first dose of study drugs.
  • Patients receiving medications, including herbal supplements, which may prolong the QT interval.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Froedtert Hospital and the Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

Other trials in United States

About this study

Official title: Hydroxychloroquine (HCQ) in Combination With Abemaciclib and Endocrine Therapy in HR+/Her 2- Advanced Breast Cancer After a Lead in Dose Escalation Cohort of HCQ and Abemaciclib in Advanced Solid Tumors

The hypothesis is that abemaciclib synergizes with autophagy inhibitor hydroxychloroquine (HCQ/ Plaquenil), inducing apoptosis leading to tumor regression.

Read the detailed description

Part 1: 3+3 dose escalation of HCQ combined with abemaciclib in advanced solid tumors.

Part 2: HCQ at top-dose level from part one is combined with abemaciclib and endocrine therapy in HR+/Her 2- advanced breast cancer (ABC) and divided into two cohorts based on prior exposure to endocrine therapy.

Primary Objective

  1. Dose-escalation cohort: To determine safety and tolerability of HCQ combined with abemaciclib.
  2. Dose-expansion cohort: To determine safety and tolerability of HCQ combined with abemaciclib and endocrine therapy in HR+/Her2- ABC.

Secondary Objectives

  1. To assess the clinical efficacy of HCQ in combination with abemaciclib and hormone blockade in the dose- expansion cohort of advanced ER- positive breast cancer participants.
  2. To assess the clinical efficacy of HCQ in combination with abemaciclib in the dose- escalation cohort
Being tested
Abemaciclib, Hydroxychloroquine 200 mg, Faslodex, Anastrazole, Letrozole

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AbemaciclibDrug

    Also called Verzenio

    150 mg b.i.d

  • Hydroxychloroquine 200 mgDrug

    Also called Plaquenil

    Dose level: 200 mg b.i.d.

  • FaslodexDrug

    Also called Fulvestrant

    Cohort B will receive Faslodex.

  • AnastrazoleDrug

    Also called Arimidex

    Cohort A will receive anastrazole or letrozole.

  • LetrozoleDrug

    Also called Femara

    Cohort A will receive anastrazole or letrozole.

  • Hydroxychloroquine 400 mgDrug

    Also called Plaquenil

    Dose level: 400 mg. b.i.d.

  • Hydroxychloroquine 600 mgDrug

    Also called Plaquenil

    Dose level: 600 mg b.i.d.

Study groups in NCT04316169
Study groupRoleWhat they receive
Abemaciclib and HCQ 200 mg b.i.d.ExperimentalHCQ will have a dose escalation of a 3 + 3 design.
Receives: Drug: Abemaciclib; Drug: Hydroxychloroquine 200 mg
Abemaciclib and HCQ 400 mg b.i.d.ExperimentalHCQ will have a dose escalation of a 3 + 3 design.
Receives: Drug: Abemaciclib; Drug: Hydroxychloroquine 400 mg
Abemaciclib and HCQ 600 mg b.i.d.ExperimentalHCQ will have a dose escalation of a 3 + 3 design.
Receives: Drug: Abemaciclib; Drug: Hydroxychloroquine 600 mg
Abemaciclib + HCQ (Optimal Dose) + endocrine therapyExperimentalThis group will be divided into two cohorts: 1. eligible participants who are endocrine therapy naive. 2. eligible participants who had one prior line of endocrine therapy.
Receives: Drug: Abemaciclib; Drug: Hydroxychloroquine 200 mg; Drug: Faslodex; Drug: Anastrazole; Drug: Letrozole; Drug: Hydroxychloroquine 400 mg; Drug: Hydroxychloroquine 600 mg

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dose-limiting toxicities during dose-escalation phase.

    The number of participants with dose-limiting toxicities during the dose-escalation phase (HCQ in combination with abemaciclib).

    Measured: 28 days for each cohort

  2. Dose-limiting toxicities in dose-expansion phase.

    The number of participants with dose-limiting toxicities during the dose-expansion phase (maximum-tolerated dose of HCQ and abemaciclib in combination with endocrine therapy.

    Measured: 28 days for each cohort

Secondary outcomes (2)

  1. Progression-free survival.

    This measure is the number of months participants remain free from evidence of disease. Participants will undergo imaging every eight weeks and results will be reported annually.

    Measured: 1 Year

  2. Overall response rate.

    The number of participants who have a partial or complete response based on tumor measurement by CT or MRI using RECIST 1.1. Participants will be imaged every eight weeks and reported annually.

    Measured: 1 Year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Mar 2020
  2. Study start21 Oct 2021
  3. Primary completionJan 2027 (estimated)
  4. Study completionJan 2028 (estimated)

Why it stopped: Funding and PI leaving institution

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04316169
Sponsor's protocol ID
PRO00035701
Status last verified
Dec 2022
First submitted
18 Mar 2020
Last updated
23 Dec 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Abemaciclib, Hydroxychloroquine 200 mg and Faslodex in people with Solid Tumor and Advanced Breast Cancer, run by Medical College of Wisconsin at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 66 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 23 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose-limiting toxicities during dose-escalation phase. (time frame: 28 days for each cohort). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04316169.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Dec 2022.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in