Metastatic Breast CancerPhase 1NCT04872608
A Study of Letrozole, Palbociclib, and Onapristone ER in People With Metastatic Breast Cancer
A Phase 1 study testing Letrozole, Palbociclib and Onapristone ER in people with Metastatic Breast Cancer and Unresectable Breast Cancer, run by Memorial Sloan Kettering Cancer Center at 1 site in United States.
Trial summary
The researchers are doing this study to find out whether the study drug onapristone ER, combined with the standard treatment for your cancer (letrozole and palbociclib), is a safe treatment for people who have metastatic or unresectable ER+/PR+/HER2- breast cancer. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Metastatic Breast Cancer, Unresectable Breast Cancer
- What is being tested?
- Letrozole, Palbociclib and Onapristone ER
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 9 Sep 2021to 25 Apr 2023
- 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
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed ER+, PR+, HER2- metastatic or unresectable breast cancer
- PR positivity is defined as ≥1% expression by immunohistochemistry (IHC) on fresh or archival tumor tissue
- Tissue samples obtained, stained, and interpreted outside of MSKCC will be accepted
- Those patients who do not have adequate/accessible archival tissue available and for whom biopsy is not a significant risk procedure may be required to consent to pretreatment biopsy
- Completed at least 6 months (+/- 4 weeks) of first-line letrozole/palbociclib without radiological progression or unresolved toxicity
- °Patients who underwent dose reduction of palbociclib to 100mg daily or 75mg daily will be eligible if:
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- The dose reduction was implemented ≥4 weeks prior to enrollment
- Patients have demonstrated resolution of all acute toxic effects of prior therapy to NCI CTCAE (Version 5.0) Grade ≤ 1
- ctDNA-positive, defined as:
- °Presence of a tumor-derived somatic mutation in the peripheral blood using the MSK-ACCESS assay after 6 months of letrozole/palbociclib (+/- 4 weeks); at least one mutation should have avariant allele fraction of ≥ 0.5%
- Completed MSK IMPACT testing from primary or metastatic tissue
- Radiologically evaluable or measurable disease per RECIST Version 1.1
- Age ≥ 18 years
- Pre-menopausal patients are eligible as long as they are on LHRH agonist for at least four weeks prior to starting trial therapy and commit to continue LHRH agonist for as long as patient is receiving trial therapy or medical contraindications arise.
- Eastern Cooperative Oncology Group Performance Status (ECOG) of 1 or Karnofsky Performance Status (KPS) of ≥ 70%
- Women of child-bearing potential:
- Must have a negative pregnancy test within 14 days prior to commencement of study treatment
- Agreement to remain abstinent (refrain from heterosexual intercourse) or use nonhormonal contraceptive methods with a failure rate of <1% per year during the treatment period and for 120 days after the last dose and agreement to refrain from donating eggs during this same period
- Note: for women with therapy-induced amenorrhea, baseline measurements of FSH and/or estradiol are needed to ensure menopausal status.
- Adequate hematologic and organ function demonstrated within 14 days prior to initiation of study treatment, defined by the following:
- Absolute neutrophil count ≥ 1.2K/ µL
- Hemoglobin ≥ 9 g/dL
- Platelet count ≥ 100,000/ µL
- Total bilirubin ≤ 1.5 x ULN
- Serum albumin ≥ 2.5 g/dL
- AST and ALT ≤ 2.5 x ULN
- Serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 50 mL/min on the basis of the Cockcroft-Gault glomerular filtration rate estimation
- INR < 1.5 x ULN and aPTT < 1.5 x ULN
- °For patients requiring anticoagulation therapy with warfarin, a stable INR between 2-3 is required. If anticoagulation is required for a prosthetic heart valve, then stable INR between 2.5-3.5 is permitted.
- At least 4 weeks post-op from any major surgical procedure
- Patients with asymptomatic brain metastases which have been treated with surgery or radiation and demonstrate stability for ≥ 3 months will be allowed
- Able to swallow tablets whole, without crushing
Who cannot join
- Radiologic disease progression while on treatment with letrozole and palbociclib in the first line prior to enrollment
- History of another invasive malignancy (other than non-melanoma skin cancer or curatively treated in situ carcinoma) with evidence of disease within the past 3 years
- Any psychological, familial, sociological or geographic condition that would potentially hinder compliance with the study protocol
- Known untreated or symptomatic brain metastasis
- Uncontrolled hypertension (systolic BP ≥ 160 mmHg or diastolic BP ≥ 95mmHg) despite medical treatment. Patients with a history of hypertension are allowed provided blood pressure is controlled by anti-hypertensive treatment.
- Clinically significant heart disease as evidenced by myocardial infarction or arterial thrombotic event within the past 6 months, severe or unstable angina, or New York Heart Association (NYHA) Class II-IV heart disease or cardiac ejection fraction measurement of < 50% at baseline
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- Screening ECG with rate-corrected (using Friderica's correction) QT interval (QTcF) of >480 msec or a history of cardiac arrythmias
- Refractory nausea and vomiting, requirement for parenteral hydration and/or nutrition, drainage gastrostomy tube, malabsorption, external biliary shunt, or significant small bowel resection that would preclude adequate study drug absorption
- Is pregnant or breastfeeding, and/or expecting to conceive within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
- Current use of estrogen or progesterone products including intrauterine and implantable contraceptive devices.
- Anticipated or ongoing administration of anti-cancer therapies other than those administered in this study
- Active Hepatitis B (HBsAg positive or hepatitis B virus DNA≥1×10^3 copy/ml) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
- Use of any prescription medication during the prior 28 days of first onapristone dosing that the investigator judges is likely to interfere with onapristone activity; specifically, strong inhibitors or inducers, or sensitive substrates of cytochrome P450 CYP3A4.
Trial locations and contacts
1 site in 1 country.
United States1 site
Memorial Sloan Kettering Westchester (All Protocol Activities)
Harrison, New York, 10604
About this study
Official title: ctDNA-guided Adaptive Therapy Escalation in ER+ MBC: A Phase 1b Study With Letrozole, Palbociclib and Onapristone ER
The researchers are doing this study to find out whether the study drug onapristone ER, combined with the standard treatment for your cancer (letrozole and palbociclib), is a safe treatment for people who have metastatic or unresectable ER+/PR+/HER2- breast cancer. The researchers will test different doses of the study drug to find the highest dose that causes few or mild side effects.
- Being tested
- Letrozole, Palbociclib, Onapristone ER
- Keywords
- ER+, PR+, HER2, Letrozole, Palbociclib, Onapristone, 21-194
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LetrozoleDrug
Letrozole will be given daily on days 1-28.
PalbociclibDrug
Palbociclib will be given daily on days 1-21 and held on days 22-28, as per standard FDA-approved dosing guidelines.
Onapristone ERDrug
Onapristone will be given daily on days 1-28.
| Study group | Role | What they receive |
|---|---|---|
| Letrozole, Palbociclib, and Onapristone ER | Experimental | This study has two stages: a dose-finding stage and a dose expansion stage. Stage 1 of the study will utilize a standard 3+3 dose de-escalation design with a total of three dose levels of onapristone ER, 30mg PO BID, 40mg PO BID, and 50mg PO BID given on a 28-day cycle. Onapristone ER will be given in addition to letrozole 2.5mg QD and each patient's pre-enrollment dose of palbociclib. Receives: Drug: Letrozole; Drug: Palbociclib; Drug: Onapristone ER |
What is being measured
The primary outcome is the main question the study is designed to answer.
recommended phase 2 dose (RP2D) of onapristone ER
The RP2D/MTD will be defined as the dose level at which a dose limiting toxicity (DLT) occurs in at most 1 out of 6 patients in that dose cohort.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 May 2021
- Study start9 Sep 2021
- Primary completion25 Apr 2023
- Study completion25 Apr 2023
Why it stopped: The sponsor closed the study due to discontinuing their onapristone program
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Breast CancerStudies of the same condition, open and under way.
- More trials run by Memorial Sloan Kettering Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Not applicable
- Intervention model
- Single group
- Model description
- This is an open label, single institution pilot phase 1b study of the oral progesterone antagonist, onapristone ER (Apristor), used as triplet escalation therapy patients with ER+/PR+/HER2- MBC who do not achieve mCR after six months (+/- 4 weeks) of treatment with letrozole and palbociclib in the first line.
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Context Therapeutics Inc.
- Responsible party
- Sponsor
- Investigators
- Komal Jhaveri, MD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04872608
- Sponsor's protocol ID
- 21-194
- Status last verified
- Apr 2023
- First submitted
- 29 Apr 2021
- Last updated
- 28 Apr 2023
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.
Study at a glance
From the registry record, last updated by the sponsor on 28 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- ctDNA-guided Adaptive Therapy Escalation in ER+ MBC: A Phase 1b Study With Letrozole, Palbociclib and Onapristone ER
- ClinicalTrials.gov ID
- NCT04872608
- Acronym / sponsor ID
- 21-194
- Keywords
- ER+, PR+, HER2, Letrozole, Palbociclib, Onapristone, 21-194
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: The sponsor closed the study due to discontinuing their onapristone program
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Collaborators
- Context Therapeutics Inc.
- Study start
- 9 Sep 2021 (actual)
- Primary completion
- 25 Apr 2023 (actual)
- Study completion
- 25 Apr 2023 (actual)
- First posted
- 4 May 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The researchers are doing this study to find out whether the study drug onapristone ER, combined with the standard treatment for your cancer (letrozole and palbociclib), is a safe treatment for people who have metastatic or unresectable ER+/PR+/HER2- breast cancer. The researchers will test different doses of the study drug to find the highest dose that causes few or mild side effects.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This is an open label, single institution pilot phase 1b study of the oral progesterone antagonist, onapristone ER (Apristor), used as triplet escalation therapy patients with ER+/PR+/HER2- MBC who do not achieve mCR after six months (+/- 4 weeks) of treatment with letrozole and palbociclib in the first line.
| Arm | Type | Receives |
|---|---|---|
| Letrozole, Palbociclib, and Onapristone ER | Experimental | Drug: Letrozole, Drug: Palbociclib, Drug: Onapristone ERThis study has two stages: a dose-finding stage and a dose expansion stage. Stage 1 of the study will utilize a standard 3+3 dose de-escalation design with a total of three dose levels of onapristone ER, 30mg PO BID, 40mg PO BID, and 50mg PO BID given on a 28-day cycle. Onapristone ER will be given in addition to letrozole 2.5mg QD and each patient's pre-enrollment dose of palbociclib. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (32 listed)
- Histologically confirmed ER+, PR+, HER2- metastatic or unresectable breast cancer
- Completed at least 6 months (+/- 4 weeks) of first-line letrozole/palbociclib without radiological progression or unresolved toxicity
- °Patients who underwent dose reduction of palbociclib to 100mg daily or 75mg daily will be eligible if:
- ctDNA-positive, defined as:
- °Presence of a tumor-derived somatic mutation in the peripheral blood using the MSK-ACCESS assay after 6 months of letrozole/palbociclib (+/- 4 weeks); at least one mutation should have avariant allele fraction of ≥ 0.5%
Key exclusion criteria (13 listed)
- Radiologic disease progression while on treatment with letrozole and palbociclib in the first line prior to enrollment
- History of another invasive malignancy (other than non-melanoma skin cancer or curatively treated in situ carcinoma) with evidence of disease within the past 3 years
- Any psychological, familial, sociological or geographic condition that would potentially hinder compliance with the study protocol
- Known untreated or symptomatic brain metastasis
- Uncontrolled hypertension (systolic BP ≥ 160 mmHg or diastolic BP ≥ 95mmHg) despite medical treatment. Patients with a history of hypertension are allowed provided blood pressure is controlled by anti-hypertensive treatment.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LetrozoleLetrozole will be given daily on days 1-28. | Drug | Letrozole, Palbociclib, and Onapristone ER |
| PalbociclibPalbociclib will be given daily on days 1-21 and held on days 22-28, as per standard FDA-approved dosing guidelines. | Drug | Letrozole, Palbociclib, and Onapristone ER |
| Onapristone EROnapristone will be given daily on days 1-28. | Drug | Letrozole, Palbociclib, and Onapristone ER |
Primary outcome
recommended phase 2 dose (RP2D) of onapristone ER
Time frame: 1 year
The RP2D/MTD will be defined as the dose level at which a dose limiting toxicity (DLT) occurs in at most 1 out of 6 patients in that dose cohort.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Apr 2023.
- Memorial Sloan Kettering Cancer CenterLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Komal Jhaveri, MD principal investigator
Memorial Sloan Kettering Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Letrozole, Palbociclib and Onapristone ER in people with Metastatic Breast Cancer and Unresectable Breast Cancer, run by Memorial Sloan Kettering Cancer Center 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 32 inclusion and 13 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 28 Apr 2023. 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?
recommended phase 2 dose (RP2D) of onapristone ER (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 28 Apr 2023.