A Phase 3 interventional study of Letrozole SIE + Ribociclib + Oral placebo and Oral Femara® + Ribociclib + Injectable placebo in Advanced, Metastatic Breast Cancer, sponsored by Rovi Pharmaceuticals Laboratories. Not yet recruiting. Open to female participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-04-02.
Sponsored by Rovi Pharmaceuticals Laboratories · Phase 3, Interventional, and Treatment
The purpose of this study is to evaluate the efficacy and safety of Letrozole SIE (injectable) compared to Femara® (oral tablet), both given together with ribociclib, for the first-line treatment of postmenopausal women with HR-positive, HER2-negative, inoperable locally advanced or metastatic breast cancer.
This is a multicenter, randomized, double-blind, double-dummy, active-controlled Phase III study comparing Letrozole SIE with Femara® (both in combination with the CDK4/6 inhibitor ribociclib) in postmenopausal women with HR-positive, HER2-negative, inoperable locally advanced or metastatic breast cancer. The study employs double-blinding with matching placebos (double-dummy technique) to minimize bias on the part of participants, investigators, and analysts. Participants will be randomized in a 1:1 ratio to receive either Letrozole SIE (experimental use) or Femara® (active comparator), both in combination with the CDK4/6 inhibitor ribociclib. Randomization occurs after Screening and confirmation of eligibility and will be stratified by visceral metastasis (Yes/No) and prior adjuvant endocrine therapy (Yes/No).
The Treatment Period will last from Cycle 1 Day 1 (C1D1) until study intervention discontinuation due to disease progression, symptomatic deterioration, unacceptable toxicity, withdrawal of consent, loss to follow-up, participant's death, or end of study, whichever occurs first. After study intervention discontinuation, a post-discontinuation visit will be performed. Then, participants will be followed until withdrawal of consent, loss to follow-up, the participant's death, or end of study, whichever occurs first.
14,829 studies on the registry are indexed under Breast Neoplasms; 3,318 are open to participants now.
This study's planned enrollment of 300 is above the median of 72 across 10,900 interventional studies indexed under Breast Neoplasms.
Browse Breast Neoplasms studies →Rovi Pharmaceuticals Laboratories is the lead sponsor of 19 studies on the registry; 2 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Use of the following medications within the 3 previous days or a period of 5 half-lives, (whichever is longer) prior to randomization:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
HER2 is a protein, made from the ERBB2 gene, that drives the growth of some cancers. A study may look for a level of the protein, extra copies of the gene, or a particular change in it.
In breast cancer, protein tests are read as HER2-positive, HER2-low or HER2-negative; other cancers use their own rules. Check which test result the study requires.
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Neoadjuvant treatment is given before the main treatment (usually surgery), often to shrink a tumour. Adjuvant treatment is given after it, to lower the chance of the cancer coming back.
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
The US National Cancer Institute’s scale of how severe an adverse event is — any unwanted medical event during a study, such as a symptom, an illness or an abnormal test result, whether or not a treatment caused it. Whether it did is judged separately.
“Side effects of earlier treatment resolved to grade 1 or less” means they have settled to mild or gone.
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HER2
HER2 is a protein, made from the ERBB2 gene, that drives the growth of some cancers. A study may look for a level of the protein, extra copies of the gene, or a particular change in it.
In breast cancer, protein tests are read as HER2-positive, HER2-low or HER2-negative; other cancers use their own rules. Check which test result the study requires.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Postmenopausal
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Adjuvant and neoadjuvant
Neoadjuvant treatment is given before the main treatment (usually surgery), often to shrink a tumour. Adjuvant treatment is given after it, to lower the chance of the cancer coming back.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Measurable disease
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CTCAE grade
The US National Cancer Institute’s scale of how severe an adverse event is — any unwanted medical event during a study, such as a symptom, an illness or an abnormal test result, whether or not a treatment caused it. Whether it did is judged separately.
“Side effects of earlier treatment resolved to grade 1 or less” means they have settled to mild or gone.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
BMI (body mass index)
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECG (electrocardiogram)
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CYP3A (CYP3A4) inhibitors and inducers
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Drug: Letrozole SIE + Ribociclib + Oral placebo
Drug: Oral Femara® + Ribociclib + Injectable placebo
Letrozole SIE quarterly (injectable) + Ribociclib once daily (oral) + placebo once daily (oral)
Femara® 2.5 mg/day (oral) + Ribociclib once daily (oral) + placebo quarterly (injectable)
This study also gives Ribociclib. No intervention listed here names it: that was found by reading the record.
Progression Free Survival (PFS)
PFS per Investigator assessment, defined as the time from the date of randomization to the date of the first documented progression or death due to any cause. PFS will be assessed via a local radiology assessment according to RECIST v1.1. PFS as assessed through a blinded independent central review will be used for supportive evidence of the primary efficacy endpoint.
Time frame: From the date of randomization to the date of the first documented progression or death due to any cause, assessed according to RECIST version 1.1 (up to approximately 30 months).
Overall Survival (OS): Primary analysis
OS, defined as the time from the date of randomization to date of death from any cause.
Time frame: From the date of randomization to date of death from any cause (up to approximately 30 months).
Overall Survival (OS): Final analysis
OS, defined as the time from the date of randomization to date of death from any cause.
Time frame: From the date of randomization to date of death from any cause (up to approximately 88 months).
Objective Response Rate (ORR)
ORR, defined as the proportion of participants with a best overall response of complete response (CR) or partial response (PR) by Investigator assessment per RECIST v1.1 criteria.
Time frame: From the date of randomization to the date of the first documented progression or death due to any cause, assessed according to RECIST version 1.1 (up to approximately 30 months).
Incidence of arthralgias/arthritis and/or myalgias
To compare the incidence rate of a combined event of arthralgias/arthritis and/or myalgias between Letrozole SIE and Femara®
Time frame: From the date of the first dose of study intervention to the post-discontinuation visit (up to approximately 30 months).
Time to Response (TTR)
TTR, defined for participants with complete response or partial response defined by Investigator assessment per RECIST v1.1 criteria as the interval between randomization and the earliest documentation of response.
Time frame: From the date of randomization to the date of the first documented evidence of complete response or partial response (up to approximately 30 months).
Duration of response (DOR)
DOR, defined for those participants with complete response (CR) or partial response (PR) as the time from first documented evidence of CR or PR until disease progression by Investigator assessment per RECIST v1.1 criteria, or death from any cause, whichever occurs first.
Time frame: From first documented evidence of complete response (CR) or partial response (PR) until disease progression or death from any cause, whichever occurs first (up to approximately 30 months).
Clinical benefit rate (CBR)
CBR, defined as the proportion of participants with complete response (CR), partial response (PR), or stable disease (SD) ≥ 6 months according to Investigator assessment per RECIST v1.1 criteria.
Time frame: From the date of randomization to the date of the first documented progression or death due to any cause, assessed according to RECIST version 1.1 (up to approximately 30 months).
Time to treatment failure (TTF)
TTF, defined as the time from randomization to study intervention discontinuation for any reason.
Time frame: From date of randomization to study intervention discontinuation for any reason (up to approximately 30 months).
Change from baseline in the FACT-G total score
To compare the health-related quality of life between Letrozole SIE and Femara® (both in combination with the CDK4/6 inhibitor ribociclib) using FACT-G questionnaire. FACT is a modular approach to assess participant health-related quality of life using a 'core' set of questions (FACT-G) as well as a cancer site-specific module. The FACT-G is a 27-item compilation of general questions divided into 4 domains: Physical Well-Being, Social/Family Well-Being, Emotional Well-Being, and Functional Well-Being. For all questions, participants are asked to respond to a five-level scale where 0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, and 4=very much.
Time frame: From the date of randomization to the post-discontinuation visit (up to approximately 30 months).
Change from baseline in the FACT-G Physical well-being subscale score
To compare the health-related quality of life between Letrozole SIE and Femara® (both in combination with the CDK4/6 inhibitor ribociclib) using FACT-G subscales.
Time frame: From the date of randomization to the time of disease progression (up to approximately 30 months).
Change from baseline in the FACT-G Social/Familiy well-being subscale score
To compare the health-related quality of life between Letrozole SIE and Femara® (both in combination with the CDK4/6 inhibitor ribociclib) using FACT-G subscales.
Time frame: From the date of randomization to the time of disease progression (up to approximately 30 months).
Change from baseline in the FACT-G Emotional well-being subscale score
To compare the health-related quality of life between Letrozole SIE and Femara® (both in combination with the CDK4/6 inhibitor ribociclib) using FACT-G subscales.
Time frame: From the date of randomization to the time of disease progression (up to approximately 30 months).
Change from baseline in the FACT-G Functional well-being subscale score
To compare the health-related quality of life between Letrozole SIE and Femara® (both in combination with the CDK4/6 inhibitor ribociclib) using FACT-G subscales.
Time frame: From the date of randomization to the post-discontinuation visit (up to approximately 30 months).
Change from baseline in the FACT-B total score
To compare the health-related quality of life between Letrozole SIE and Femara® (both in combination with the CDK4/6 inhibitor ribociclib) using FACT-B questionnaire. FACT is a modular approach to assess participant health-related quality of life using a 'core' set of questions (FACT-G) as well as a cancer site-specific module. The FACT-G is a 27-item compilation of general questions divided into 4 domains: Physical Well-Being, Social/Family Well-Being, Emotional Well-Being, and Functional Well-Being. The FACT-B consists of the FACT-G and a breast-specific module: a 10-item instrument designed to assess participant concerns relating to breast cancer. For all questions, participants were asked to respond to a five-level scale where 0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, and 4=very much.
Time frame: From the date of randomization to the post-discontinuation visit (up to approximately 30 months).
Change from baseline in the FACT-B Breast Cancer subscale score
To compare the health-related quality of life between Letrozole SIE and Femara® (both in combination with the CDK4/6 inhibitor ribociclib) using the FACT-B questionnaire.
Time frame: From the date of randomization to the post-discontinuation visit (up to approximately 30 months).
Change from baseline in the FACT-ES total score
To compare the health-related quality of life between Letrozole SIE and Femara® (both in combination with the CDK4/6 inhibitor ribociclib) using the FACT-ES questionnaire. FACT is a modular approach to assess participant health-related quality of life using a 'core' set of questions (FACT-G) as well as a cancer site-specific module. The FACT-G is a 27-item compilation of general questions divided into 4 domains: Physical Well-Being, Social/Family Well-Being, Emotional Well-Being, and Functional Well-Being. FACT-ES incorporates 19 additional items that assess endocrine related symptoms in addition to the FACT-G core items. For all questions, participants were asked to respond to a five-level scale where 0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, and 4=very much.
Time frame: From the date of randomization to the post-discontinuation visit (up to approximately 30 months).
Change from baseline in the FACT-ES Endocrine Symptoms subscale score
To compare the health-related quality of life between Letrozole SIE and Femara® (both in combination with the CDK4/6 inhibitor ribociclib) using the FACT-ES questionnaire.
Time frame: From the date of randomization to the post-discontinuation visit (up to approximately 30 months).
Time to deterioration in the FACT-G total score
Deterioration will be defined as the time from the date of randomization to the first occurrence of a decrease from baseline of at least 5 points for FACT-G total score.
Time frame: From the date of randomization to to the first occurrence of a decrease from baseline of at least 5 points for FACT-G (up to approximately 30 months).
Time to deterioration in the FACT-B total score
Deterioration will be defined as the time from the date of randomization to the first occurrence of a decrease from baseline of at least 7 points for FACT-B total score.
Time frame: From the date of randomization to to the first occurrence of a decrease from baseline of at least 7 points for FACT-B (up to approximately 30 months).
Time to deterioration in the FACT-ES total score
Deterioration will be defined as the time from the date of randomization to the first occurrence of a decrease from baseline of at least 7 points for FACT-ES total score.
Time frame: From the date of randomization to to the first occurrence of a decrease from baseline of at least 7 points for FACT-ES (up to approximately 30 months).
ESR1 mutation status
Percentage of participants with ESR1 mutations at the time of disease progression among those without ESR1 mutations at baseline.
Time frame: From the date of randomization to the time of disease progression (up to approximately 30 months).
ESR1 mutant allele frequency
ESR1 mutant allele frequency at the time of disease progression.
Time frame: At the time of disease progression (up to approximately 30 months).
Incidence of Adverse Events (AEs)
AEs type, severity, seriousness, and relationship to study intervention, including the incidence of TEAEs, the incidence of serious TEAEs, and the incidence of TEAEs leading to study intervention discontinuation.
Time frame: From the Informed Consent Form signature to the post-discontinuation visit (approximately up to 88 months).
Incidence of injection site reactions
Injection site redness, swelling, and induration will be evaluated before and after Letrozole SIE or injectable placebo administration.
Time frame: From the date of the first dose of study intervention to the post-discontinuation visit (approximately up to 88 months).
Changes in injection-related pain score
Injection site pain, self-assessed by participants using an numeric rating scale (NRS) at the time of Letrozole SIE or injectable placebo administration and for a longer period of time if necessary. The numeric rating scale (NRS) evaluates the intensity of injection-related pain experienced at the time of Letrozole SIE/injectable placebo administration. It is scored from 0 to 10 (0 meaning no pain and 10 meaning the worst possible pain).
Time frame: From the date of the first dose of study intervention to the post-discontinuation visit (approximately up to 88 months).
Change from baseline in Bone mineral density (BMD)
Change from baseline in BMD assessed by DXA
Time frame: From the Informed Consent Form signature to the post-discontinuation visit (approximately up to 30 months).
No study locations are listed for this record.
Start is estimated for Aug 2026; primary completion for Feb 2029, 30 months later.
Of 272 industry-sponsored phase 3 interventional studies under Breast Neoplasms, half reached primary completion within 40 months of starting (the median), counting those still running; a quarter within 28 and three quarters within 63. This study's planned 30 months is below that.
Counting every sponsor, half of 600 studies reached it within 59 months; a quarter within 36 and three quarters within 96.
How these figures are worked out, and which studies are left out of them.
This study is not yet recruiting, as verified in Mar 2026. You cannot join it, but the record below documents what was studied.
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Rovi Pharmaceuticals Laboratories