CompletedNCT00338728Updated Jan 27, 2020Results posted

Letrozole and Imatinib Mesylate in Treating Postmenopausal Participants With Estrogen or Progesterone Positive Metastatic Breast Cancer

A Phase 2 interventional study of Imatinib Mesylate and Letrozole in Anatomic Stage IV Breast Cancer AJCC v8, Estrogen Receptor Positive and KIT Positive, sponsored by M.D. Anderson Cancer Center. Completed at 1 site in United States. Open to female participants. Per ClinicalTrials.gov, last updated 2020-01-27.

Sponsored by M.D. Anderson Cancer Center · Phase 2, Interventional, and Treatment

From the registry’s dates

Registered 2 years 8 months after the study started (first participant enrolled Oct 2003, registered Jun 2006).

Phase: Phase 2
Study type: Interventional
Enrollment: 59
Allocation: Not applicable
Sex: Female

Study summary

This phase II trial studies the side effects and how well letrozole and imatinib mesylate work in treating postmenopausal participants with estrogen or progesterone positive breast cancer that has spread to other places in the body. Letrozole is an antihormonal drug used in the standard treatment of hormonal sensitive breast cancer. Imatinib mesylate is a drug that binds to certain proteins on the tumor cells and prevents them from further growth. Imatinib mesylate is thought to prevent the potential resistance to letrozole, which may make the letrozole more effective. Giving letrozole and imatinib mesylate may work better in treating participants with breast cancer.

Read the detailed description

PRIMARY OBJECTIVES:

I. To determine the efficacy of letrozole plus imatinib mesylate in patients with estrogen receptor (ER) and or progesterone receptor (PgR) positive metastatic breast cancer.

II. To determine the safety and tolerability of letrozole plus imatinib mesylate in patients with metastatic breast cancer.

III. To determine the time to disease progression and overall survival in patients with metastatic breast cancer who are treated with letrozole plus imatinib mesylate.

OUTLINE:

Participants receive imatinib mesylate orally (PO) twice daily (BID) and letrozole PO once daily (QD) for 8 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, participants are followed up at 1 and 4 weeks and at 2, 4, 6, 9, and 12 months.

Conditions studied

Anatomic Stage IV Breast Cancer AJCC v8
Estrogen Receptor Positive
KIT Positive
PDGFR Positive
Postmenopausal
Progesterone Receptor Positive
Prognostic Stage IV Breast Cancer AJCC v8

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Breast Neoplasms 12,544

In context

Breast Neoplasms

12,544 studies on the registry are indexed under Breast Neoplasms; 2,892 are open to participants now.

This study's enrollment of 59 is below the median of 72 across 9,303 interventional studies indexed under Breast Neoplasms.

Browse Breast Neoplasms studies →

Lead sponsor

M.D. Anderson Cancer Center is the lead sponsor of 2,999 studies on the registry; 581 are open to participants now.

Of its 599 completed or terminated interventional studies of FDA-regulated products, 402 (67%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: Child (0–17), Adult (18–64), Older adult (65+)
Sexes eligible: Female
Accepts healthy volunteers: No

Inclusion criteria

Postmenopausal women able to comply with the protocol requirements with metastatic breast cancer, whose tumors are estrogen (ER) and/or progesterone (PgR) positive, defined by core biopsy immunohistochemistry with greater than 10% positive malignant epithelial cells
Patients must have documented expression of either PDGFR or CD117 (c-kit) by immunohistochemistry
Patients may have received tamoxifen in the adjuvant/neoadjuvant or setting. Patients may have previously received chemotherapy in the adjuvant/ neoadjuvant setting, though this is not required. Prior chemotherapy for metastatic breast cancer is allowed. Concomitant bisphosphonates are allowed for patients with bone metastases and who have another site of measurable disease
Post menopausal status defined by one of the following: no spontaneous menses for at least 1 year, in women greater than or equal to 55 years spontaneous menses within the past 1 year in women greater than or equal to 55 years with postmenopausal gonadotrophin levels (luteinizing hormone [LH] and follicle stimulating hormone [FSH] levels greater than 40 IU/L ) or postmenopausal estradiol levels (less than 5 mg/dl) or according to the definition of "postmenopausal range" for the laboratory involved bilateral oophorectomy
Performance status, Eastern Cooperative Oncology Group (ECOG) greater than or equal to 2
Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as greater than or equal to 10 mm with conventional techniques. Bone disease only will not be accepted as measurable disease. Pleural or peritoneal effusions will not be accepted as measurable disease
Absolute neutrophil count (ANC) = 1.5 x 10 to the 9th power/L
Platelets greater than or equal to 100.0 x 10 to the 9th power/L
Hemoglobin greater than 10.0 g/dL
Creatinine less than 1.5 mg/dl
Total (T.) bilirubin less than 1.5 x normal
Aspartate aminotransferase (AST) less than 2.5 x normal
A life expectancy of at least 6 months
Localized radiotherapy, which does not influence the signal of evaluable lesion, is allowed prior to the initiation of imatinib mesylate. Patients must have recovered from the myelosuppressive effects of previous radiotherapy (at least 2-4 weeks)
Ability to understand and the willingness to sign a written informed consent

Exclusion criteria

Exclusion Criteria:

Prior treatment with Femara or Gleevec
Uncontrolled endocrine disorders such as diabetes mellitus, confirmed hypo- or hyperthyroidism, Cushing's syndrome, Addison's disease (treated or untreated)
Patients with unstable angina, or uncontrolled cardiac disease (e.g. class III or IV New York Heart Association's functional classification)
Other concurrent malignant disease with the exception of cone-biopsied in situ carcinoma of the cervix uteri, or adequately treated basal or squamous cell carcinoma of the skin, or other curable cancers e.g. Hodgkin's disease or non-Hodgkin lymphoma (NHL), provided 5 years have elapsed from completion of therapy, and there has been no recurrence
Concomitant treatment with steroids, e.g. glucocorticoids for indications other than cancer, except aerosol for obstructive airways diseases and steroid injection to the joints for treatment of inflammation
Other investigational drugs within the past 3 weeks and the concomitant use of investigational drugs
History of non-compliance to medical regimens and patients who are considered potentially unreliable
Patients with known brain metastasis
Patients with known chronic liver disease (i.e., chronic active hepatitis, and cirrhosis)
Patients with known diagnosis of human immunodeficiency virus (HIV) infection
Patients who received chemotherapy within 4 weeks (6 weeks for nitrosourea or mitomycin-C) prior to study entry, unless the disease is rapidly progressing
Patients who previously received radiotherapy to greater than or equal to 25% of the bone marrow
Patients who had a major surgery within 2 weeks prior to study entry

Study design

Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrollment: 59 participants (actual)

Study arms

Experimental
Treatment (imatinib mesylate, letrozole)
Participants receive imatinib mesylate PO BID and letrozole PO QD for 8 weeks in the absence of disease progression or unacceptable toxicity.
Drug: Imatinib Mesylate · Drug: Letrozole

Interventions

DrugImatinib Mesylate
Given PO
Also known as: CGP 57148, CGP57148B, Gleevec, Glivec, STI 571, STI-571, STI571
DrugLetrozole
Given PO
Also known as: CGS 20267, Femara

What researchers measure

Primary outcomes

Objective Response Rate (ORR)
Among participants with CR or PR as the best overall response, duration of response (DOR) was defined as the time from which measurement criteria were met for CR or PR until the date of progression. Progression-free survival (PFS) was defined as the time from study enrollment to disease progression or death from any cause, whichever occurred first. PFS data were censored at the time of removal from study. Overall survival (OS) was defined as the time from study registration to death from any cause. Information on vital status was collected following study completion through July 23, 2018 and was used in the determination of OS. Among patients with SD as the best overall response, duration of SD was defined as the time from study enrollment to disease progression or removal from study.
Time frame: From the registration until disease progression, death, unacceptable toxicity, or withdraw of study consent, whichever occurred first assessed up to 182 months
Overall Survival of Participants
This sample size would provide an estimate of the objective response rate (ORR) 95% confidence intervals for the ORR and CBR were calculated using the exact binomial method. Among patients with CR or PR as the best overall response, duration of response (DOR) was defined as the time from which measurement criteria were met for CR or PR until the date of progression. Progression-free survival (PFS) was defined as the time from study enrollment to disease progression or death from any cause, whichever occurred first. PFS data were censored at the time of removal from study. Overall survival (OS) was defined as the time from study registration to death from any cause. Information on vital status was collected following study completion through July 23, 2018 and was used in the determination of OS. Among patients with SD as the best overall response, duration of SD was defined as the time from study enrollment to disease progression or removal from study.
Time frame: From the registration until disease progression, death, unacceptable toxicity, or withdraw of study consent, whichever occurred first assessed up to 182 months

Results

Posted Jan 27, 2020

Participant flow

Participants were recruited from November 2003 to October 2008. The participating subjects must sign the consent document pertaining to the study and meet all the eligibility criteria as mentioned in the protocol, before initiating on the study treatment.

Participant flow — Overall Study
Milestone	Letrozole and Imatinib Mesylate
Started	59
Completed	45
Not completed	14
Withdrew: Screen failure	14

Outcome measures

PrimaryObjective Response Rate (ORR)

Among participants with CR or PR as the best overall response, duration of response (DOR) was defined as the time from which measurement criteria were met for CR or PR until the date of progression. Progression-free survival (PFS) was defined as the time from study enrollment to disease progression or death from any cause, whichever occurred first. PFS data were censored at the time of removal from study. Overall survival (OS) was defined as the time from study registration to death from any cause. Information on vital status was collected following study completion through July 23, 2018 and was used in the determination of OS. Among patients with SD as the best overall response, duration of SD was defined as the time from study enrollment to disease progression or removal from study.

Time frame:: From the registration until disease progression, death, unacceptable toxicity, or withdraw of study consent, whichever occurred first assessed up to 182 months
Reported as:: Count of participants · Participants

Objective Response Rate (ORR)
Participants	Letrozole and Imatinib Mesylate
Complete Response (CR)	0
Partial Response (PR)	5
SD (including non-CR/Non-PD)>/=24 weeks	16
SD (including non-CR/Non-PD)</=24 weeks	8
Progressive Disease	11
Non-Evaluable	5

PrimaryOverall Survival of Participants

This sample size would provide an estimate of the objective response rate (ORR) 95% confidence intervals for the ORR and CBR were calculated using the exact binomial method. Among patients with CR or PR as the best overall response, duration of response (DOR) was defined as the time from which measurement criteria were met for CR or PR until the date of progression. Progression-free survival (PFS) was defined as the time from study enrollment to disease progression or death from any cause, whichever occurred first. PFS data were censored at the time of removal from study. Overall survival (OS) was defined as the time from study registration to death from any cause. Information on vital status was collected following study completion through July 23, 2018 and was used in the determination of OS. Among patients with SD as the best overall response, duration of SD was defined as the time from study enrollment to disease progression or removal from study.

Time frame:: From the registration until disease progression, death, unacceptable toxicity, or withdraw of study consent, whichever occurred first assessed up to 182 months
Reported as:: Median · months

Overall Survival of Participants
months	Letrozole and Imatinib Mesylate
Progression-free survival (PFS)	8.7 (3.8 to 11.4)
Overall Survival (OS)	44.3 (34 to 55.3)

Adverse events

Collected over From the registration until disease progression, death, unacceptable toxicity, or withdraw of study consent, whichever occurred first assessed up to 182 months. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Letrozole and Imatinib Mesylate	0/45 (0%)	14/45 (31.1%)	45/45 (100%)

Most frequent serious events

Most frequent serious events
Event	Letrozole and Imatinib Mesylate
DiarrheaGastrointestinal disorders	7/45
FatigueGeneral disorders	3/45
NeutropeniaBlood and lymphatic system disorders	2/45
MyalgiaMusculoskeletal and connective tissue disorders	1/45
Elevated bilirubinInvestigations	1/45

Most frequent other events

Showing 10 of 31

Most frequent other events
Event	Letrozole and Imatinib Mesylate
FatigueGeneral disorders	23/45
NauseaGastrointestinal disorders	19/45
VomittingGastrointestinal disorders	17/45
AnemiaBlood and lymphatic system disorders	11/45
Diarrhea (grade 2)Gastrointestinal disorders	10/45
EdemaInvestigations	10/45
MyalgiaMusculoskeletal and connective tissue disorders	10/45
HeartburnGastrointestinal disorders	6/45
NeutropeniaBlood and lymphatic system disorders	6/45
PruritisSkin and subcutaneous tissue disorders	6/45

Baseline characteristics

Age, Continuous
Age, Continuous(years)	Letrozole and Imatinib Mesylate
Median	62.4 (41.4 to 82.7)

Sex: Female, Male
Sex: Female, Male(Participants)	Letrozole and Imatinib Mesylate
Female	45
Male	0

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	Letrozole and Imatinib Mesylate
Hispanic or Latino	6
Not Hispanic or Latino	39
Unknown or Not Reported	0

Region of Enrollment
Region of Enrollment(Participants)	Letrozole and Imatinib Mesylate
United States	45

Study locations

1 site

M D Anderson Cancer Center
Houston, Texas 77030, United States

References and documents

Study documents

Protocol and statistical analysis plan · Aug 7, 2009

Documents are hosted by the registry — open the source record to download them.

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Jan 27, 2020, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT00338728
Lead sponsor: M.D. Anderson Cancer Center
Collaborators: National Cancer Institute (NCI)
Responsible party: Sponsor
First posted: Jun 20, 2006
Start date: Oct 3, 2003
Primary completion: Nov 27, 2018
Completion: Nov 27, 2018
Results posted: Jan 27, 2020
Last update: Jan 27, 2020

Study contacts

Banu Arun

principal investigator · M.D. Anderson Cancer Center

Oversight

Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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