Neoplasms

Symptoms and General Pathology

All Conditions

Skin and Connective Tissue Diseases

Neoplasm Metastasis

Breast Neoplasms

Breast Diseases

Skin Diseases

All Drugs and Chemicals

Antineoplastic Agents

Hormones

Estrogens

Anastrozole

Aromatase Inhibitors

Progesterone

Saracatinib

Antineoplastic Agents, Hormonal

Enzyme Inhibitors

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormone Antagonists

Dual treatment with 1 mg anastrozole orally once daily together with AZD0530 (saracatinib) 175 mg orally once daily, or as specified per protocol, until disease progression for treatment of metastatic breast cancer

Dual treatment with 1 mg anastrozole orally once daily together with AZD0530 (saracatinib) 175 mg orally once daily, or as specified per protocol, until disease progression or 4-6 months of treatment completed.

Dual treatment with 1 mg anastrozole orally once daily together with Placebo orally once daily, or as specified per protocol, until disease progression or4-6 months of treatment completed.

AZD0530 (saracatinib)

Placebo

Joyce Slingerland, MD

The investigators propose to conduct a Phase I/randomized Phase II study design in order to test the tolerability and efficacy of AZD0530 (also called saracatinib) when used together with anastrozole in therapy for ER+ and/or PR+, postmenopausal breast cancer. The Phase I pharmacokinetic (PK) cohort of the study (cohort A) in postmenopausal women with metastatic breast cancer 2008-2009 showed initial safety,tolerability and good bioavailability of both drugs and determined the doses for use in the ongoing Phase II trial. In the randomized Phase II cohort of the study (cohort B), postmenopausal women with newly diagnosed, previously untreated ER+, HER2 negative breast cancer that is at least 2 cm or more in diameter by clinical exam or radiology will be randomized to either neoadjuvant treatment with anastrozole plus placebo, or anastrozole in combination with AZD0530 (saracatinib). The Phase II cohort will permit extended assays of tolerability, initial estimates of efficacy, and the investigation of molecular predictors of drug efficacy.

A Pharmacokinetic and Randomized Trial of Neoadjuvant Treatment With Anastrozole Plus AZD0530 in Postmenopausal Patients With Hormone Receptor Positive Breast Cancer

A Phase I Pharmacokinetic and Randomized Phase II Trial of Neoadjuvant Treatment With Anastrozole Plus AZD0530 in Postmenopausal Patients With Hormone Receptor Positive Breast Cancer

To identify a well tolerated dose of AZD0530 (saracatinib) that can be used together with anastrozole in the Phase 2 trial with tolerable toxicity and PK, subjects were followed as AEs recorded and evaluated and drug concentrations were in the therapeutic range.

Clinical response is defined as percentage change in tumor size calculated from bi-dimensional clinical tumor measurement at diagnosis and on completion of neoadjuvant treatment. The mean reduction in tumor size ( +/-SD) will be derived form the change in largest tumor dimension ( RECIST) and by calculated tumor volume

Summarized as mean plasma concentrations (ng/ml) of each drug (AZD0530 (saracatinib) and Anastrozole) after exposure to dual therapy.

Summarized as the geometric means and standard deviations for the corresponding for peak plasma concentration of each study drug ( AZD0530 (saracatinib) and anastrozole) after exposure

MRI will be used to compare tumor size at baseline and at 10 weeks. MRI will also be used to compare tumor size at baseline and after completion of 6 months of study medication or disease progression.

A pathologic complete response will be defined as the absence of viable tumor cells in the resected specimen, as determined by standard histologic examination. All specimens will be reviewed by a central pathologist to determine pathologic response.

Based on physician measurement of tumor size and by MRI measurements of tumor volume using RECIST criteria

Blood draws at protocol-specified timepoints to determine mean blood levels of drug for each of AZD0530 and Anastrozole.

Cinically significant AEs defined as clinically significant changes in the patient's symptoms, physical examination and clinical laboratory results are reported as toxicity for AZD0530 (saracatinib) given with anastrozole and for anastrozole given with placebo

Stanford University

Joyce Marie Slingerland

Professor

Dual treatment with 1 mg anastrozole orally once daily together with AZD0530 175 mg orally once daily, or as specified per protocol, until disease progression for treatment of metastatic breast cancer

Anastrozole

AZD0530

Phase 1 - Cohort A

Dual treatment with 1 mg anastrozole orally once daily together with AZD0530 175 mg orally once daily, or as specified per protocol, until disease progression or 4-6 months of treatment completed.

Anastrozole

AZD0530

Phase 2 - Cohort B [Anastrozole + AZD0530]

Dual treatment with 1 mg anastrozole orally once daily together with Placebo orally once daily, or as specified per protocol, until disease progression or4-6 months of treatment completed.

Anastrozole

Placebo

Phase 2 - Cohort B [Anastrozole + Placebo]

Total

Age, Categorical

Sex: Female, Male

Race/Ethnicity

Race/Ethnicity, Customized

For the Phase 1 cohort, all 12/12 planned subjects were accrued. Of the planned 60 subjects for Phase 2, 59 subjects were accrued. One was removed from study within a few days ( MD discretion) and is not included in subsequent analysis.

Joyce Slingerland MD PhD FCRP(C)

anastrozole

saracatinib

Phase I Cohort A: Maximum Tolerated AZD0530 Daily Dose Used in Combination With Daily Oral Anastrozole

Max clinical diameter % change

Clinical tumor volume% change

Of 59 subjects, 2 (one/arm)tumors were not palpable at baseline; 1 was removed at MD discretion; 8 removed due to AEs . 48 (30+18) completed 4 mo of therapy and were evaluable for clinical response. Subjects completing 4 months were permitted to go tor surgery. At 24 weeks 19 dual and 16 monotherapy remained evaluable for clinical tumor size.

Phase II - Cohort B: Compare Treatment Groups (AZD0530 + Anastrozole Versus Anastrozole With Placebo) With Respect to Clinical Response

AZD0530 - Cycle 1: 0 hrs

AZD0530 - Cycle 1: 6 hrs

AZD0530 - Cycle 1: 12 hrs

AZD0530 - Cycle 1: 24 hrs

AZD0530 - Cycle 1: 48 hrs

AZD0530 - Cycle 1: 72 hrs

AZD0530 - Day 8

AZD0530 - Day 15

AZD0530 - Day 22

Anastrozole - Day 1: 0 hrs

Anastrozole - Day 1: 6 hrs

Anastrozole - Day 1: 12 hrs

Anastrozole - (24 hrs)

Anastrozole - (48 hrs)

Anastrozole - (72 hrs)

Anastrozole - Day 8

Anastrozole - Day 15

Anastrozole - Day 22

Dual treatment with 1 mg anastrozole orally once daily given for 7 days followed by anastrozole 1 mg orally once daily together with AZD0530 175 mg orally once daily, or as specified per protocol, until disease progression for treatment of metastatic breast cancer.

Anastrozole

AZD0530

Phase I - Cohort A: Plasma Concentrations of AZD0530 (Saracatinib) and Anastrozole

AZD0530 (saracatinib) ng/ml

anastrozole ng/ml

Phase 1-Cohort A: Peak Concentration of Each Study Drug ( AZD0530 (Saracatinib) and Anastrozole)

MRI RECIST % change 10 weeks

MRI tumor volume % change 10 weeks

MRI RECIST % change 6 months

MRI tumor volume % change 6 months

Of 59 subjects, 1 was removed at MD discretion; 8 removed due to AEs. Of the remaining 50 (31 dual + 19 mono), all had MRI at 10 weeks. 3 dual and 1 mono had disease progression and no further MRIs. 7 out of 28 (dual) \& 2 out 18 (mono) completing 4 months, had end of study MRI at wk 18; 21 ( dual) and 16 (mono) had a final MRI at 24 weeks .

Phase II Cohort B: Change in Tumor Size by Comparison of Serial MRI

Phase II - Cohort B: Number of Participants With Pathologic Complete Response (pCR)

Complete Response

Partial Response

Stable Disease

Disease Progression

8 patients were removed from the study due to adverse events

Phase II - Cohort B: The Number of Participants Achieving Clinical Benefit Defined as Complete Response (CR), or Partial Response (PR) or Stable Disease (SD)

Anastrozole - Day 28

Anastrozole - Day 56

Anastrozole - Day 84

AZD0530 - Day 28

AZD0530 - Day 56

AZD0530 - Day 84

PK assays of AZD0530 could not be completed for all participants due to technical problems with the assay protocol

Phase II - Cohort B: To Report the Pharmacokinetics (Mean Blood Levels of Drug) of AZD0530 (Saracatinib) and Anastrozole

Anemia

Neutropenia

Thrombocytopenia

Fatigue

Rash

Alopecia

Hot Flashes

Anorexia

Diarrhea

Alanine aminotransferase increased

Alkaline phosphatase increased

Aspartate aminotransferase increased

Creatinine increased

Hyperbilirubinemia

Flu-like syndrome

Upper Respiratory Infection

Urinary Tract Infection

Phase II - Cohort B: Treatment Emergent Adverse Events Associated With AZD0530 (Saracatinib) Given With Anastrozole and of Anastrozole Given With Placebo

Overall Study

Fulvestrant

Mitogens

Combination therapy with cabozantinib 60 mg daily plus fulvestrant 500 mg monthly Intramuscularly (IM)

Cabozantinib

Steven J Isakoff, MD, PhD

The study drug cabozantinib works by inhibiting several different proteins which are believed to be involved in breast cancer tumor growth, its ability to spread, and its ability to form new blood vessels. This drug has been used in other research studies and information from those other research studies suggests that this drug may help to prevent cancer growth.

The single agent portion of this study is now closed to accrual. This research study is now examining the efficacy of cabozantinib in combination with fulvestrant for treatment of hormone-receptor-positive breast cancer that has spread to bone.

Cabozantinib will be taken orally once a day in cycles of 28 days (4 weeks). Fulvestrant will be given intramuscularly on days 1 and 15 of cycle 1 and on day 1 of all subsequent cycles.

On Day 1 of each cycle subjects will have the following tests and procedures:

* Performance status
* Physical exam
* Vital signs
* Routine blood samples
* Blood and urine samples to look at bone markers (Cycle 1 through 6 only)

Subjects will also have the following additional tests and procedures:

* Tumor assessment by Computed Tomography (CT) scan and bone scan at Cycle 3, then every 12 weeks
* Blood or urine pregnancy test (if applicable) on Day 1 of Cycles 1, 2, 4, then every 12 weeks
* Urine sample and blood test for thyroid function (Cycle 1, 3, 5, then every 6 weeks)
* Blood test for breast cancer tumor marker (Cycle 1 and 4, then every 6 weeks)
* Pain questionnaire and painkiller medication diary at 7-day intervals during Week 3, Week 6, and every 6 weeks thereafter.

Cabozantinib in Women With Metastatic Hormone-Receptor-Positive Breast Cancer

A Phase II Trial of Cabozantinib in Women With Metastatic Hormone-Receptor-Positive Breast Cancer With Involvement of Bone

To evaluate the bone scan response rate in patients with hormone-receptor-positive breast cancer with bone metastases receiving cabozantinib. Bone scan response rate will be defined as the percentage of patients experiencing a complete resolution or significant improvement in the bone scan.

To evaluate overall response rate (ORR) (defined as the percentage of patients experiencing a complete response or partial response)

Exelixis

Massachusetts General Hospital

Principal Investigator, Attending Physician in Medical Oncology

1mg daily for two weeks in the interval between diagnostic breast biopsy and definitive breast surgery.

1mg PO daily for two weeks prior to scheduled surgery

Katherine Crew, MD

The purpose of this study is to determine the feasibility of a short term administration of a targeted therapy (i.e., anastrozole) in women with newly diagnosed early invasive or non invasive breast cancer during the interval between their breast biopsy and surgery. Anastrozole is a form of hormonal therapy which is part of the standard treatment for hormone sensitive breast cancer in postmenopausal women. This clinical model is being used to evaluate the biologic effects of this drug on a specific molecular pathway called the PI3K/AKT signaling pathway.

Several clinical models are being explored for use in the phase I/II evaluation of targeted therapies for breast cancer. Biological markers can be measured in early stage invasive cancers in a presurgical model involving a short term intervention. In this model, women with newly diagnosed early invasive breast cancer receive a study drug during the interval between diagnostic breast biopsy and surgical resection. Tumor tissue obtained from the biopsy and surgical specimens are used to measure pre and post treatment molecular markers, respectively. The main advantages of this model include the ability to obtain direct information on molecular response in tumor tissue and elucidate drug mechanisms of action, the large patient population to draw from with early stage breast cancer, and the lack of unnecessary invasive procedures.

We plan to conduct a pilot study of 10 postmenopausal women with newly diagnosed estrogen receptor (ER) positive invasive or non invasive breast cancer who will receive oral anastrozole 1mg daily for two weeks in the interval between diagnostic breast biopsy and definitive breast surgery. Patients will be identified by the breast surgeon or mammographer performing the breast biopsy. Patients with histologically confirmed ER+ invasive or non invasive breast cancer will be recruited by the medical oncologist and will start anastrozole two weeks prior to their scheduled surgery. The primary objective of this study is to demonstrate the feasibility of this presurgical model for evaluating targeted therapies for breast cancer. Secondary endpoints include changes in tissue levels of the proliferation marker Ki67 and proteins involved in PI3K/AKT signaling.

Pre-Surgical Intervention for Targeted Therapies for Breast Cancer

Feasibility of Pre-Surgical Intervention Studies for Evaluating Targeted Therapies for Breast Cancer

The number of subjects who complete oral anastrozole for the length of the study is analyzed. The subjects receive oral anastrozole 1mg daily for two weeks in the interval between the biopsy and the surgery.

Avon Foundation

Columbia University

Assistant Professor of Medicine and Assistant Professor of Epidemiology

1mg daily for two weeks in the interval between diagnostic breast biopsy and definitive breast surgery.

Anastrozole: 1mg PO daily for two weeks prior to scheduled surgery

Presurgical Oral Anastrozole

Age, Continuous

United States

Region of Enrollment

Dr. Katherine Crew

Number of Subjects That Completed Oral Anastrozole 1mg Daily for Two Weeks in the Interval Between Diagnostic Breast Biopsy and Definitive Breast Surgery

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Pharmacokinetic and Randomized Trial of Neoadjuvant Treatment With Anastrozole Plus AZD0530 in Postmenopausal Patients With Hormone Receptor Positive Breast Cancer	NCT01216176	Breast Cancer	Anastrozole AZD0530 (saraca... Placebo	18 Years -	University of Miami
Cabozantinib in Women With Metastatic Hormone-Receptor-Positive Breast Cancer	NCT01441947	Breast Cancer	Cabozantinib Fulvestrant	18 Years -	Massachusetts General Hospital
Pre-Surgical Intervention for Targeted Therapies for Breast Cancer	NCT01004744	Invasive Breast...	Anastrozole	21 Years -	Columbia University
Pre-Surgical Intervention for Targeted Therapies for Breast Cancer	NCT01004744	Invasive Breast...	Anastrozole	21 Years -	Columbia University

Spots Global Cancer Trial Database for pr+

Every month we try and update this database with for pr+ cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for pr+

Every month we try and update this database with for pr+ cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for pr+ cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.