Trial Search Results

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

The purpose of this study is to test the tolerability and efficacy or AZD0530 when used together with Anastrozole in patients with ER+ and/or PR+ postmenopausal breast cancer.

AZD0530 (also known as saracatinib), is an investigational drug which acts in a different way than Anastrozole or related drugs do. It blocks the action of an enzyme called SRC (pronounced “sark”). By doing this, AZD0530 also blocks some of the signals which are needed for the tumor to grow, spread, or become resistant to standard treatments such as Anastrozole. In this research study, AZD0530 is used before the time of primary surgery to remove the tumor. It is intended to improve and to aid the effectiveness of the standard hormonal therapy (Anastrozole) and surgery. The term “neoadjuvant” is commonly used to refer to treatment before the primary treatment of surgery.

Stanford is currently not accepting patients for this trial.

Lead Sponsor:

Joyce Marie Slingerland

Collaborator: Stanford University

Intervention(s):

  • Drug: Anastrozole
  • Drug: AZD0530
  • Drug: Placebo

Phase:

Phase 1/Phase 2

Eligibility


Inclusion Criteria - Phase 1 (Cohort A):

   - Female patient ≥ 18 years

   - Patient must be postmenopausal, verified by 1 of the following:

      - Bilateral surgical oophorectomy

      - No spontaneous menses > 1 year

      - No menses for < 1 year with FSH and estradiol levels in postmenopausal range

   - Postmenopausal women with primary invasive breast cancer, histologically confirmed by
   core needle (or incisional biopsy), whose tumors are estrogen (ER) and/or progesterone
   (PgR) positive. Estrogen- and/or progesterone-receptor positive disease based on 10%
   or more nuclear staining of the invasive component of the tumor

   - Stage IV disease (as defined by the AJCC Staging Manual, 6th Edition, 2002); or
   locally relapsed, unresectable disease

   - Measurable or evaluable disease according to RECIST criteria (see appendix VII)

   - Both HER2-positive and HER2-negative disease (as defined by IHC or by fluorescence in
   situ hybridization [FISH]). HER2+ must have had prior treatment with trastuzumab
   and/or lapatinib.

   - ECOG performance status 0-2 (see appendix VI)

   - Patients are suitable candidates for treatment with anastrozole (patients may have had
   any prior endocrine therapy or prior chemotherapy for treatment of their disease,
   either as adjuvant therapy, or as treatment for advanced disease). There is no
   restriction on the number of prior regimens in the phase I cohort A.

   - Patient is accessible and willing to comply with treatment and follow-up

   - Patient is willing to provide written informed consent prior to the performance of any
   study-related procedures

   - Required laboratory values

      - Absolute neutrophil count ≥ to 1.5 x 10^9/L

      - Hemoglobin ≥ to 9.0 g/dL

      - Platelet count ≥ to 100 x 10^9/L

      - Creatinine ≤ 1.5 mg/dL

      - Total bilirubin ≤ 1.0 x upper limit of normal (ULN)

      - Alkaline phosphatase and AST/ALT within protocol parameters. In determining
      eligibility, the more abnormal of the two values (AST or ALT) should be used.

Inclusion Criteria - Phase 2 (Cohort B):

   - Female patient ≥ 18 years

   - Patient must be postmenopausal, verified by 1 of the following:

      - Bilateral surgical oophorectomy

      - No spontaneous menses ≥ 1 year

      - No menses for < 1 year with FSH and estradiol levels in postmenopausal range

   - Postmenopausal women with primary invasive breast cancer, histologically confirmed by
   core needle (or incisional biopsy), whose tumors are estrogen (ER) and/or progesterone
   (PgR) positive. Estrogen- and/or progesterone-receptor positive disease based on 10%
   or more nuclear staining of the invasive component of the tumor. Patients may have
   bilateral or multifocal invasive breast cancers. The patient may have concurrent DCIS
   in either breast but the DCIS will not be measured as part of the study endpoints.

   - Tumor size ≥ 2 cm

   - Tumor measurable either by clinical examination, mammography, MRI, or ultrasound

   - HER2-negative disease (as defined by fluorescence in situ hybridization [FISH] or by
   IHC)

   - ECOG performance status 0-1 (see Appendix VI)

   - Patient is accessible and willing to comply with treatment and follow-up

   - Patient is willing to provide written informed consent prior to the performance of any
   study-related procedures

   - Required laboratory values

      - Absolute neutrophil count ≥ 1.5 x 10^9/L

      - Hemoglobin ≥ 9.0 g/dL

      - Platelet count ≥ 70 x 10^9/L

      - Creatinine ≤ 1.5 mg/dL

   - Total bilirubin ≤ 1.5 x upper limit of normal (ULN)

   - Alkaline phosphatase and AST/ALT ≤ 1.5 x upper limit of normal (ULN)

Exclusion Criteria - Phase 1 (Cohort A):

   - Concurrent therapy with any other non-protocol anti-cancer therapy

      - Any agent with estrogenic or putatively estrogenic properties, including herbal
      preparations, must be stopped at least one week prior to registration.

      - Ongoing, chronic administration of bisphosphonate therapy is allowed so long as
      such treatment was ongoing at the time of study entry.

   - Current therapy with hormone replacement therapy, or any hormonal agent such as
   raloxifene, tamoxifen, or other selective estrogen receptor modulators (agents must be
   stopped prior to randomization)

   - Presence of neuropathy ≥ grade 2 (NCI-CTC version 3.0) at baseline

   - History of any other malignancy within the past 5 years, with the exception of
   non-melanoma skin cancer or carcinoma-in-situ of the cervix

   - Clinically significant cardiovascular disease (e.g., hypertension [BP > 150/100],
   history of myocardial infarction or stroke within 6 months, unstable angina), New York
   Heart Association (NYHA) Grade II or greater congestive heart failure, or serious
   cardiac arrhythmia requiring medication

   - Active, uncontrolled infection requiring parenteral antimicrobials

   - A history of a severe hypersensitivity reaction to anastrozole, or AZD0530 or their
   excipients

   - Evidence of bleeding diathesis or coagulopathy.

   - Resting EKG with measurable QTc interval of >480msec at 2 or more time points within a
   24 hr period.

   - Since AZD0530 is a substrate and inhibitor of CYP3A4, patients requiring medication
   with drugs listed in Appendix XI should be excluded from study.

   - Any evidence of severe or uncontrolled systemic medical or psychiatric conditions
   (e.g. Severe hepatic impairment, interstitial lung disease [bilateral, diffuse,
   parenchymal lung disease]) or current unstable or uncompensated respiratory or cardiac
   conditions which make it undesirable for the patient to participate in the study or
   which could jeopardize compliance with the protocol

   - Evidence of underlying pulmonary dysfunction as evidenced by oxygen saturation <90% by
   pulse oximetry, interstitial pulmonary infiltrates on high resolution CT scan prior to
   study entry and/or symptomatic pulmonary (pleural or parenchymal) metastasis.

Exclusion Criteria - Phase 2 (Cohort B):

   - Prior chemotherapy, endocrine therapy or radiotherapy for the presenting breast
   cancer. Prior incidence and treatment of contralateral invasive or non-invasive breast
   cancer is not an exclusion criterion.

   - Inflammatory breast cancer, clinically defined as the presence of erythema or
   induration involving one-third or more of the breast, or pathologically defined as
   dermal lymphatic invasion

   - Prior excisional biopsy or complete resection of the primary invasive tumor (prior
   sentinel node biopsy allowed)

   - Prior ipsilateral radiation therapy for invasive or non-invasive breast cancer

   - Distant metastasis is an exclusion criterion - Isolated ipsilateral supraclavicular
   node involvement and/or direct invasion of the primary tumor into skin is allowed

   - Concurrent therapy with any other non-protocol anti-cancer therapy

   - Any agent with estrogenic or putatively estrogenic properties, including herbal
   preparations, must be stopped at least one week prior to registration

   - Current therapy with hormone replacement therapy, or any hormonal agent such as
   raloxifene, tamoxifen, or other selective estrogen receptor modulators (agents must be
   stopped for one week prior to randomization)

   - Presence of neuropathy ≥ grade 2 (NCI-CTC AE version 3.0) at baseline

   - History of any other malignancy within the past 5 years, with the exception of
   non-melanoma skin cancer or carcinoma-in-situ of the cervix

   - Clinically significant cardiovascular disease (e.g. history of myocardial infarction
   or stroke within 6 months, unstable angina), New York Heart Association (NYHA) Grade
   II or greater congestive heart failure, or serious cardiac arrhythmia requiring
   medication

   - Active, uncontrolled infection requiring parenteral antimicrobials

   - A history of a severe hypersensitivity reaction to anastrozole, or AZD0530 or their
   excipients

   - Evidence of bleeding diathesis or coagulopathy

   - Resting EKG with measurable QTc interval of >480msec at 2 or more time points within a
   24 hr period.

   - AZD0530 is a substrate and inhibitor of CYP3A4. Since concurrent administration of
   AZD0530 with other CYP3A4 substrates has been shown to be well tolerated, continuation
   or initiation of medically indicated drugs that are substrates of CYP3A4 is permitted
   at MD discretion. Drugs listed in Appendix XI that are known to strongly induce or
   inhibit CYP3A4 activity should be discontinued prior to study entry and should not be
   initiated during protocol treatment.

   - Any evidence of severe or uncontrolled systemic psychiatric or medical conditions (eg.
   Severe hepatic impairment, interstitial lung disease [bilateral, diffuse, parenchymal
   lung disease]) or current unstable or uncompensated respiratory or cardiac conditions
   which make it undesirable for the patient to participate in the study or which could
   jeopardize compliance with the protocol

   - Evidence of underlying pulmonary dysfunction as evidenced by oxygen saturation <90% by
   pulse oximetry prior to study entry and/or symptomatic pulmonary (pleural or
   parenchymal) disease.

   - Subjects unwilling or unable to undergo breast MRI as required by protocol will be
   excluded from study

Ages Eligible for Study

18 Years - N/A

Genders Eligible for Study

Female

Not currently accepting new patients for this trial

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
CCTO
650-498-7061
Not Recruiting