Clinical Trials /

PalbocIclib in PreMenopausal Women With ER Positive/HER-2 Negative MetAstatic Breast Cancer

NCT02917005

Description:

This is an open label, randomized, multicenter, international phase II study for premenopausal patients with hormone receptor positive, HER2 negative metastatic or locally advanced breast cancer. Patients will be randomized to receive either palbociclib + exemestane + OFS (Arm 1) or exemestane +OFS (Arm 2). Treatment will be continued until disease progression, unacceptable toxicities, or withdrawal of consent.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: PalbocIclib in PreMenopausal Women With ER Positive/HER-2 Negative MetAstatic Breast Cancer
  • Official Title: A Phase II Study of Ovarian Function Suppression And ExemesTane With or Without PalbocIclib in PreMenopausal Women With ER Positive / HER-2 Negative MetAstatic Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: AMCI-001
  • NCT ID: NCT02917005

Conditions

  • Metastatic Breast Cancer

Interventions

DrugSynonymsArms
PalbociclibIbrancePalbociclib Arm
ExemestaneAromasinePalbociclib Arm
GoserelinZoladexPalbociclib Arm

Purpose

This is an open label, randomized, multicenter, international phase II study for premenopausal patients with hormone receptor positive, HER2 negative metastatic or locally advanced breast cancer. Patients will be randomized to receive either palbociclib + exemestane + OFS (Arm 1) or exemestane +OFS (Arm 2). Treatment will be continued until disease progression, unacceptable toxicities, or withdrawal of consent.

Detailed Description

      There is a strong in-vitro and clinical evidence suggesting that the dual inhibition of CDK
      4/6 and ER signaling is a highly effective therapeutic strategy in HR+ MBC. With the
      unprecedented success of palbociclib in PALOMA-1 trial, several phase 2 and 3 trials are
      underway to evaluate this agent (and other CDK4/6 inhibitors as well) in the different
      clinical scenarios of HR+ breast cancer [28].The vast majority of these trials -if not all-
      are testing these novel agents in postmenopausal patients, which would render the clinical
      experience of these agents restricted to postmenopausal women (median age was 62 years in
      PALOMA-1 trial) The scarcity of clinical trials addressing endocrinal therapy in
      premenopausal women with MBC is, at least in part, related to the fact that the majority of
      women in western countries are diagnosed with breast cancer during their postmenopausal life.
      However the situation is rather different in many countries, including those in the Middle
      East region, where the median age of women diagnosed with breast cancer is below 50 years,
      and where approximately 50% of these patients are still menstruating.

      This study will be the first to explore the therapeutic effects of palbociclib when combined
      with exemestane and ovarian function suppression (OFS) in premenopausal with hormone receptor
      positive and HER2 negative MBC, and how it will compare to the classic approach of using OFS
      plus an aromatase inhibitor.
    

Trial Arms

NameTypeDescriptionInterventions
Palbociclib ArmExperimentalPalbociclib (Pfizer) 125mg/day orally for 3 weeks followed by 1 week off plus Exemestane (Pfizer) 25mg/day orally continuously plus Goserelin (Astrazeneca) 3.6 mg SC given every 28 days
  • Palbociclib
  • Exemestane
  • Goserelin
Control ArmActive ComparatorExemestane (Pfizer) 25mg/day orally continuously plus Goserelin (Astrazeneca) 3.6 mg SC given every 28 days
  • Exemestane
  • Goserelin

Eligibility Criteria

        Inclusion Criteria:

          1. Adult women (≥ 18 years of age) with metastatic or locally advanced breast cancer
             (histologically or cytologically proven diagnosis of adenocarcinoma of the breast) not
             amenable to curative treatment by surgery or radiotherapy.

          2. ER positive tumour: Histological or cytological confirmation of estrogen and/or
             progesterone-receptor positive, as determined by routine IHC. Positivity is defined as
             ≥1% positive stained cells. The receptor status determined by utilizing an assay
             consistent with local laboratory standards.

          3. HER2 negative breast cancer as confirmed by IHC, SISH or FISH.

          4. Premenopausal women : (definition of a real menopause is not a simple task in these
             relatively young women, owing to the potential effect of prior chemotherapy and /or
             endocrinal therapy particularly OFS) defined either by:

             i. Any age below 40 years , irrespective to E2 level or menstrual history ii. If the
             woman had a menstrual period any time within the last 12 months iii. If the woman has
             amenorrhea of more than 12 months (in the absence of chemotherapy or ovarian function
             suppression) that is associated with serum hormone levels that are NOT in the
             postmenopausal range (either estradiol (E2) < 30 pg/mL and follicle-stimulating
             hormone (FSH) < 20 mU/mL OR E2 ≥ 30 pg/mL and FSH ≥ 20 mU/mL) [30].

          5. Secondary hormonal resistance to tamoxifen or endocrinal sensitive metastatic disease
             i. Secondary hormonal resistance is defined as recurrence after 24 months from the
             start of adjuvant tamoxifen treatment or within 12 months from the end of the 5 years
             of adjuvant Tamoxifen ii. Endocrinal sensitive disease is defined as recurrence after
             12 months from the end of adjuvant tamoxifen treatment or de novo metastatic disease

          6. Measurable disease according to RECIST or bone-only metastases. Previously irradiated
             lesions are deemed measurable only if progression is documented at the site after
             completion of radiation.

             i. Patients must either have at least one lesion that can be accurately measured; OR
             ii. Patients have bone lesions: lytic or mixed (lytic + sclerotic) in the absence of
             measurable disease as defined above.

          7. ECOG Performance Status 0, 1, & 2.

          8. Resolution of all acute toxic effects of prior therapy or surgical procedures to
             National Cancer Institute (NCI) CTCAE Grade 1 (except alopecia or other toxicities not
             considered a safety risk for the patient).

          9. Adequate organ function as defined by the following criteria:

             i. Absolute neutrophil count (ANC) ≥ 1.5 10˄9/L ii. Platelets > 100 x10˄9/L iii.
             Hemoglobin (Hgb) > 9.0g/dL iv. INR < 2 v. Serum aspartate aminotransferase (AST) and
             alanine aminotransferase (ALT) < 2.5x ULN (or <5 if hepatic metastases are present)
             vi. Total serum bilirubin < 1.5 x ULN (<3 x ULN for patients known to have Gilberts
             Syndrome) vii. Serum creatinine < 1.5 x ULN viii. QTc< 470 msec (based on the mean
             value of the triplicate ECGs).

         10. Written informed consent obtained before any trial related activity and according to
             local guidelines.

        Exclusion Criteria:

          1. Postmenopausal women. Postmenopausal status is defined by age>40years with amenorrhea
             of more than 12 months, associated with serum hormonal levels of the postmenopausal
             range (either estradiol (E2) < 30 pg/mL and follicle-stimulating hormone (FSH) < 20
             mU/mL or E2 ≥ 30 pg/mL and FSH ≥ 20 mU/mL) [30], in the absence of chemotherapy,
             tamoxifen, or OFS.

          2. Patients with primary endocrinal resistance, defined as recurrence within 24 months
             from the start of adjuvant tamoxifen treatment.

          3. Symptomatic and/or life threatening visceral metastases i. Diffuse lymphangitic
             carcinomatosis. ii. Bulky liver or pulmonary metastases

          4. Patients with only non-measurable lesions other than bone metastasis as defined above
             (e.g., pleural effusion, ascites, etc.).

          5. Patients who have received hormonal treatment other than neo/adjuvant tamoxifen

             ± LHRH agonist for their early breast cancer.

          6. Patients who received prior chemotherapy for metastatic or recurrent breast cancer.

          7. Another malignancy within 5 years prior to enrolment with the exception of adequately
             treated in-situ carcinoma of the cervix, uterus, basal or squamous cell carcinoma or
             non-melanomatous skin cancer.

          8. Uncontrolled (clinically or radiologically progressive) CNS metastases, carcinomatous
             meningitis, or leptomeningeal disease.

          9. Major surgery within 3 weeks of first study treatment.

         10. Chemotherapy, radiotherapy, or other anti-cancer therapy within 2 weeks before
             randomization. Patients who previously received radiotherapy to 25% of bone marrow are
             not eligible independent of when it was received.

         11. Current treatment with any anti-cancer therapies for advanced disease; any
             experimental treatment of another clinical trial; therapeutic doses of anticoagulant.

             N.B. Low dose anticoagulants for deep vein thrombosis prophylaxis are allowed. Low
             molecular weight heparin is allowed. Aspirin is permitted.

         12. Active bleeding diathesis.

         13. History of non-compliance to medical regimens. Patients unwilling to or unable to
             comply with the protocol.

         14. Pregnant or breast feeding women or those who are not using effective birth control
             methods. Adequate contraceptives must be used throughout the trial and for 8 weeks
             after the last study drug administration. Patients must have a negative serum
             pregnancy test within 7 days prior to first administration of study drug.

         15. Prior hematopoietic stem cell or bone marrow transplantation.

         16. Current use of food or drugs known to be potent CYP3A4 inhibitors, drugs known to be
             potent CYP3A4 inducers, and drugs that are known to prolong the QT interval.

         17. Known or possible hypersensitivity to goserelin during the adjuvant setting.

         18. Any severe and/or uncontrolled medical conditions such as:

             i. Unstable angina pectoris, symptomatic congestive heart failure, myocardial
             infarction < 6months prior to enrollment, serious uncontrolled cardiac arrhythmia ii.
             Uncontrolled diabetes as defined by fasting serum glucose > 3 x ULN iii. Acute and
             chronic active infectious disorders (except for Hepatitis B and Hepatitis C positive
             patients) and non-malignant medical illnesses that are uncontrolled or whose control
             may be jeopardized by the complications of this study therapy iv. Known human
             immunodeficiency virus infection v. Impairment of gastrointestinal function or
             gastrointestinal disease that may significantly alter the absorption of study drugs
             (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption
             syndrome)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression free survival
Time Frame:28 months
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Overall response rate
Time Frame:28 months
Safety Issue:
Description:
Measure:Clinical benefit rate
Time Frame:28 months
Safety Issue:
Description:
Measure:Overall survival
Time Frame:52 months
Safety Issue:
Description:
Measure:Incidence of treatment related adverse events
Time Frame:28 months
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Hamdy A. Azim

Trial Keywords

  • breast cancer
  • hormone receptor positive, HER2 negative
  • palbociclib
  • premenopausal

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