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Study of Radium-223 Dichloride Versus Placebo and Treatment With Exemestane / Everolimus in Subjects With Bone Predominant HER2 (Human Epidermal Growth Factor Receptor 2) Negative Hormone Receptor Positive Metastatic Breast Cancer

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ClinicalTrials.gov Identifier: NCT02258451
Recruitment Status : Active, not recruiting
First Posted : October 7, 2014
Last Update Posted : October 9, 2018
Sponsor:
Information provided by (Responsible Party):
Bayer

Brief Summary:
The objective of this study is to assess efficacy and safety of radium 223 dichloride in subjects with human epidermal growth factor receptor 2 (HER2) negative hormone receptor positive breast cancer with bone metastases treated with exemestane and everolimus.

Condition or disease Intervention/treatment Phase
Breast Neoplasms Drug: Radium-223 dichloride (Xofigo, BAY88-8223) Drug: Placebo (saline) Drug: Exemestane Drug: Everolimus Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 283 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase II Randomized, Double-blind, Placebo-controlled Trial of Radium-223 Dichloride in Combination With Exemestane and Everolimus Versus Placebo in Combination With Exemestane and Everolimus When Administered to Metastatic HER2 Negative Hormone Receptor Positive Breast Cancer Subjects With Bone Metastases
Actual Study Start Date : June 4, 2015
Estimated Primary Completion Date : July 31, 2019
Estimated Study Completion Date : July 31, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Radium-223 dichloride + exemestane/everolimus
Up to 6 cycles of radium-223 dichloride 50kBq/kg body weight (55 kBq/kg after implementation of National Institute of Standards and Technology [NIST] update) (randomized) + All patients will receive exemestane and everolimus
Drug: Radium-223 dichloride (Xofigo, BAY88-8223)
Up to 6 cycles of radium-223 dichloride 50kBq/kg body (55 kBq/kg after implementation of National Institute of Standards and Technology [NIST] update)

Drug: Exemestane
25 mg once daily with or without food Dosage and administration of exemestane must be in compliance with the local labels in each of the participating countries and in line with standard practice guidelines.

Drug: Everolimus
10 mg tablet once daily after a meal Dosage and administration of everolimus must be in compliance with the local labels in each of the participating countries and in line with standard practice guidelines.

Placebo Comparator: Placebo + exemestane/everolimus
Up to 6 cycles of saline injection (placebo) (randomized) + All patients will receive exemestane and everolimus
Drug: Placebo (saline)
Up to 6 cycles of saline injection

Drug: Exemestane
25 mg once daily with or without food Dosage and administration of exemestane must be in compliance with the local labels in each of the participating countries and in line with standard practice guidelines.

Drug: Everolimus
10 mg tablet once daily after a meal Dosage and administration of everolimus must be in compliance with the local labels in each of the participating countries and in line with standard practice guidelines.




Primary Outcome Measures :
  1. Symptomatic skeletal event free survival (SSE-FS). [ Time Frame: From time of randomization up to 26 months ]

Secondary Outcome Measures :
  1. Overall survival [ Time Frame: From time of randomization up to 26 months ]
  2. Time to opiate use for cancer pain [ Time Frame: From time of randomization up to 26 months ]
  3. Time to pain progression (only in subjects with baseline worst pain score (WPS) ≤8) [ Time Frame: From time of randomization up to 26 months ]
  4. Time to cytotoxic chemotherapy [ Time Frame: From time of randomization up to 26 months ]
  5. Radiological progression-free survival (rPFS) [ Time Frame: From time of randomization up to 26 months ]
  6. Frequency of abnormalities in laboratory examinations [ Time Frame: From time of randomization up to 26 months ]
  7. Pain improvement rate [ Time Frame: From time of randomization up to 26 months ]
  8. To measure new primary malignancies and hematopoietic reserve for tolerability of subsequent chemotherapy [ Time Frame: From time of randomization up to 26 months ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Women (≥18 years of age) with metastatic breast cancer not amenable to curative treatment by surgery or radiotherapy.
  • Documentation of histological or cytological confirmation of estrogen receptor positive (ER+) and HER2 negative adenocarcinoma of the breast must be available.
  • Documentation of menopausal status: postmenopausal subjects or pre-menopausal subjects with ovarian radiation or concomitant therapy with a luteinizing hormone-releasing hormone (LH-RH) agonist/antagonist are eligible.
  • Subjects with bone dominant disease with at least 2 skeletal metastases identified at baseline by bone scintigraphy and confirmed by computed tomography (CT)/magnetic resonance imaging (MRI).
  • Subjects must have received at least one line of hormonal therapy in the metastatic setting.
  • Subjects who are eligible as per the Investigator's assessment and according to the local label for treatment with exemestane and everolimus as a second line or greater of hormone therapy in a metastatic setting.
  • Subjects must have experienced recurrent/progressive disease following treatment with a non-steroidal aromatase inhibitor (letrozole or anastrozole) in an adjuvant or metastatic setting
  • Subjects must have experienced no more than two skeletal-related events (SREs) prior to study entry defined as: need for external beam radiotherapy (EBRT) to bone pain, pathological bone fracture (excluding major trauma), spinal cord compression and/or orthopedic surgical procedure. Subjects with no prior SREs are not permitted.
  • Subjects must be on therapy with bisphosphonates or denosumab for at least 1 month before start of study treatment.
  • Adequate hematological, liver and kidney function.

Exclusion Criteria:

  • Subjects with Inflammatory breast cancer.
  • Patients with immediately life-threatening visceral disease for whom chemotherapy is preferred treatment option.
  • Subjects who have either received chemotherapy for metastatic disease or are considered by the treating investigator to be appropriate candidates for chemotherapy as current treatment for metastatic breast cancer are excluded. Chemotherapy administered for adjuvant/neo adjuvant disease is acceptable provided it was administered at least 1 year prior to study entry.
  • Subjects who received prior treatment or are already receiving everolimus treatment prior to study entry are not eligible.
  • Subjects with known or history of brain metastases or leptomeningeal disease: subjects with neurological symptoms must undergo a contrast CT scan or MRI of the brain within 28 days prior to randomization to exclude active brain metastasis. Imaging of the central nervous system (CNS) is otherwise not required.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02258451


  Show 137 Study Locations
Sponsors and Collaborators
Bayer
Investigators
Study Director: Bayer Study Director Bayer

Additional Information:
Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT02258451     History of Changes
Other Study ID Numbers: 17096
2014-002114-23 ( EudraCT Number )
First Posted: October 7, 2014    Key Record Dates
Last Update Posted: October 9, 2018
Last Verified: October 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Bayer:
Breast Cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Hormones
Exemestane
Radium Ra 223 dichloride
Everolimus
Sirolimus
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists