PALbociclib rechallenge in hormone receptor-posItive/HER2-negative advanced breast cancer (PALMIRA)

Phase 1

• Conditions: Hormone receptor-positive/HER2-negative Advanced Breast Cancer; MedDRA version: 21.1Level: LLTClassification code 10072737Term: Advanced breast cancerSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2017-002781-48-DE
• Lead Sponsor: Medica Scientia Innovation Research (MedSIR)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-02-15
• Last Update Posted: 8 October 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Female
• Target Recruitment: 198

Inclusion Criteria

1.- Female patients #18 years of age. 2.- Pre-menopausal (treated with a LHRH analogue for at least 28 days) or post-menopausal women. 3.- ECOG 0 - 1. 4.- Life expectancy #12 weeks. 5.- ABC not amenable to curative treatment. 6.- HR-positive and/or HER2-negative. 7.- Disease progression on first-line combination of palbociclib + endocrine therapy (AI or fulvestrant). 8.- Clinical benefit to a first-line palbociclib-based endocrine regimen. 9.- Previous palbociclib dose: min 75mg during the last 2 cycles. 10.- Last dose of palbociclib administered not later than 8 weeks and not earlier than 7 days from study entry, (except in the adjuvant setting).
11.- Patients should not have been treated in the advanced setting with at least one of these endocrine therapy options: either fulvestrant or AI. Note: Patients treated with adjuvant AI with a disease- free interval # 12 months, and with first-line fulvestrant in the metastatic setting, could receive treatment with an AI in themetastatic setting. 12.- Measurable or evaluable disease acc. RECIST v.1.1.
Patients with only bone lesions are eligible. 13.- Tumor tissue biopsy (if feasible) from a metastatic site or the primary breast tumor, both at inclusion and after disease progression for exploratory studies. If not feasible, eligibility to be evaluated by Sponsor’s designee. 14.- Patients agree to collection of blood samples (liquid biopsy) at inclusion, after 2 weeks of treatment, and upon progression or study termination. 15.- Adequate organ function. 16.- Patients who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures. 17.- Patients informed and signed informed consent. 18.- Resolution of all acute toxic effects of prior anti- cancer therapy to grade
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 50
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 148

Exclusion Criteria

1. HR or HER2 unknown disease. 2. HER2-positive disease based on local laboratory results (performed by IHC / ISH test). 3. Locally ABC candidate for curative treatment.4. Formal contraindication to endocrine therapy defined as visceral crisis and rapidly or symptomatic progressive visceral disease. 5. Prior therapy with any other CDK4/6 inhibitor different from palbociclib. 6. Known active uncontrolled or symptomatic Central Nervous System (CNS) metastases, carcinomatous meningitis, or leptomeningeal disease as indicated by clinical symptoms, cerebral edema, and/or progressive growth. Patients with a history of CNS metastases or cord compression are eligible if they have been definitively treated (e.g., radiotherapy, stereotactic surgery) and are clinically stable off anticonvulsants and steroids for at least 4 weeks before randomization. 7. Patients are currently receiving food or drugs known to be strong inducers or inhibitors of CYP3A4 (see Section 3.5 for details on prohibited medications). 8. Current or prior malignancy which could affect compliance with the protocol or interpretation of results. Patients with curatively- treated non-melanoma skin cancer, non-muscle-invasive bladder cancer, or carcinoma in situ, among others, are generally eligible. 9. No other systemic therapy for metastatic disease including chemotherapy, immunotherapy, targeted therapy (small molecules/ monoclonal antibodies), or endocrine therapy excluding first-line palbociclib-based regimen. 10. Major surgery (defined as requiring general anesthesia) or significant traumatic injury within 2 weeks of start of study drug, or patients who have not recovered from the side effects of any major surgery, or patients who may require major surgery during the study. 11. Radiotherapy or limited-field palliative radiotherapy within 7 days prior to study enrolment, or patients who have not recovered from radiotherapy-related toxicities to baseline or grade # 1 and/or from whom # 25% of the bone marrow has been previously irradiated. 12. Use of concurrent investigational agents or other concomitant anticancer therapies. 13. Active bleeding diathesis, previous history of bleeding diathesis, or chronic anti-coagulation treatment (the use of low molecular weight heparin is allowed as soon as it is used as prophylaxis intention). 14. Serious concomitant systemic disorder (e.g., active infection including HIV, or cardiac disease) incompatible with the study (at the discretion of investigator). 15. Unable to swallow capsules or tablets. 16. History of malabsorption syndrome or other condition that would interfere with enteral absorption. 17. Any of the following within 6 months of randomization: myocardial infarction, severe/unstable angina, ongoing cardiac dysrhythmias of NCI-CTCAE v.5.0 grade #2, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident including transient ischemic attack, or symptomatic pulmonary embolism. 18. Uncontrolled electrolyte disorders of NCI-CTCAE v.5.0 grade #2. 19. Known hypersensitivity to palbociclib or any of its excipients.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified