A Randomized, Open Label, Phase III Trial to Evaluate the Efficacy and Safety of Palbociclib + Anti-HER2 Therapy + Endocrine Therapy vs. Anti-HER2 Therapy + Endocrine Therapy after Induction Treatment for Hormone Receptor Positive (HR+)/HER2-Positive Metastatic Breast Cancer

Phase 1

• Conditions: Metastatic carcinoma, hormone receptors positive and HER2-positive; MedDRA version: 23.0Level: PTClassification code 10065430Term: HER2 positive breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: LLTClassification code 10027475Term: Metastatic breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 23.0Level: LLTClassification code 10070575Term: Estrogen receptor positive breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2017-000419-17-IT
• Lead Sponsor: Alliance Foundation Trials (AFT)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-01-29
• Last Update Posted: 5 April 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 496

Inclusion Criteria

Signed Informed Consent Form obtained prior to any study specific assessments and procedures
Age =18 years
Participants must have histologically confirmed invasive breast cancer that is metastatic or not amenable for resection or radiation therapy with curative intent. Histological documentation of metastatic/recurrent breast cancer is not required if there is unequivocal evidence for recurrence of the breast cancer.
Patients must have histologically confirmed HER2+ and ER+ and/or PR+, metastatic breast cancer.
ECOG performance status 0-1
Patients must be able and willing to swallow and retain oral medication without a condition that would interfere with enteric absorption.
Serum or urine pregnancy test must be negative within 7 days in women of childbearing potential. Women of childbearing potential and male patients must use adequate contraception for the duration of protocol treatment and for 6 months after the last treatment with palbociclib
Resolution of all acute toxic effects of prior induction anti-HER2-based chemotherapy regimen to NCI CTCAE version 4.0 Grade =1
Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures
Patients may or may not have received neo/adjuvant therapy, but must have a disease-free interval from completion of anti-HER2 therapy to metastatic diagnosis =6 months.
Patients must have received an acceptable, standard, chemotherapy containing anti-HER2 based induction therapy for the treatment of metastatic breast cancer. CT is limited to a taxane or vinorelbine (only for trastuzumab-based regimen). Eligible patients are expected to have completed 6 cycles of chemotherapy containing anti-HER2-therapy treatment. A min of 4 cycles of treatment is acceptable for patients experiencing significant toxicity associated with treatment as long as they are without evidence of disease progression (i.e. CR, PR or SD). The max number of cycles is 8. Patients are eligible provided they are without evidence of disease progression by local assessment (i.e. CR, PR or SD).
Participants with a history of treated CNS metastases are eligible, if Disease outside the CNS is present; No evidence of interim progression between the completion of CNS directed therapy and the screening radiographic study; No history of intracranial hemorrhage or spinal cord hemorrhage; Not requiring anti-convulsants for symptomatic control;Min of 3 weeks between completion of CNS radiotherapy and Cycle 1 Day 1 and recovery from significant (G = 3) acute toxicity with no ongoing requirement for corticosteroid
Neutrophil = 1,000/mm3
Platelets = 100,000/mm3
Hb = 10g/dL
Total bilirubin = ULN; or total bilirubin = 3.0 × ULN with direct bilirubin within normal range in patients with documented Gilbert’s Syndrome.
AST or ALT = 3 × institutional ULN (=5 x ULN if liver metastases are present).
Creatinine within normal institutional limits or creatinine clearance = 60 mL/min/1.73 m2 for patients with serum creatinine levels above institutional ULN.
LVEF > 50%
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 340
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 156

Exclusion Criteria

Randomization
1.Concurrent therapy with other Investigational Products.
2.Prior therapy with any CDK 4/6 inhibitor.
3.History of allergic reactions attributed to compounds of chemical or biologic composition similar to palbociclib.
4.Patients receiving any medications or substances that are strong inhibitors or inducers of CYP3A isoenzymes within 7 days of randomization (see Section 8.6.3 for list of strong inhibitors or inducers of CYP3A isoenzymes).
5.Uncontrolled current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, diabetes, or psychiatric illness/social situations that would limit compliance with study requirements. Ability to comply with study requirements is to be assessed by each investigator at the time of screening for study participation.
6.Pregnant women, or women of childbearing potential without a negative pregnancy test (serum or urine) within 7 days prior to randomization, irrespective of the method of contraception used, are excluded from this study because the effect of palbociclib on a developing fetus is unknown. Breastfeeding must be discontinued prior to study entry.
7.Patients on combination antiretroviral therapy, i.e. those who are HIV-positive, are ineligible because of the potential for pharmacokinetic interactions or increased immunosuppression with palbociclib.
8.QTc interval >480 msec, Brugada syndrome or known history of QTc prolongation or Torsade de Pointes.
9.Patients with clinically significant history of liver disease, including viral or other known hepatitis, current alcohol abuse, or cirrhosis

Study & Design

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