PAveMenT: Phase Ib Study of Palbociclib and Avelumab in Metastatic AR+ Triple Negative Breast Cancer
This clinical study is aiming to determine the safest doses and schedule for the combination of two drugs named palbociclib and avelumab. The study will also be investigating how effective the combination is for a subgroup of breast cancer patients whose cancer expresses the androgen receptor (AR) but not the oestrogen (hormone) or HER2 receptors. Palbociclib is a drug used in routine care for hormone-receptor (HR) positive and HER2 negative advanced breast cancer, the most common subtype of breast cancer. It is possible that the combination of palbociclib and avelumab will be a more effective cancer treatment than each drug separately, but this is unknown and this study is needed to establish the best dosage and schedule of each drug as well as how effective the combination is.
• Patients with recurrent inoperable locally advanced or metastatic breast cancer.
• Previously treated with at least one prior line of chemotherapy for advanced disease, but no more than two prior lines of chemotherapy for advanced disease. Patients with ER+ breast cancer must have received at least one prior line of hormone therapy for advanced disease. Patients with HER2+ breast cancer must have received at least one prior line of HER2 directed therapy.
• Measurable disease (RECIST 1.1)
• Haematological and biochemical indices within the ranges stated in the study protocol. These measurements must be performed within one week (Day -7 to Day 1) before the patient goes in the trial.
• Women/female patients with child-bearing potential (defined as the fertile status following menarche and until becoming post-menopausal unless permanently sterile by methods that include hysterectomy, bilateral salpingectomy and bilateral oophorectomy) must have a negative urine or serum pregnancy test within 7 days prior to start of trial.
• Women/females of child bearing potential or their male partners must use a highly effective method of contraception for 2 weeks before starting the study treatment, throughout the treatment period and for 1 month after discontinuation of treatment with palbociclib and avelumab (women/female patients) or 14 weeks (men/male patients). Highly effective methods are defined as methods that can achieve a failure rate of less than 1% per year when used consistently and correctly are considered as highly effective birth control methods, such methods include:
⁃ Oral, intra-vaginal or transdermal combined hormonal contraception
⁃ Oral, injectable or implantable progesterone-only contraception
⁃ Intrauterine device
⁃ Intrauterine hormone-releasing system,
⁃ Bilateral tubal occlusion
⁃ Vasectomised partner
⁃ True abstinence:\* When this is in line with the preferred and usual lifestyle of the subject
• Key: \* it is only considered highly effective if the patient is refraining from sexual intercourse during the entire period of risk associated with the study treatments
• 18 years of age or over.
• World Health Organisation (WHO) performance status 0 or 1
• Estimated life expectancy of at least 3 months in the opinion of the investigator
• Signed and dated informed consent.
⁃ Patients willing and able to comply with scheduled visits, treatment plans, laboratory tests, follow up and other procedures
• Patients with recurrent inoperable locally advanced or metastatic AR+ triple negative breast cancer with ER, PgR and HER2 status determined locally and AR determined centrally on archival metastatic tissue. Archival tissue from the primary tumour (which must have been ER/PgR negative and collected within 5 years prior to metastatic relapse) may be used for AR testing if no archival metastatic tissue is available.
• Previously treated with at least one prior line of chemotherapy for advanced disease, but no more than two prior lines of chemotherapy for advanced disease.
• Measurable disease (RECIST 1.1) amenable to fresh biopsy
• Haematological and biochemical indices within the ranges stated in the study protocol. These measurements must be performed within one week (Day -7 to Day 1) before the patient goes in the trial.
• Female patients with child-bearing potential must have a negative urine or serum pregnancy test within 7 days prior to start of trial.
• Women/females of child bearing potential or their male partners must use a highly effective method of contraception for 2 weeks before starting the study treatment, throughout the treatment period and for 1 month after discontinuation of treatment with palbociclib and avelumab (women/female patients) or 14 weeks (men/male patients). Highly effective methods are defined as methods that can achieve a failure rate of less than 1% per year when used consistently and correctly are considered as highly effective birth control methods, such methods include:
⁃ Oral, intra-vaginal or transdermal combined hormonal contraception
⁃ Oral, injectable or implantable progesterone-only contraception
⁃ Intrauterine device
⁃ Intrauterine hormone-releasing system,
⁃ Bilateral tubal occlusion
⁃ Vasectomised partner
⁃ True abstinence:\* When this is in line with the preferred and usual lifestyle of the subject
• Key: \* it is only considered highly effective if the patient is refraining from sexual intercourse during the entire period of risk associated with the study treatments
• Age 18 years of age or over
• World Health Organisation (WHO) performance status 0 or 1
• Estimated life expectancy of at least 3 months in the opinion of the investigator
• Signed and dated informed consent
⁃ Patients willing and able to comply with scheduled visits, treatment plans, laboratory tests, follow up, and other procedures
⁃ Available archival breast primary tumour tissue (or metastatic tissue if de novo metastatic disease)
⁃ Patient willing to undergo a mandatory baseline fresh tumour tissue biopsy procedure (clinical or radiologically-guided)