Overview

PAveMenT: Palbociclib and Avelumab in Metastatic AR+ Triple Negative Breast Cancer

Status:
Recruiting
Trial end date:
2024-07-01
Target enrollment:
0
Participant gender:
All
Summary
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.
Phase:
Phase 1
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Royal Marsden NHS Foundation Trust
Collaborators:
Breast Cancer Now
Pfizer
Treatments:
Avelumab
Palbociclib
Criteria
Inclusion Criteria Part A:

1. Patients with recurrent inoperable locally advanced or metastatic breast cancer.

2. 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.

3. Measurable disease (RECIST 1.1)

4. 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.

5. 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

6. 18 years of age or over.

7. World Health Organisation (WHO) performance status 0 or 1

8. Estimated life expectancy of at least 3 months in the opinion of the investigator

9. Signed and dated informed consent.

10. Patients willing and able to comply with scheduled visits, treatment plans, laboratory
tests, follow up and other procedures

Inclusion Criteria Part B:

1. 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.

2. 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.

3. Measurable disease (RECIST 1.1) amenable to fresh biopsy

4. 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.

5. 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

6. Age 18 years of age or over

7. World Health Organisation (WHO) performance status 0 or 1

8. Estimated life expectancy of at least 3 months in the opinion of the investigator

9. Signed and dated informed consent

10. Patients willing and able to comply with scheduled visits, treatment plans, laboratory
tests, follow up, and other procedures

11. Available archival breast primary tumour tissue (or metastatic tissue if de novo
metastatic disease)

12. Patient willing to undergo a mandatory baseline fresh tumour tissue biopsy procedure
(clinical or radiologically-guided)

Exclusion Criteria Parts A & B:

1. Systemic chemotherapy or investigational medicinal products during the previous four
weeks, or hormonal therapy within 7 days except luteinizing hormone-releasing hormone
(LHRH) analogues for ovarian suppression. Bisphosphonates or RANK ligand antagonists
are permitted for the management of bone metastases.

2. Previous exposure to immune checkpoint inhibitors or immune co-stimulatory drugs.

3. Previous treatment with palbociclib or any agents which inhibit CDK4/6

4. Major surgery (excluding minor procedures, e.g. placement of vascular access) within 4
weeks or radiation therapy within 14 days prior to study entry

5. Patients with known symptomatic brain metastases requiring steroids, untreated brain
metastases, leptomeningeal disease or spinal cord compression.

6. Active infection requiring systemic therapy

7. Any of the following within 12 months prior to study entry: myocardial infarction,
history of myocarditis, uncontrolled angina, coronary/peripheral artery bypass graft,
symptomatic congestive heart failure, cerebrovascular accident, or transient ischemic
attack.

8. Uncontrolled hypertension or cardiac dysrhythmia including atrial fibrillation

9. Active autoimmune disease that might deteriorate when receiving an immuno-stimulatory
agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid
diseases not requiring immunosuppressive treatment are eligible.

10. Current use of immunosuppressive medication, EXCEPT for the following: a. intranasal,
inhaled, topical steroids, or local steroid injection (e.g., intra-articular
injection); b. Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone
or equivalent; c. Steroids as premedication for hypersensitivity reactions (e.g., CT
scan premedication).

11. Other severe acute or chronic medical conditions including colitis, inflammatory bowel
disease, pneumonitis (even if fully resolved), pulmonary fibrosis, end stage renal
disease on haemodialysis or psychiatric conditions including recent (within the past
year) or active suicidal ideation or behaviour; or laboratory abnormalities that may
increase the risk associated with study participation or study treatment
administration or may interfere with the interpretation of study results and, in the
judgment of the investigator, would make the patient inappropriate for entry into this
study.

12. Patients on warfarin. Patients requiring anticoagulation for rate-controlled AF or
previous venous thromboembolism should be switched to low-molecular weight heparin.

13. Known HIV or AIDS-related illness, active infection requiring systemic therapy, or
positive HBV or HCV test indicating acute or chronic infection

14. Known severe hypersensitivity reactions to monoclonal antibodies (Grade ≥ 3 NCI CTCAE
v 5), any history of anaphylaxis, or uncontrolled asthma (that is, 3 or more features
of partially controlled asthma)

15. Inability or unwillingness to swallow pills, or receive IV injections.

16. Persisting toxicity related to prior therapy >Grade 1 (except for stable peripheral
neuropathy grade ≤2 or alopecia grade ≤2).

17. Pregnancy or lactation (women/females of childbearing potential must have a negative
pregnancy test within 7 days prior to treatment initiation)

18. Diagnosis of other malignancy within 3 years, except for adequately treated basal cell
or squamous cell skin cancer, or carcinoma in situ of the breast or cervix, or
low-grade (Gleason ≤6) prostate cancer

19. Is a participant or plans to participate in another interventional clinical trial,
whilst taking part in this study. Participation in an observational trial would be
acceptable.

20. Known prior or suspected hypersensitivity to investigational products or to any of the
excipients

21. Vaccination within 4 weeks of the first dose of avelumab and while on trial is
prohibited except for administration of inactivated vaccines. Live vaccines must also
be avoided for 3 months after the last dose of avelumab.

22. Any psychiatric condition that would prohibit the understanding or rendering of
informed consent

23. Requirement for continued use of preparations containing St. John's Wort is
specifically contraindicated. Other herbal medicinal or natural products that patient
is intended to take during the trial must be explored at the beginning and during the
course of the trial and discussed with the investigator.

24. Requirement for continued use of CYP3A inhibitors, inducers or substrates (listed in
Appendix 4).

25. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase
deficiency, or glucose-galactose malabsorption should not take this medicine as this
medicinal product contains lactose.

26. Any other condition which in the Investigator's opinion would not make the patient a
good candidate for the clinical trial.