A study of copanlisib in combination with trastuzumab for treatment of women with HER2 positive advanced breast cancer.
- Conditions
- HER2 positive metastatic or recurrent breast cancer, following disease progression during, or after, treatment with at least one treatment regimen in the metastatic or recurrent setting.MedDRA version: 20.0Level: LLTClassification code 10027475Term: Metastatic breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: PTClassification code 10006198Term: Breast cancer recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2015-003687-36-IE
- Lead Sponsor
- Cancer Trials Ireland CLG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Female
- Target Recruitment
- 31
1. Adult women = 18 years of age with histologically confirmed, recurrent, or metastatic, HER2-positive breast cancer.
2. Histologically confirmed HER2-positive breast cancer:
o Documented HER2 overexpression by local laboratory (IHC 3+ or FISH or CISH positive).
o IHC 3+ or FISH/CISH positive on diagnostic breast biopsy or surgical breast resection sample or metastatic disease site biopsy.
3. Recurrent incurable or metastatic breast cancer.
4. Eligible recurrent disease is recurrent disease that is considered incurable by the treating oncologist. Many local-only recurrences are treated with curative intent; a treatment plan with curative intent for a local-only recurrence would indicate that the patient is not eligible for this clinical trial. A local-only recurrence must be considered incurable by the treating oncologist for the patient to be eligible. A t least one measurable lesion according to RECIST criteria (Version 1.1). Patients with bone only disease are not eligible.
5. Patient has received at least one trastuzumab-based or TDM1-based treatment regimen in the setting of metastatic disease or incurable locoregional recurrence. A trastuzumab-based or TDM1-based treatment regimen is considered as any treatment regimen that includes trastuzumab or TDM1.
- Patients must have had at least 1 line of therapy for metastatic and/or incurable locoregional recurrent disease to be eligible. A patient is eligible regardless of the period of time from adjuvant therapy so long as she has disease that is progressing after at least 1 line of trastuzumab-based therapy in the setting of metastatic disease and/or incurable locoregional recurrence.
6. Disease progression during or following at least 1 prior trastuzumab-based or trastuzumab emtansine (T-DM1) based treatment regimen in the setting of metastatic disease or incurable locoregional recurrence.
7. ECOG performance status = 2.
8. Life expectancy of at least 3 months.
9. Availability of fresh tissue and/or archival tumour tissue at screening.
10. Women of childbearing potential must agree to use a highly effective method of contraception when sexually active. This applies from signing of the informed consent form until at least 100 days after the last study drug administration. Please refer to protocol for full details.
11. Adequate baseline laboratory values collected no more than 14 days before starting study treatment:
- Total bilirubin = 1.5 x ULN (< 3 x ULN for patients with metastatic disease in the liver).
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =3.0 x ULN (= 5 x ULN for patients with liver involvement from breast cancer).
- Glomerular filtration rate (GFR) = 30 mL/min/1.73 m2 according to the Modification of Diet in Renal Disease (MDRD) abbreviated formula. If not on target, this evaluation may be repeated once after at least 24 hours either according to the MDRD abbreviated formula or by 24 hour sampling. If the later result is within acceptable range, it may be used to fulfil the inclusion criteria instead.
- International normalized ratio (INR) and partial thromboplastin time (PTT) = 1.5 x ULN. Patients who are therapeutically treated with an agent such as warfarin or heparin will be allowed to participate provided that no prior underlying coagulopathy disorder. Close monitoring of these patients (Day 15 of Cycle 1 and Day 1 of each cycle) will be performed until INR/PTT is stable based on a measurement that is pre-dose as defined by th
1. Known breast cancer involvement of the brain, unless adequately controlled based on the clinical judgement of the treating physician.
2. Congestive heart failure > New York Heart Association (NYHA) class II.
3. Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months). Myocardial infarction less than 6 months before registration.
4. Uncontrolled arterial hypertension despite optimal medical management (per investigator’s opinion).
5. Uncontrolled Type I or II diabetes mellitus. Defined as HbA1c > 8.5% as determined during screening laboratory assessments.
6. Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 3 months before registration.
7. Non-healing wound, ulcer, or bone fracture.
8. Active, clinically serious infections > CTCAE Grade 2 (CTCAE v4.0).
9. Known history of human immunodeficiency virus (HIV) infection.
10. Hepatitis B (HBV) or hepatitis C (HCV). All patients must be screened for HBV and HCV up to 28 days prior to study drug start using the routine hepatitis virus laboratory panel (HBsAg, HBsAb,…). Patients who test positive for HBsAg or HBcAb will be eligible if they are negative for HBV-DNA; patients who test positive for anti-HCV antibody will be eligible if they are negative for HCV-RNA.
11. Patients with CMV PCR positive.
12. Patients with seizure disorder requiring medication.
13. Patients with evidence or history of bleeding diathesis. Any haemorrhage or bleeding event = CTCAE Grade 3 within 4 weeks prior to the start of study treatment.
14. Proteinuria of Grade 3 or higher (CTCAE v4.0). Patient will be excluded if > 2+ on urinalysis (unless 24 hr collection shows 24 hour urinary protein < 3.5g/24hrs).
15. History or concurrent condition of interstitial lung disease of any severity, and/or severely impaired lung function (as judged by the investigator).
16. Concurrent diagnosis of pheochromocytoma.
17. Pregnant or breast-feeding patients. Women of childbearing potential must have a serum or urine pregnancy test performed a maximum of 7 days before start of treatment, and a negative result must be documented before start of treatment.
18. Unresolved toxicity higher than CTCAE Grade 1 attributed to any prior therapy/procedure, excluding alopecia, peripheral neuropathy, and bone marrow parameters.
19. Known hypersensitivity to any of the test drugs, test drug classes, or excipients in the formulation.
20. Substance abuse, medical, psychological or social conditions that may interfere with the patient’s participation in the study or evaluation of the study results.
21. Any illness or medical conditions that are unstable or could jeopardize the safety of patients and their compliance in the study.
22. Patients permanently withdrawn from study participation will not be allowed to re-enter the study.
Excluded previous therapies and medications:
23. Treatment with investigational drugs other than PI3K inhibitors less than 28 days before start of treatment.
24. Ongoing immunosuppressive therapy.
25. Radiotherapy of a target lesion or immuno-/chemotherapy less than 4 weeks (28 days) before start of treatment.
26. Myeloid growth factors less than 7 days before start of treatment.
27. Blood or platelet transfusion less than 7 days before start of treatment.
28. Ongoing systemic corticosteroid therapy at a daily dose higher than 15 mg prednis
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method