Study investigating safety and efficacy of PQR309 and eribulin combination in patients with locally advanced or metastatic HER2 negative and triple-negative breast cancer

Phase 1

• Conditions: ocally advanced or metastatic HER2 negative and triple-negative breast cancer; MedDRA version: 19.0 Level: LLT Classification code 10027475 Term: Metastatic breast cancer System Organ Class: 100000004864; MedDRA version: 19.0 Level: LLT Classification code 10072740 Term: Locally advanced breast cancer System Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2015-004225-14-GB
• Lead Sponsor: PIQUR Therapeutics AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2015-11-23
• Last Update Posted: 28 February 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 31

Inclusion Criteria

1. Female = 18 years old at the time of informed consent.
2. Histologically/cytologically confirmed diagnosis of breast cancer.
3. Radiological evidence of inoperable locally advanced or metastatic breast cancer.
4. HER2 negative breast cancer (based on the most recent analyzed biopsy) defined as a negative in situ hybridization test (ISH) or an immunohistochemistry (IHC) status of 0, 1+ or 2+ (if IHC 2+, a negative in situ hybridization test is required) by local laboratory testing.
5. Estrogen receptor and progesterone receptor status known as per local laboratory testing.
6. Received at least 2 and no more than 5 prior chemotherapeutic regimens in locally advanced and/or metastatic setting. Prior therapy has to include an anthracycline and a taxane in any combination or order (unless contraindicated for a certain patient). Prior anti-hormonal therapy is allowed.
7. Stable Eastern Cooperative Oncology Group (ECOG) performance status = 2.
8. More than 4 weeks from any investigational agent.
9. Adequate bone marrow and organ function as defined by the following laboratory values:
- Absolute neutrophil count (ANC) = 1.5x10^9/l, platelets = 100x10^9/l, hemoglobin = 100g/L.
- Potassium, phosphate, calcium (corrected for serum albumin) and magnesium within normal limits (WNL) for the institution.
- Total bilirubin = 1.5 times the upper limit of normal (ULN).
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 2.5 times ULN.
- Fasting plasma glucose = 125 mg/dL (= 7 mmol/L).
10. Able and willing to swallow and retain oral medication.
11. Written informed consent obtained according to local guidelines.
Expansion part:
12. Triple-negative breast cancer (based on most recently analyzed biopsy) defined as a negative in situ hybridization test or an IHC status of 0, 1+ or 2+ (if IHC 2+, a negative in situ hybridization is required), ER and PR status < 10% (equivalent to Allred score of 2 or less) by local laboratory testing.
13. Measurable disease according to RECIST v.1.1 or non-measurable lytic or mixed (lytic + blastic) bone lesions with an identifiable soft tissue component that meets the measurability criteria per RECIST v.1.1
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 31
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 31

Exclusion Criteria

1. Previous systemic treatment with PI3K, mTOR or AKT inhibitors (allowed in the escalation part).
2. Previous treatment with eribulin (allowed in the escalation part).
3. Known hypersensitivity to any of the excipients of PQR309 or eribulin.
4. Concurrent treatment with other approved or investigational antineoplastic agent.
5. Symptomatic CNS metastases. The patient must have completed any prior local treatment for CNS metastases = 28 days prior to first dose of the study drug (including radiotherapy and/or surgery).
6. Clinically manifested diabetes mellitus (treated and/or clinical signs with fasting glucose > 125 mg/dl), or documented steroid induced diabetes mellitus.
7. Peripheral neuropathy = CTC AE grade 2.
8. Anxiety = CTC AE grade 3.
9. Concurrent malignancy other than HER2 negative BC or malignancy within 3 years of study enrollment (with the exception of adequately treated, basal or squamous cell carcinoma, non-melanomatous skin cancer or curatively resected cervical cancer).
10. Received radiotherapy = 3 weeks or limited field radiation for palliation = 2 weeks prior to starting study drug, and not recovered or improved to grade 1 from related side effects of such therapy (exceptions include alopecia) and/or from whom = 30% of the bone marrow was irradiated.
11. Not recovered or improved to grade 1 from related side effects (except alopecia) of any prior antineoplastic therapy.
12. Major surgery within 14 days prior to first dose of the study drug or not recovered from major side effects.
13. Received systemically high doses of corticosteroids = 2 weeks prior to starting study drug, or not fully recovered from side effects of such treatment.
Stable doses of corticosteroids, no more than 1 mg of dexamethasone a day or equivalent, e.g. 6 mg prednisone or 25 mg hydrocortisone for at least 5 days prior to first dose of the study drug is allowed.
14. Currently receiving warfarin or other coumarin derived anti-coagulant, for treatment, prophylaxis or otherwise. Therapy with heparin, low molecular weight heparin (LMWH), or fondaparinux is allowed.
15. Treatment with medicinal products that increase the pH (reduce acidity) of the upper Gastro-Intestinal (GI) tract, including, but not limited to: protonpump inhibitors (e.g. omeprazole), H2-antagonists (e.g. ranitidine) and antacids. Patients may be enrolled in the study after a wash out period sufficient to terminate their effect.
16. Using herbal preparations or medications within = 7 days prior to first dose of the study drug.
17. Any severe or uncontrolled cardiac disease or history of cardiac dysfunction (Section 9.3 of protocol).
18. Left Ventricular Ejection Fraction (LVEF) < 50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO).
19. Cardiac conduction abnormalities (Section 9.3 of protocol).
20. QTcF > 480 msec on the screening ECG (using the QTcF formula).
21. Currently receiving treatment with medication that has a known risk to prolong the QT interval or inducing Torsades de Pointes, and the treatment cannot be discontinued or switched to a different medication prior to rand

Study & Design

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