An open-label, two-stage Phase I/IIa dose escalation study of BT062 in metastatic triple receptor-negative breast cancer and in metastatic transitional cell carcinoma of the urinary bladder

Phase 1

• Conditions: Subjects with metastatic triple receptor-negative breast cancer (TNBC) who failed at least 2 and no more than 4 prior chemotherapies or alternativelySubjects with metastatic transitional cell carcinoma (TCC) of the urinary bladder who failed at least 1 and no more than 2 prior chemotherapies.; MedDRA version: 19.0Level: PTClassification code 10071664Term: Bladder transitional cell carcinoma metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 19.0Level: PTClassification code 10055113Term: Breast cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2013-003252-20-DE
• Lead Sponsor: Biotest AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-09-13
• Last Update Posted: 2 October 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 180

Inclusion Criteria

1. Signed written Informed Consent Form in accordance with institutional guidelines and applicable national law, prior to any study-related procedure;
2. Diagnosis:
• metastatic triple-negative breast cancer with histochemical confirmation of the absence of progesterone receptors, estrogen receptors and human epidermal growth factor receptors
or
• metastatic transitional celll carcinoma of the urinary bladder
3. Relapsed or relapsed / refractory disease at a stage that cannot be controlled adequately by surgery, radiotherapy or standard chemotherapy;
3a: Patients presenting with triple negative breast cancer and who failed at least 2, but not more than 4 previous chemotherapy / drug therapy regimens. In patients who failed more than 2 prior chemotherapy / drug therapy regimens, the last progression of disease must not have been observed earlier than within 9 weeks of the start of the treatment.
3b: Patients presenting with urinary bladder cancer and who failed at least 1, but not more than 2 previous chemotherapy regimens.
4. Measurable disease according to the RECIST (v1.1) with at least one measurable lesion and at least one tumor biopsy with histologically confirmed malignancy;
5. Histological confirmation of moderate to high CD138 expression for at least one lesion;
6. Female or male patients aged > 18 years;
7. Estimated life expectancy = 12 weeks;
8. Eastern Cooperative Oncology Group (ECOG) Performance Status = 2;
9. Absolute neutrophil count (ANC) = 1500 cells / µL;
10. Hemoglobin (Hb) = 9.0 g / dL;
11. Platelet count = 100,000 / µL at screening;
12. Liver transaminases:
• In patients without liver metastases: AST (SGOT) and ALT (SGPT) = 3 times the upper limit of normal (ULN);
• In patients with liver metastases: AST (SGOT) and ALT (SGPT) = 5 times the ULN, provided that there is no evidence of other reasons for transaminase level increase,
13. Total bilirubin = 1.5 times the ULN;
14. Lipase = 3 times the ULN;
15. Renal function:
Serum creatinine = 2 mg / dL; Creatinine clearance (CRCL) = 50 mL / min;
16. Ability to understand, and willingness to sign a written Informed Consent Form;
17. Ability and willingness to adhere to the study visit schedule and all protocol procedures;
18. Subjects must use two acceptable methods of birth control from the point of signing Informed Consent Form (ICF) until 3 months after administration of the last dose of study drug;
19. Patients must agree not to donate blood from the point of signing the ICF until at least 1 month after administration of the last dose of the study drug;
20. Negative serum or urine pregnancy test in female patients of childbearing potential.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 60

Exclusion Criteria

1. History of allergy against study drug related components or drugs
2. Administration of chemotherapy or radiotherapy within 3 weeks prior to day of first dose of study drug or during the study;
3. Chemotherapy with nitrosoureas or mitomycin C within 6 weeks prior to day 1
4. Antineoplastic therapy with biological agents within 2 weeks before day 1 or within 5 drug half-lifes (t½) prior to first dose, whichever time period is longer
5. Participation in an investigational therapeutic study within 3 weeks or within 5 drug half-lives (t1/2) prior to first dose, whichever time is longer.
6. Treatment with BT062 in previous studies;
7. Previous treatment with vinflunine;
8. Planned tumor-reduction surgery and surgical removal of well accessible metastases;
9. Anticipation of the need to apply radiotherapy during the first 3 cycles/12 weeks of the study.
10. Major surgery within 4 weeks prior to Day 1;
11. Persistence of clinically relevant symptoms of incomplete recovery from a previous major surgery;
12. Malignancy (other than the trial indications) within the past three years except:
• Treated non-melanoma skin cancer;
• Carcinoma in-situ of the cervix uteri;
• Prostate carcinoma (Gleason Grade = 6) with stable prostate specific antigen (PSA) levels
13. Active metastasis of the central nervous System
14. In patients of the dose escalation part (first part) of the study: treatment with denosumab within 5 months before the first dose of BT062 and/or planned treatment with denosumab any time during the treatment with BT062.
15. In patients in the phase II part of the study who are scheduled to continue an ongoing denosumab treatment as a concomitant medication during the BT062 regimen:
a)treatment with denosumab that started less than 6 months before
the first dose of BT062
b)changes in the denosumab dose level of more than 33% in the
monthly dose in the last 3 months.
c)history of severe hypercalcemia or hypocalcemia (of any origin)
d)history of severe hypokalemia or severe hyperkalemia (of any origin)
e)history of osteonecrosis (of any origin)
f)history of severe adverse reactions that were assessed as
related to denosumab
g)history of severe pain that was assessed as related to denosumab
h)history of hypersensitivity reactions to denosumab or any of its
excipients

16. Severe inflammatory diseases of skin, colon, esophagus, stomach, small intestine, or eye within 1 year prior to first dose;
17. Acute active infection requiring systemic antibiotics, antivirals, or anti-fungals within 28 days prior to first dose;
18. Known or suspected HIV infection, known HIV seropositivity, or active hepatitis A, B, or C infection, active tuberculosis or any other concurrent disease which disqualifies the patient for enrollment
19. Acute or clinically relevant abnormalities in electrocardiogram (ECG);
20. Significant cardiac disease(= 6 months prior to Day 1)
21. Uncontrolled hypertension (recurrent or persistent increases in systolic blood pressure = 180 mm Hg or diastolic blood pressure = 110 mm Hg),
22. History of clinically significant drug or alcohol abuse or ongoing clinically significant alcohol or drug abuse;
23. Unwillingness or inability to adhere to the requirements of the study;
24. Serious psychiatric or any other medical condition (including laboratory abnormalities), that could interfere with treatment and puts the patient at an unacceptable risk;
25. Subject is a pregnant or nursing woman or

Study & Design

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