An open-label, early stage, dose rising study of 2B3-101 in patients with solid tumors and brain metastases or recurrent malignant glioma.

• Conditions: Therapeutic area: Diseases [C] - Cancer [C04]; Solid tumors and brain metastases or recurrent malignant glioma, HER2-positive adenocarcinoma of the breast with brain metastases,; MedDRA version: 17.0Level: PTClassification code 10065443Term: Malignant gliomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 17.0Level: LLTClassification code 10027475Term: Metastatic breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 17.0Level: LLTClassification code 10006128Term: Brain metastasesSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 17.0Level: PTClassification code 10059514Term: Small cell lung cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

• Registration Number: EUCTR2011-001119-30-BE
• Lead Sponsor: to-BBB technologies B.V.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-12-13
• Last Update Posted: 17 August 2015

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 129

Inclusion Criteria

1. Age = 18 years.
2. Measurable intracranial disease by MRI.
3. ECOG Performance Status = 2.
4. Estimated life expectancy of at least 8 weeks.
5. Toxicities incurred as a result of previous anticancer therapy (radiation therapy, chemotherapy, or surgery) must be resolved to = grade 2 (as defined by CTCAE version 4.0).
6. No evidence of (cortical) cognitive impairment as defined by a Mini-Mental Status Exam (MMSE) score = 25/30.
7. Written informed consent according to local guidelines.
8.
2B3-101 single agent dose-escalation phase:
na

2B3-101 in combination with trastuzumab dose-escalation phase:
na

Breast cancer brain metastases study- arm of the expansion phase:
Patients with pathologically confirmed diagnosis of advanced, recurrent breast cancer with unequivocal evidence of brain metastases that are refractory to standard therapy or for whom no standard therapy exist.
OR
Patients with pathologically confirmed diagnosis of advanced breast cancer with newly diagnosed, untreated, brain metastases, which per multi-disciplinary team decision do not require immediate radiotherapy or surgery.

Patients with histologically-confirmed HER2-positive adenocarcinoma of the breast with unequivocal evidence of brain metastases that are refractory to standard therapy or for which no standard therapy exist or with unequivocal evidence of newly diagnosed untreated brain metastases, which per the multi-disciplinary team decision do not require immediate radiotherapy or surgery

SCLC brain metastases study arm of the expansion phase:
Patients with pathologically confirmed diagnosis of advanced, recurrent SCLC with unequivocal evidence of brain metastases that are refractory to standard therapy or for whom no standard therapy exist.
OR
Patients with pathologically confirmed diagnosis of advanced SCLC with newly diagnosed, untreated, brain metastases, which per multi-disciplinary team decision do not require immediate radiotherapy or surgery.

Melanoma brain metastases study arm of the expansion phase:
Patients with pathologically confirmed diagnosis of advanced, recurrent melanoma with unequivocal evidence of brain metastases that are refractory to standard therapy or for whom no standard therapy exist.
OR
Patients with pathologically confirmed diagnosis of advanced mel;anoma with newly diagnosed, untreated, brain metastases, which per multi-disciplinary team decision do not require immediate radiotherapy or surgery.

Recurrent malignant glioma study- arm of the expansion phase:
7 patients with histologically proven glioma grade IV, which is progressive following first line treatment with surgery or biopsy followed by fractionated radiotherapy with concurrent temozolomide-containing chemotherapy.
7 patients with histologically confirmed recurrent malignant (WHO grade III and IV) glioma or histologically confirmed low-grade (WHO grade II) glioma with radiographic evidence of malignant transformation by MRI, that are refractory to standard therapy, or for whom no standard therapy exists or do not require immediate standard therapy per the multi-disciplinary team decision.

Breast cancer brain metastases extension cohort of the expansion phase arm
See expansion phase

SCLC brain metastases extension cohort of the expansion phase arm
See expansion phase

Recurrent glioma extension cohort of the expansion phase arm
See expansion phase

Are the trial subjects under 18? no
Number of subjects for t

Exclusion Criteria

Prior Treatment:
1. Less than 1 week since the last treatment of lapatinib, dabrafenib, everolimus, capecitabine, anastrazole, letrozole and exemestane, less than 2 weeks since the last treatment of vemurafenib; less than 4 weeks since the last treatment of trametinib, chemotherapy, biological therapy, immunotherapy and systemic radiotherapy (except palliative radiation delivered to <20% of bone marrow), less than 6 weeks for nitrosoureas and mitomycin C and less than 8 weeks for cranial radiotherapy. Previous trastuzumab treatment will be allowed to continue without interruption in patients that are included in either the 2B3-101 dose-escalation phase in combination with trastuzumab or in the breast cancer expansion phase once the MTD for the combination has been established.
2. Patients that have received a maximum cumulative dose of free (i.e., non-liposomal) or liposomal doxorubicin > 360mg/m2 or free epirubicin > 600mg/m2
Current Treatment:
3. Current or recent (within 30 days of first study treatment) treatment with another investigational drug or participation in another investigational study.

Hematology, coagulation and biochemistry:
4. Inadequate bone marrow function: Absolute Neutrophil Count (ANC): < 1.5 x 109/L, or platelet count < 100 x 109/L or hemoglobin < 6 mmol/L.
5. Inadequate liver function, defined as:
• Serum (total) bilirubin > 1.5 x the Upper Limit of Normal (ULN) for the institution if no liver metastases (> 2 x ULN in patients with liver metastases);
• Aspartate Amino Transferase (ASAT) or Alanine Amino Transferase (ALAT) > 2.5 x ULN if no liver metastases (> 4x ULN in patients with liver metastases);
• Alkaline phosphatase levels > 2.5 x ULN if no liver metastases (> 5 x ULN in patients with liver metastases, or > 10 x ULN in patients with bone metastases).
6. Inadequate renal function, defined as:
• Serum creatinine > 1.5 x ULN.
Other:
7. Leptomeningeal carcinomatosis as the only site of CNS involvement.
8. Pregnancy or lactation. Serum pregnancy test to be performed in female subjects of childbearing potential (defined as < 2 years after last menstruation and not surgically sterile) within 7 days prior to study treatment start, or within 14 days followed by a confirmatory urine pregnancy test within 7 days prior to study treatment start.
9. For female subjects of childbearing potential (defined as < 2 years after last menstruation and not surgically sterile) and male subjects who are not surgically sterile or with partners of childbearing potential: absence of effective, non-hormonal means of contraception (intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal gel).
10. Major surgical procedure (including open biopsy, excluding central line IV and portacath) within 28 days prior to the first study treatment, or anticipation of the need for major surgery during the course of the study treatment.
11. Grade 3 or 4 motor, sensory, or cranial neuropathy symptoms (as defined by CTCAE version 4.0).
12. Uncontrolled hypertension (systolic > 150 mm Hg and/or diastolic >100mm Hg).
13. Clinically significant (i.e. active) cardiovascular disease defined as:
• Stroke within = 6 months prior to day 1;
• Transient Ischaemic Attack (TIA) within = 6 months prior to day 1;
• Myocardial infarction within = 6 months prior to day 1;
• Unstable angina;
• New York Heart Association (NYHA) Grade II or greater Congestive Heart Failure (CHF);
• Serio

Study & Design

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