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

• Conditions: Solid tumors and brain metastases or recurrent malignant glioma, HER2-positive adenocarcinoma of the breast with brain metastases; MedDRA version: 14.1Level: LLTClassification code 10065147Term: Malignant solid tumorSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 14.1Level: LLTClassification code 10065252Term: Solid tumorSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 14.1Level: PTClassification code 10065443Term: Malignant gliomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 14.1Level: LLTClassification code 10027475Term: Metastatic breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 14.1Level: LLTClassification code 10006128Term: Brain metastasesSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

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

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-04-12
• Last Update Posted: 1 December 2014

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 82

Inclusion Criteria

To be eligible to participate in this study, candidates must meet the following eligibility 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.

In addition to the above listed eligibility criteria, the following criteria are applicable:
8.2B3-101 single agent dose-escalation phase:
Patients with pathologically confirmed diagnosis of advanced, recurrent solid tumors and unequivocal evidence of brain metastases that are refractory to standard therapy or for whom no standard therapy exists or with unequivocal evidence of newly diagnosed untreated brain metastases and controlled extracranial disease.

OR

Patients with pathology confirmed diagnosis of advanced, recurrent primary malignant (grade III and IV) glioma that are refractory to standard therapy or for whom no standard therapy exists.

2B3-101 in combination with trastuzumab dose-escalation phase:
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 and controlled extracranial disease.

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

Exclusion Criteria

Candidates will be excluded from study entry if any of the following exclusion criteria exist:

Prior Treatment:
1.Less than 1 week since the last treatment of lapatinib, less than 2 weeks since the last treatment of vemurafenib, less than 4 weeks since the last treatment of chemotherapy, biological therapy, immunotherapy and systemicradiotherapy (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 ULN for the institution if no liver metastases (> 2 x ULN in patients with liver metastases);
•ASAT or ALAT > 2.5 x ULN if no liver metastases (> 4 x 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 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 female 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 Ischemic 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);
•Serious cardiac arrhythmia requiring medication;
•Clinically relevant pathologic findings in ECG.
14.14.Left Ventricle Ejection Fraction (LVEF) by MUGA or ECHO < 55% for patients recei

Study & Design

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