BI 860585 Dose Escalation Single Agent and in Combination With Exemestane or With Paclitaxel in Patients With Various Advanced and/or Metastatic Solid Tumors

Boehringer Ingelheim

Status and phase: Completed; Phase 1

Conditions: Neoplasms

Treatments: Drug: paclitaxel; Drug: exemestane; Drug: BI 860585

Study type: Interventional

Funder types: Industry

Identifiers

NCT01938846

1325.1

2013-000765-36 (EudraCT Number)

Details and patient eligibility

About

The primary objective of the trial is to determine the maximum tolerated doses (MTD) of BI 860585 alone and in combination with exemestane or paclitaxel. To determine the MTDs, patients are entered sequentially into escalating dose cohorts. Secondary objectives are objective response and disease control according to RECIST criteria version 1.1

Enrollment: 90 patients

Sex: All

Ages: 18 to 99 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients with histologically or cytologically confirmed diagnosis of advanced, measurable or evaluable, non-resectable and/or metastatic solid tumours, which has shown to be progressive;
• Patients who have received previous standard of care therapy for their disease and have progressed;
• 18 years or older;
• Life expectancy >= 3 months;
• Written informed consent in accordance with International Conference on Harmonisation/Good Clinical Practice (ICH/GCP) and local legislation;
• Eastern Cooperative Oncology Group (ECOG), performance score 0-2.

Additional inclusion criteria for the combination arms:

• Patients must have confirmed progressive disease within the last 6 months, (in case of measurable disease, progression should be confirmed according to Response Evaluation Criteria in Solid Tumours (RECIST) criteria version 1.1;
• Patients carrying a tumour for whom treatment with either exemestane or paclitaxel would be considered appropriate by the investigator;

Additional inclusion criteria for expansion part:

• Patients must have measurable progressive disease within the last 6 months documented/proven according to RECIST criteria version 1.1.
• Patients entering the expansion cohorts must also have:
• Arm A: any advanced/metastatic solid tumour suitable for biopsy and must have provided informed consent for biopsy and biomarker analysis.
• Arm B: any cytologically or histologically confirmed ER+ (estrogen receptor positive) advanced/metastatic solid tumours for which treatment with exemestane would be considered appropriate by the investigator.
• Arm C: any advanced/metastatic solid tumour for which treatment with paclitaxel would be considered appropriate by the investigator.

Exclusion criteria

• Serious concomitant non-oncological disease/illness considered by the investigator to be incompatible with the protocol;
• Patients with untreated or symptomatic brain metastases;
• Second malignancies requiring active therapy;
• Clinical Congestive Heart Failure (CHF) Grade III-IV;
• Myocardial infarction within the last 6 months prior to inclusion, or symptomatic coronary artery disease;
• Adequate bone marrow, liver and renal function;
• Patients with known HIV/hepatitis/active infectious disease considered by the investigator to be incompatible with the protocol;
• Patients unable to take oral medication;
• Chronic diarrhoea or other gastrointestinal disorders;
• Treatment with anti-cancer-therapies: cytotoxic or standard chemotherapy, immunotherapy, radiotherapy, biological therapies, molecular targeted or other investigational drugs, within four weeks of the first treatment with the study medication (or within one week for non-cytotoxic drugs);
• Recovery from previous surgery and anticancer medical treatments;
• Hypersensitivity to combination drugs or excipients;
• Patients with a history of uncontrolled diabetes mellitus.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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90 participants in 3 patient groups

BI 860585

Experimental group

Description:

Multiple ascending doses of BI 860585 administered continuously in a 28-day cycle, including food interaction cohorts

Treatment:

Drug: BI 860585

Drug: BI 860585

Drug: BI 860585

BI 860585 + paclitaxel

Experimental group

Description:

Multiple ascending doses of BI 860585 in combination with fixed dose paclitaxel

Treatment:

Drug: paclitaxel

Drug: BI 860585

Drug: BI 860585

Drug: BI 860585

BI 860585 + exemestane

Experimental group

Description:

Multiple ascending doses of BI 860585 in combination with fixed dose exemestane

Treatment:

Drug: exemestane

Drug: BI 860585

Drug: BI 860585

Drug: BI 860585