A Phase I, Dose Escalation Study of BNC101 in Patients With Metastatic Colorectal Cancer.

NCT02726334 | Terminated Phase 1 DMC

• 1 other identifier: BNC101. 001
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 4

Brief Summary

The purpose of this study is to determine the maximum tolerated dose (which will be the dose recommended for a Phase 2 study), safety, tolerability and pharmacokinetic profile (study of movement of the drug within the body, including absorption and distribution) of the study drug, BNC101 when administered intravenously as a single agent or in combination with chemotherapy in patients with metastatic colorectal cancer who have failed at least 1 or 2 lines of chemotherapy.

Conditions

Colorectal Cancer

Keywords

Metastatic

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose

  To determine the maximum tolerated dose (MTD) of BNC101, both as single agent and in combination chemotherapy in metastatic colorectal cancer patients.

  DLT period of 28 days per dose level

Study Arms (2)

Group/Stream 1 - Monotherapy

EXPERIMENTAL

Patient group: Patients who have failed at least two lines of chemotherapy for metastatic disease. Treatment: BNC101 administered via intravenous infusion over 60 minutes weekly. Patients with stable disease or a response at or after day 56 (2 cycles) will be allowed to continue to receive weekly doses of BNC101 until disease progression.

Drug: BNC101 Solution for Infusion

Group/Stream 2 - Combination Chemo

EXPERIMENTAL

Patient Group: Patients who have failed at least one line of chemotherapy for metastatic disease. Treatment: BNC101 administered in combination with FOLFIRI Participants will be treated until disease progression, intolerable toxicity, withdrawal of consent, or study termination by the Sponsor, whichever occurs first.

Drug: BNC101 in combination with FOLFIRI

Interventions

BNC101 Solution for Infusion DRUG

Administration: Administered via IV infusion once a week over 60 minutes (1 hour).

Also known as: BNC101

Group/Stream 1 - Monotherapy

BNC101 in combination with FOLFIRI DRUG

BNC101 - Starting dose as determined by Arm A portion (one dose level below recommended Phase 2 dose). BNC101 Administration: Administered via IV Infusion once a week over 60 minutes (1 hour). FOLFIRI components: Irinotecan (IRI) - Starting dose 180 mg/m2 (over 90 minutes on Day 1) Leucovorin (LV) - Starting dose 400 mg/m2 (administered over 120 minutes on Day 1 concurrently with IRI) 5-FU bolus - Starting dose 400 mg/m2 (administered after LV on Day 1, then) 5-FU infusion - Starting dose 2400 mg/m2 (administered over 48 hours starting on Day 1) FOLFIRI Cycles are repeated every 14 days.

Also known as: FOLFIRI

Group/Stream 2 - Combination Chemo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed written Informed Consent
• Age \> 18 years
• Eastern Cooperative Oncology Group (ECOG) score 0 - 1.
• Histologically or cytologically confirmed colorectal cancer patients who have failed at least 2 lines of chemotherapy (monotherapy treatment cohorts) or at least 1 line of chemotherapy (combination treatment cohorts) for metastatic disease, and in the opinion of both physician and patient it is not unreasonable to try experimental therapy. Adjuvant FOLFOX within the last 6 months is considered a line of therapy. A maintenance strategy post 1st line treatment is not considered as an additional line of therapy.
• Patients must have accessible tumor lesions amenable to biopsy which would not put the patient or their treatment at risk. Patients in monotherapy escalation cohort 3 and onwards, the monotherapy expansion cohort, and all combination treatment patients, agree and are willing to provide 2 serial tumor lesion biopsies (a minimum of 2 fresh cores/punches preferred whenever possible). Biopsies can be from liver metastases, in lieu of the primary tumor. The presence of tumor tissue in fresh biopsies is to be certified by a trained pathologist using appropriate extemporaneous histology or cytology procedures. Refer to Appendix 6 for biopsy procedures.
• All AEs of any prior chemotherapy, surgery, or radiotherapy, must have resolved to Grade ≤ 1.
• Measurable or evaluable disease per RECIST version 1.1.
• Life expectancy of at least \> 12 weeks.
• Normal organ and marrow function:
• Absolute neutrophil count (ANC) \> 1,500/mL without growth factor support in the past 14 days prior to enrolment
• Platelets \> 100,000/mL without transfusions in the past 14 days prior to enrolment
• Hemoglobin \> 9.0 g/dL - Patients may be transfused or receive erythropoietic treatment to meet this criterion
• Total bilirubin \< 1.5 x institutional upper limit of normal (ULN) (\< 2 x ULN for subjects with Gilbert's syndrome)
• Serum albumin ≥ 3 g/dL.
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase, SGOT) and alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase, SGPT) \< 2.5 x institutional ULN (for subjects with hepatic involvement \< 5 x institutional ULN but cannot be associated with elevated bilirubin).

You may not qualify if:

• Inability to comply with study and follow-up procedures (including, but not limited to: geographical or administrative reasons, and planned vacation absences for more than 7 consecutive days during the study).
• Women who are pregnant or lactating.
• Colorectal cancer patients going on to receive 1st line therapy for metastatic disease.
• Treatment with chemotherapy, immunotherapy, biologic therapy, or radiation therapy as cancer therapy within 4 weeks before initiation of study treatment. Six weeks should have elapsed if prior chemotherapy treatment included nitrosoureas or mitomycin C.
• Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days prior to Day 1 of Cycle 1.
• Patients who have received antibody-based therapies within 28 days or 5 half-lives of the agent, whichever is longer.
• Major surgery, other than diagnostic surgery, within 6 weeks before first study drug administration.
• Clinically detectable (by physical exam) third-space fluid collections (e.g., ascites or pleural effusion) that cannot be controlled by drainage or other procedures prior to study entry.
• Any uncontrolled medical or psychiatric risk factors which would contraindicate the use or impair the ability of the patient to provide informed consent, receive protocol therapy or may impose excessive risk to the patient.
• Central nervous system (CNS) metastases, unless previously treated and well-controlled for at least 3 months (defined as clinically stable, no edema, no steroids and stable in 2 scans at least 4 weeks apart). Patients who display signs or symptoms of CNS metastases or should be imaged with CT or magnetic resonance imaging (MRI) of the head. Should metastases, including meningeal deposits be detected, these patients will not be treated with BNC101.
• Current use of medications that may have the potential of QTc prolongation (refer to Appendix 1). If the need for use of these medications arises during the study, a discussion with and approval by the sponsor would be required.
• History of allergy or hypersensitivity to Chinese Hamster Ovary cell products, any compound of the BNC101 formulation, or any of the chemotherapy agents to be used in this study.
• Active uncontrolled bacterial, viral, or fungal infection, requiring systemic therapy.
• Patient has known infection with human immunodeficiency virus (HIV), Hepatitis B or Hepatitis C, alcoholic or other hepatitis, or cirrhosis.
• Inability to be venipunctured and/or tolerate venous access.

Sponsors & Collaborators

• Bionomics Limited: lead
• CPR Pharma Services Pty Ltd, Australia: collaborator

Study Sites (4)

Flinders Medical Centre

Bedford Park, South Australia, 5042, Australia

Location

Monash Health

Clayton, Victoria, 3168, Australia

Location

Austin Health

Heidelberg, Victoria, 3084, Australia

Location

Royal Melbourne Hospital

Melbourne, Victoria, 3050, Australia

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Neoplasm Metastasis

Interventions

IFL protocol

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 28, 2016
• First Posted: April 1, 2016
• Study Start: March 1, 2016
• Primary Completion: December 1, 2017
• Study Completion: February 1, 2018
• Last Updated: January 16, 2019

Record last verified: 2019-01

Locations

AU (4)