A Study of BBI503 in Combination With Selected Anti-Cancer Therapeutics in Adult Patients With Advanced Cancer

NCT02483247 | Completed Phase 1

• 1 other identifier: BBI503-201
• Study Type: interventional
• Target: 165
• Locations: 2 countries
• Sites: 8

Brief Summary

This is an open label, multi-center, Phase 1/2 study of BBI503 administered in combination with selected anti-cancer therapeutics in adult patients with advanced cancer. The goal of the study is to determine the safety, tolerability, and RP2D of BBI503 in combination with each of the selected anti-cancer agents.

Conditions

Cancer

Keywords

Neoplasms

Outcome Measures

Primary Outcomes (2)

• Determination of the safety and tolerability of BBI503 administered in combination with selected anti-cancer therapeutics by assessing dose-limiting toxicities (DLTs)

  3 or 4 weeks based on the cycle of the selected anti-cancer therapeutics

• Determination of the Recommended Phase 2 Dose (RP2D) by assessing dose-limiting toxicities (DLTs)

  3 or 4 weeks based on the cycle of the selected anti-cancer therapeutics

Secondary Outcomes (3)

• Assessment of the preliminary anti-tumor activity by performing tumor assessments every 8 weeks (Phase 2 portion)

  6 months

• Pharmacokinetic profile of BBI503 administered in combination with selected anti-cancer therapeutics as assessed by maximum plasma concentration and area under the curve

  0, 1, 2, 3, 4, 6, 8, 10, 24 hours on day 1, cycles 1 and 2

• Pharmacodynamic activity of BBI503 administered in combination with selected anti-cancer therapeutics as assessed by biomarker analysis

  3 or 4 weeks based on the cycle of the selected anti-cancer therapeutics

Study Arms (6)

Combo with Capecitabine

EXPERIMENTAL

Drug: BBI503; Drug: Capecitabine

Combo with Doxorubicin

EXPERIMENTAL

Drug: BBI503; Drug: Doxorubicin

Combo with Nivolumab (US only)

EXPERIMENTAL

Drug: BBI503; Drug: Nivolumab

Combo with Pembrolizumab

EXPERIMENTAL

Drug: BBI503; Drug: Pembrolizumab

Combo with Paclitaxel

EXPERIMENTAL

Drug: BBI503; Drug: Paclitaxel

Combo with Sunitinib

EXPERIMENTAL

Drug: BBI503; Drug: Sunitinib

Interventions

BBI503 DRUG

Patients in this trial will receive BBI503 orally, daily, and continuously. The dose-level of BBI503 will be assigned according to the dose-cohort open at the time the patient enrolls into a given arm. The study-arm and combination anti-cancer agent for a given patient will be determined by the investigator. BBI503 Dose Level 1: 200 mg once daily, Dose Level 2: 300 mg once daily.

Also known as: amcasertib, BBI-503, BB503

Combo with Capecitabine; Combo with Doxorubicin; Combo with Nivolumab (US only); Combo with Paclitaxel; Combo with Pembrolizumab; Combo with Sunitinib

Capecitabine DRUG

Capecitabine 1000 mg/m\^2 body surface area is administered orally, twice daily, on days 1-14 of each 21 day cycle.

Also known as: Xeloda

Combo with Capecitabine

Doxorubicin DRUG

Doxorubicin 60 mg/m\^2 body surface area is administered intravenously once every three weeks (21-days).

Also known as: Doxil, Adriamycin

Combo with Doxorubicin

Nivolumab DRUG

Nivolumab 3 mg/kg is administered as an intravenous infusion over 60 minutes on day 1 and day 15 of each 28 day cycle.

Also known as: Opdivo

Combo with Nivolumab (US only)

Pembrolizumab DRUG

Pembrolizumab 2 mg/kg is administered as an intravenous infusion over 30 minutes once every three weeks (21-days).

Also known as: Keytruda

Combo with Pembrolizumab

Paclitaxel DRUG

Paclitaxel 80 mg/m\^2 body surface area is administered intravenously once weekly on day 1, day 8, and day 15 of each 28 day cycle.

Also known as: Taxol

Combo with Paclitaxel

Sunitinib DRUG

Sunitinib 37.5 mg is administered once daily.

Also known as: Sutent

Combo with Sunitinib

Eligibility Criteria

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

You may qualify if:

• A histologically or cytologically confirmed solid tumor that is locally advanced, recurrent, or metastatic; for which curative resection is not currently possible; and for which systemic treatment with one of the selected anti-cancer agents is a reasonable therapeutic option.
• Must be ≥ 18 years of age
• Has disease such that progression or response to therapy can be evaluated objectively while on protocol.
• Must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Male or female patients of childbearing potential must agree to use contraception or avoidance of pregnancy measures during the study and for 30 days after the last dose.
• Females of childbearing potential must have a negative serum pregnancy test.
• Must have aspartate transaminase (AST) ≤ 2.5 × upper limit of normal (ULN) and alanine transaminase (ALT) ≤ 2.5 × ULN. Patients who do not have hepatocellular carcinoma but who have liver lesions or liver metastases may be eligible if AST ≤ 3.5 × ULN and AST ≤ 3.5 × ULN if agreed upon by the investigator and medical monitor for the sponsor.
• Hemoglobin (Hgb) ≥ 9 g/dl
• Total bilirubin ≤ 1.5 × ULN. For patients with liver lesions, total bilirubin ≤ 2.0 × ULN may be enrolled if agreed upon by the investigator and medical monitor for the sponsor
• Creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 60 mL/min/1.73 m\^2 for patients with creatinine levels above institutional upper limit of normal (using the Cockcroft-Gault equation).
• Absolute neutrophil count ≥ 1.5 × 10\^9/L
• Platelets ≥ 100 × 10\^9/L
• Life expectancy ≥ 3 months

You may not qualify if:

• Received anti-cancer chemotherapy, radiotherapy, immunotherapy, or investigational agents within 7 days of first dose of protocol therapy. Patients may begin protocol therapy on a date determined by the investigator and medical monitor for the sponsor after a minimum of 7 days since last receiving anti-cancer treatment, provided that all adverse events related to that have resolved or have been deemed irreversible.
• Major surgery within 4 weeks prior to first dose; major surgery is defined as a procedure requiring any of the following: general anesthesia, intubation and mechanical ventilation, or major incision (e.g., thoracotomy, laparotomy)
• Any known, untreated, brain metastases. Patients with treated brain metastases must have no clinical symptoms from the metastases, and must be either off steroids or on a stable dose of steroids ≤ 10 mg prednisone or equivalent for at least 2 weeks prior to protocol enrollment. Patients with known leptomeningeal metastases are excluded, even if treated.
• Pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study.
• Significant gastrointestinal disorder(s), in the opinion of the Principal Investigator, such as active inflammatory bowel disease, extensive gastric or small intestinal resection (which has resulted in short-gut syndrome or the inability to take oral medications).
• Unable or unwilling to swallow either BBI503 daily or an oral selected anti-cancer therapeutics; or, unwilling to receive intravenous injection of IV anti-cancer therapeutics.
• Positive for Human Immunodeficiency Virus (HIV), Hepatitis B (Hepatitis B Surface Antigen \[HBsAg\] reactive), or Hepatitis C virus (Hepatitis C Virus Ribonucleic Acid (HCV RNA\] (qualitative) is detected).
• Uncontrolled concurrent illness including, but not limited to: ongoing or active infection requiring therapy, clinically significant non-healing or healing wounds, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, significant pulmonary disease (shortness of breath at rest or on mild exertion), uncontrolled infection or psychiatric illness/social situations that would limit compliance with study requirements
• Subjects with a history of another primary cancer with the exception of: a) curatively resected non-melanoma skin cancer; b) curatively treated cervical carcinoma in situ; c) localized prostate cancer not requiring systematic therapy; and d) other primary cancer with no known active disease present, and no treatment administered in the 2 years prior to enrollment.
• For patients to be treated with a regimen containing capecitabine: a) Known hypersensitivity to capecitabine, b) Known dihydropyrimidine dehydrogenase (DPD) deficiency, c) Significant gastrointestinal disorder(s) that would, in the opinion of the Investigator, prevent absorption of an orally available agent
• For patients to be treated with a regimen containing sunitinib: a) Uncontrolled hypertension (systolic blood pressure \> 150 mmHg or diastolic pressure \> 90 mmHg despite optimal medical management), b) Evidence of bleeding diathesis or a clinically significant coagulopathy (≥ CTCAE Grade 3) within 4 weeks prior to the start of study, c) Recent hypoglycemia, d) Uncontrolled thyroid dysfunction despite optimal medical therapy
• For patients to be treated with a regimen containing doxorubicin: a) Known left ventricular ejection fraction \< 50%, b) Hypersensitivity to doxorubicin
• A patient to be treated with a regimen containing nivolumab or pembrolizumab will be excluded if the patient: a) Has an active autoimmune disease requiring immunosuppression with the exception of subjects with isolated vitiligo, resolved childhood asthma or atopic dermatitis, controlled hypoadrenalism or hypopituitarism, and euthyroid patients with a history of Grave's disease, b) Has had a previous life-threatening (CTCAE grade 4) immune-mediated adverse reaction; or, a previous severe (CTCAE grade 3) immune mediated adverse reaction that required treatment with corticosteroids (more than 10 mg/day prednisone or equivalent dose) for longer than 12 weeks, c) Has a transplanted organ, d) Has interstitial lung disease or active, non-infectious pneumonitis, e) Has received a live vaccine within 30 days prior to first dose, f) Previous severe hypersensitivity reaction to another monoclonal antibody (mAb), g) Has been treated with another monoclonal antibody ≤ 4 weeks before first dose.

Sponsors & Collaborators

• Sumitomo Pharma America, Inc.: lead

Study Sites (8)

Parkview Research Center

Fort Wayne, Indiana, United States

Location

Indiana University Health Goshen

Goshen, Indiana, 46526, United States

Location

Indiana University -Ball

Indianapolis, Indiana, United States

Location

Indiana University-SCC

Indianapolis, Indiana, United States

Location

Louisiana State Univesity

New Orleans, Louisiana, United States

Location

US Oncology Research

Fairfax, Virginia, United States

Location

Ottawa Hospital Research Institute

Ottawa, Ontario, Canada

Location

Princess Margaret Cancer Centre

Toronto, Ontario, Canada

Location

MeSH Terms

Conditions

Neoplasms

Interventions

Capecitabine; Doxorubicin; liposomal doxorubicin; Nivolumab; pembrolizumab; Paclitaxel; Sunitinib

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes; Pyrroles; Azoles; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Design

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

Study Record Dates

• First Submitted: June 24, 2015
• First Posted: June 26, 2015
• Study Start: September 1, 2015
• Primary Completion: May 1, 2019
• Study Completion: May 1, 2019
• Last Updated: November 14, 2023

Record last verified: 2023-11

Locations

US (6); CA (2)