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

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ClinicalTrials.gov Identifier: NCT02483247
Recruitment Status : Active, not recruiting
First Posted : June 26, 2015
Last Update Posted : April 3, 2018
Sponsor:
Information provided by (Responsible Party):
Boston Biomedical, Inc

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.

Condition or disease Intervention/treatment Phase
Cancer Drug: BBI503 Drug: Capecitabine Drug: Doxorubicin Drug: Nivolumab Drug: Pembrolizumab Drug: Paclitaxel Drug: Sunitinib Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase Ib/II Clinical Study of BBI503 in Combination With Selected Anti-Cancer Therapeutics in Adult Patients With Advanced Cancer
Study Start Date : September 2015
Estimated Primary Completion Date : December 2018

Arm Intervention/treatment
Experimental: Combo with Capecitabine Drug: BBI503
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.
Other Names:
  • amcasertib
  • BBI-503
  • BB503

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

Experimental: Combo with Doxorubicin Drug: BBI503
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.
Other Names:
  • amcasertib
  • BBI-503
  • BB503

Drug: Doxorubicin
Doxorubicin 60 mg/m^2 body surface area is administered intravenously once every three weeks (21-days).
Other Names:
  • Doxil
  • Adriamycin

Experimental: Combo with Nivolumab (US only) Drug: BBI503
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.
Other Names:
  • amcasertib
  • BBI-503
  • BB503

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

Experimental: Combo with Pembrolizumab Drug: BBI503
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.
Other Names:
  • amcasertib
  • BBI-503
  • BB503

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

Experimental: Combo with Paclitaxel Drug: BBI503
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.
Other Names:
  • amcasertib
  • BBI-503
  • BB503

Drug: Paclitaxel
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.
Other Name: Taxol

Experimental: Combo with Sunitinib Drug: BBI503
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.
Other Names:
  • amcasertib
  • BBI-503
  • BB503

Drug: Sunitinib
Sunitinib 37.5 mg is administered once daily.
Other Name: Sutent




Primary Outcome Measures :
  1. Determination of the safety and tolerability of BBI503 administered in combination with selected anti-cancer therapeutics by assessing dose-limiting toxicities (DLTs) [ Time Frame: 3 or 4 weeks based on the cycle of the selected anti-cancer therapeutics ]
  2. Determination of the Recommended Phase 2 Dose (RP2D) by assessing dose-limiting toxicities (DLTs) [ Time Frame: 3 or 4 weeks based on the cycle of the selected anti-cancer therapeutics ]

Secondary Outcome Measures :
  1. Assessment of the preliminary anti-tumor activity by performing tumor assessments every 8 weeks (Phase 2 portion) [ Time Frame: 6 months ]
    Evaluation of anti-tumor activity will be performed according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.

  2. Pharmacokinetic profile of BBI503 administered in combination with selected anti-cancer therapeutics as assessed by maximum plasma concentration and area under the curve [ Time Frame: 0, 1, 2, 3, 4, 6, 8, 10, 24 hours on day 1, cycles 1 and 2 ]
  3. Pharmacodynamic activity of BBI503 administered in combination with selected anti-cancer therapeutics as assessed by biomarker analysis [ Time Frame: 3 or 4 weeks based on the cycle of the selected anti-cancer therapeutics ]
    Histopathology and Cancer Stem Cell assays will be performed to provide information of the biomarkers on biopsied patient tumor tissue, and archival samples.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Major inclusion criteria:

  1. 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.
  2. Must be ≥ 18 years of age
  3. Has disease such that progression or response to therapy can be evaluated objectively while on protocol.
  4. Must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  5. 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.
  6. Females of childbearing potential must have a negative serum pregnancy test.
  7. 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.
  8. Hemoglobin (Hgb) ≥ 9 g/dl
  9. 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
  10. 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).
  11. Absolute neutrophil count ≥ 1.5 × 10^9/L
  12. Platelets ≥ 100 × 10^9/L
  13. Life expectancy ≥ 3 months

Major exclusion criteria:

  1. 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.
  2. 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)
  3. 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.
  4. Pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study.
  5. 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).
  6. 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.
  7. 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).
  8. 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
  9. 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.
  10. 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
  11. 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
  12. For patients to be treated with a regimen containing doxorubicin: a) Known left ventricular ejection fraction < 50%, b) Hypersensitivity to doxorubicin
  13. 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02483247


Locations
United States, Indiana
Parkview Research Center
Fort Wayne, Indiana, United States
Indiana University Health Goshen
Goshen, Indiana, United States, 46526
Indiana University -Ball
Indianapolis, Indiana, United States
Indiana University-SCC
Indianapolis, Indiana, United States
United States, Louisiana
Louisiana State Univesity
New Orleans, Louisiana, United States
United States, Virginia
US Oncology Research
Fairfax, Virginia, United States
Canada, Ontario
Ottawa Hospital Research Institute
Ottawa, Ontario, Canada
Princess Margaret Cancer Centre
Toronto, Ontario, Canada
Sponsors and Collaborators
Boston Biomedical, Inc

Responsible Party: Boston Biomedical, Inc
ClinicalTrials.gov Identifier: NCT02483247     History of Changes
Other Study ID Numbers: BBI503-201
First Posted: June 26, 2015    Key Record Dates
Last Update Posted: April 3, 2018
Last Verified: March 2018

Keywords provided by Boston Biomedical, Inc:
Neoplasms

Additional relevant MeSH terms:
Paclitaxel
Liposomal doxorubicin
Pembrolizumab
Nivolumab
Sunitinib
Albumin-Bound Paclitaxel
Capecitabine
Doxorubicin
Coal Tar
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Keratolytic Agents
Dermatologic Agents