BP31510 (Ubidecarenone,USP) Nanosuspension for Intravenous Injection to Patients With Solid Tumors

NCT01957735 | Completed Phase 1 FDA Drug

• 1 other identifier: BP-31510IV-04
• Study Type: interventional
• Target: 97
• Locations: 1 country
• Sites: 3

Brief Summary

This is a Phase 1a/b multicenter, open-label, non-randomized, dose-escalation study to examine the dose limiting toxicities (DLT) of BPM31510 administered as a 144-hour continuous intravenous (IV) infusion as monotherapy(treatment Arm 1) and in combination with chemotherapy (treatment Arm 2) in patients with solid tumors.

Conditions

Metastatic Cancer; Cancer; Solid Tumor

Keywords

metastatic cancer; solid tumor; unresectable tumor; brain cancer; lymphoma

Outcome Measures

Primary Outcomes (1)

• Determine Maximum Tolerated Dose (MTD) of BP31510

  Dose limiting toxicities will be assessed during Cycle 1 (first four weeks of Arm 1 and 6 weeks for Arm 2) of the study. Blood samples for pharmacokinetic and pharmacodynamic analyses will be collected during each cycle of monotherapy and combination therapy. Urine samples for determination of BPM31510 renal clearance will be collected only during Cycle 1 of monotherapy and combination therapy. A PET scan will be performed within 2 weeks prior to starting treatment and after 2 weeks of BPM31510 treatment, and 8 weeks of treatment on Arm 1 or 10 weeks of treatment on Arm 2. Core biopsies (2-3) will be performed at the time of baseline and Week 2 PET scan for patients who opt-in to participate in these exploratory studies.

  Wach week of treatment for the duration of Cycle 1 up to 4 weeks on Arm 1 and 6 weeks for Arm 2

Secondary Outcomes (2)

• To evaluate plasma pharmacokinetics (PK) of BPM31510

  Each cycle (every 4 weeks) for for up to 1 year

• To estimate renal clearance of BPM31510

  Each cycle (every 4 weeks) for for up to 1 year

Study Arms (2)

BP31510 monotherapy

EXPERIMENTAL

* Starting dose level of BPM31510 will be 66 mg/kg administered by IV infusion over 48 hours 2 times per week of each 28-day cycle.The 2 doses will be administered over 4 consecutive days.The study drug will be administered undiluted via a central venous access device and the infusion rate will be controlled by a programmable ambulatory infusion pump. * first dose of each week of the cycle a loading dose will be infused over 1 hour with the remainder of the dose volume infused over 47 hours.At each dose level of Arm 1 and Arm 2, patients will be treated for either 8 hours at minimum of outpatient monitoring or inpatient monitoring for the first 24-hrs of the first infusion of Cycle 1. * second dose of each week of the cycle, the total dose volume given over 48 hours with no loading dose.

Drug: BP31510 monotherapy

BP31510 in combination with chemotherapy

ACTIVE COMPARATOR

standard 3+3 design will be used for Arm 2 of the study. BPM31510 will be started at one dose level below the dose that has been studied and determined to be safe in the monotherapy portion of the trial. Arm 2 patients will be enrolled onto one of 3 chemotherapies, gemcitabine, 5-FU, or docetaxel according to the dose levels below: * Gemcitabine IV once weekly at a starting dose of 600 mg/m2 ; * 5-Fluorouracil (5-FU) IV once weekly at a starting dose of 350 mg/m2 with leucovorin (LV) 100 mg/m2; OR * Docetaxel IV once weekly at a starting dose of 20 mg/m2. * Note:Both BPM31510 and the chemotherapy agent can escalate simultaneously in Cohorts 3 and 4 only if there are no DLTs observed in the previous cohorts. If one or more DLTs are observed, then intermediate dose levels will be added where one agent is escalated.

Drug: BP31510 in combination with chemotherapy

Interventions

BP31510 monotherapy DRUG

BP31510 monotherapy

BP31510 in combination with chemotherapy DRUG

BP31510 in combination with chemotherapy

Eligibility Criteria

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

You may qualify if:

• The patient has a histologically confirmed solid tumor that is metastatic or unresectable for which standard measures do not exist or are no longer effective. (Patients with primary brain cancer or lymphoma are permitted. Patients with brain metastases are allowed if whole brain radiation was performed and is documented stable for ≥ 6 weeks)
• The patient is at least 18 years old.
• The patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• The patient has a life expectancy of \> 3 months.
• Sexually active patients and their partners agree to use an accepted method of contraception during the course of the study
• Female patients of childbearing potential must have a negative pregnancy test within 1 week prior to beginning study treatment.
• The patient has adequate organ and marrow function as follows:
• ANC ≥ 1500 mm3, platelets ≥ 100,000/mm3, hemoglobin ≥ 9 g/dL,
• serum creatinine ≤1.8 mg/dL or creatinine clearance \> 50 mL/min (Appendix I);
• bilirubin ≤ 1.5 mg/dL; alanine aminotransferase (ALT), aspartate transaminase (AST) ≤ 2.5 times the upper limit of normal if no liver involvement or ≤ 5 times the upper limit of normal with liver involvement.
• The patient has serum electrolytes (including calcium, magnesium, phosphorous, sodium and potassium) within normal limits (supplementation to maintain normal electrolytes is allowed).
• The patient has adequate coagulation: prothrombin time (PT), partial thromboplastin time (PTT), and an International Normalized Ratio within normal limits.
• The patient is capable of understanding and complying with the protocol and has signed the informed consent document.

You may not qualify if:

• The patient has uncontrolled intercurrent illness including, but not limited to uncontrolled infection, symptomatic congestive heart failure (NYHA class III and IV), uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• The patient has active heart disease including myocardial infarction within previous 3 months, symptomatic coronary artery disease, arrhythmias not controlled by medication, unstable angina pectoris, or uncontrolled congestive heart failure (NYHA class III and IV)
• The patient has received chemotherapy or radiotherapy within 4 weeks or has received nitrosoureas or mitomycin C within 6 weeks prior to the first dose of study drug.
• The patient has received radiation to ≥ 25% of his or her bone marrow within 4 weeks of the first dose of study drug.
• The patient has received an investigational drug within 30 days of the first dose of study drug.
• The patient has not recovered to grade ≤ 1 adverse events (AEs) due to investigational drugs or other medications, administered more than 2 weeks prior to the first dose of study drug, with the exception of neurotoxicity attributed to oxaliplatin or taxanes, which must have recovered to \< 2 prior to study initiation.
• The patient is pregnant or lactating.
• The patient is known to be positive for the human immunodeficiency virus (HIV). The effect of BPM31510 on HIV medications is unknown. Note: HIV testing is not required for eligibility, but if performed previously and was positive, the patient is ineligible for the study.
• The patient has an inability or unwillingness to abide by the study protocol or cooperate fully with the investigator or designee.
• The patient is receiving digoxin, digitoxin, lanatoside C or any type of digitalis alkaloids.
• The patient is receiving colony stimulating factors (CSFs) that cannot be held during the monitoring period for dose-limiting toxicities (DLT).
• The patient has uncontrolled or severe coagulopathies or a history of clinically significant bleeding within the past 6 months, such as hemoptysis, epistaxis, hematochezia, hematuria, or gastrointestinal bleeding.
• The patient has a known predisposition for bleeding such as von Willebrand's disease or other such condition.
• The patient requires therapeutic doses of any anticoagulant, including LMWH. Concomitant use of warfarin, even at prophylactic doses, is prohibited.

Sponsors & Collaborators

• BPGbio: lead

Study Sites (3)

Palo Alto Medical Foundation

Sunnyvale, California, 94086, United States

Location

Weill Cornell Solid Tumor Oncology Practice

New York, New York, 10021, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Neoplasm Metastasis; Neoplasms; Brain Neoplasms; Lymphoma

Interventions

Drug Therapy

Condition Hierarchy (Ancestors)

Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Manish A Shah, MD

  Weill Cornell Solid Tumor Oncology Practice

  PRINCIPAL INVESTIGATOR

• Vivek Subbiah, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

• Kim-Son Nguyen, MD

  Palo Alto Medical Foundation

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: August 9, 2013
• First Posted: October 8, 2013
• Study Start: October 1, 2013
• Primary Completion: February 1, 2017
• Study Completion: February 1, 2017
• Last Updated: February 19, 2025

Record last verified: 2019-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)