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Gemcitabine

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* 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.

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.

BP31510 monotherapy

BP31510 in combination with chemotherapy

Manish A Shah, MD

Vivek Subbiah, MD

Kim-Son Nguyen, MD

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.

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.In the Phase 1a portion of the trial, patients who meet eligibility parameters will receive 2 consecutive 72-hour infusions of BPM31510 twice weekly on Tuesday and Friday (i.e., Days 1, 4, 8, 11, 18, 22 and 25), essentially receiving BPM31510 treatment for 144 hours per week of each 28-day cycle. 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.All other treatments will be administered in an outpatient setting.Dose limiting toxicities will be assessed during Cycle 1.

The study is a standard 3 + 3 dose escalation design with the dose escalated in successive cohorts of 3 to 6 patients each.Toxicity at each dose level will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE v4.02). Safety oversight will be provided by the Cohort Review Committee (CRC).The CRC will review and confirm all DLTs and will continue to monitor safety throughout the study (including Arm 2).

Assessments of the antitumor activity of BPM31510 will be performed at the end of Cycle 2 and every 2 cycles thereafter using standard techniques such as computerized tomography (CT) or magnetic resonance imaging (MRI) for patients with measurable disease.Response will be evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 .Patients who experience no unacceptable toxicity or disease progression, may receive additional 28-day cycles for up to 1 year on Arm 1 or 2. Patients on Arm 1 who progress may elect to continue BPM31510 treatment in combination with gemcitabine, 5-FU, or docetaxel at the treating physician's discretion. Once a dose level of BPM31510 monotherapy is evaluated and the CRC determines it safe to escalate to the next dose level, Cohort 1 of Treatment Arm 2 of BPM31510 in combination with chemotherapy will open to accrual. Cohort 1 of Arm 2 patients will be enrolled onto one of 3 chemotherapies, gemcitabine, 5-FU, or docetaxel. Cycle 1 of combination therapy (Arm 2) is 6 weeks in duration for patients with BPM31510 administered twice weekly on Tuesday and Friday for 6 weeks and chemotherapy administered on Mondays, Days 21, 28 and 35. Cycles 2-12 are 4 weeks in duration with BPM31510 administered twice weekly on Tuesday and Friday for 4 weeks and chemotherapy administered on Mondays, Days 7, 14 and 21. Dose limiting toxicities will be assessed during Cycle 1. Response will be assessed after Cycle 2 (10 weeks) and responders who continue onto Cycles 2-12 will be assessed every 2 cycles (8 weeks). Patients who progress and crossover to Arm 2 will be reconsented and must meet eligibility before restarting BPM31510. Crossover patients are not evaluated for DLTs on Arm 2 and all cycles of combination therapy are 4 weeks in duration (Cycles 1-12). BPM31510 is administered twice weekly on Tuesdays and Fridays for 4 weeks and chemotherapy administered on Mondays, Days 7, 14 and 21 for all crossover patients on Arm 2. Patients will continue BPM31510 in combination with chemotherapy for a maximum of 12 cycles in the absence of intolerable toxicity and progression. Patients on Arm 2 who progress on one type of chemotherapy may not switch to one of the other chemotherapy agents in combination with BPM31510.However, if the chemotherapy component (ie, 5-FU, gemcitabine, or docetaxel) of combination therapy is discontinued due to chemotherapy-related toxicity, patients may continue to receive BPM31510 as monotherapy.

Once the maximum tolerated dose (MTD) of BPM31510 as monotherapy and in combination with chemotherapy are established, an expansion cohort will be enrolled (a total of 12-15 patients for monotherapy and a total of 10 patients for each combination therapy).

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

A Phase 1a/b Non-randomized, Dose Escalation Study of the Safety, Pharmacokinetics, and Pharmacodynamics of Sterile BPM31510 (Ubidecarenone, USP) Nanosuspension Injection Administered Intravenously to Patients With Solid Tumors

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.

To evaluate plasma pharmacokinetics (PK) of BPM31510 monotherapy and BPM31510 in combination with chemotherapy when administered as a 144-hour IV infusion in patients with solid tumors.

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.

To estimate renal clearance of BPM31510 monotherapy and BPM31510 in combination with chemotherapy when administered as a 144-hour IV infusion in patients with solid tumors

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.

Berg, LLC

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
BP31510 (Ubidecarenone,USP) Nanosuspension for Intravenous Injection to Patients With Solid Tumors	NCT01957735	Metastatic Canc... Cancer Solid Tumor	BP31510 monothe... BP31510 in comb...	18 Years -	Berg, LLC
BP31510 (Ubidecarenone,USP) Nanosuspension for Intravenous Injection to Patients With Solid Tumors	NCT01957735	Metastatic Canc... Cancer Solid Tumor	BP31510 monothe... BP31510 in comb...	18 Years -	Berg, LLC

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