Clinical Trials /

Study of Paclitaxel in Combination With BOS172722 in Patients With Advanced Nonhaematologic Malignancies

NCT03328494

Description:

This study will be conducted to assess the safety and tolerability of BOS172722 when administered as monotherapy and in combination with paclitaxel in participants with advanced nonhaematologic malignancies and also to establish the maximum tolerated dose and recommended Phase 2 dose of BOS172722 in combination with paclitaxel in those participants.

Related Conditions:
  • Breast Carcinoma
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of Paclitaxel in Combination With BOS172722 in Patients With Advanced Nonhaematologic Malignancies
  • Official Title: A Phase 1/1b Study of Paclitaxel in Combination With BOS172722, a Monopolar Spindle 1 Kinase Inhibitor, in Patients With Advanced Nonhaematologic Malignancies

Clinical Trial IDs

  • ORG STUDY ID: BOS172722-01
  • SECONDARY ID: 2017-001749-29
  • NCT ID: NCT03328494

Conditions

  • Advanced Nonhaematologic Malignancies

Interventions

DrugSynonymsArms
BOS172722Part A: Monotherapy (BOS172722)
PaclitaxelPart A: Combination therapy (BOS172722 + Paclitaxel)

Purpose

This study will be conducted to assess the safety and tolerability of BOS172722 when administered as monotherapy and in combination with paclitaxel in participants with advanced nonhaematologic malignancies and also to establish the maximum tolerated dose and recommended Phase 2 dose of BOS172722 in combination with paclitaxel in those participants.

Trial Arms

NameTypeDescriptionInterventions
Part A: Monotherapy (BOS172722)ExperimentalBOS172722 will be administered on Days 1, 2, 8, 9, 15, and 16 of each 28-day cycles in participants with histopathologically confirmed advanced nonhaematologic malignancies.
  • BOS172722
Part A: Combination therapy (BOS172722 + Paclitaxel)ExperimentalBOS172722 will be administered on Cycle 0 Day 1 and on Days 1, 2, 8, 9, 15, and 16 in Cycle 1 and subsequent 28-day cycles in participants with histopathologically confirmed advanced nonhaematologic malignancies. The participants will also receive 80 milligrams per meters squared (mg/m^2) paclitaxel as an intravenous (IV) infusion on Days 1, 8, and 15 of each 28-day cycle.
  • BOS172722
  • Paclitaxel
Part B: Combination therapy (BOS172722 + Paclitaxel)ExperimentalParticipants with triple-negative breast cancer will be treated with oral BOS172722 at the recommended Phase 2 dose (RP2D) established in Part A on Days 1, 2, 8, 9, 15, and 16 of each 28-day cycle and IV paclitaxel at 80 mg/m^2 on Days 1, 8, and 15 of each 28-day cycle.
  • BOS172722
  • Paclitaxel

Eligibility Criteria

        Inclusion Criteria:

        Participants are eligible to be included in the study only if all of the following criteria
        apply:

          -  For Part A only, histopathologically confirmed diagnosis of an advanced
             nonhaematologic malignancy

          -  For Part B only, histopathologically confirmed diagnosis of triple-negative breast
             cancer

          -  No alternative therapy of proven benefit or has refused standard treatment

          -  Eastern Cooperative Oncology Group performance status 0 or 1, measured within 72 hours
             before the first BOS172722 or paclitaxel dose

          -  Predicted life expectancy of ≥ 3 months

          -  Adequate renal function (creatinine ≤ 1.5 × upper limit of normal [ULN] or glomerular
             filtration rate ≥ 50 milliliters per minute [mL/min])

          -  Adequate hepatic function:

               -  Total bilirubin ≤ 1.5 × ULN

               -  Aspartate transaminase ≤ 3 × ULN (or ≤ 5 × ULN if due to liver involvement by
                  tumor)

               -  Alanine transaminase ≤ 3 × ULN (or ≤ 5 × ULN if due to liver involvement by
                  tumor)

          -  Adequate bone marrow function:

               -  Hemoglobin ≥ 9.0 grams per deciliter (g/dL)

               -  Platelet count ≥ 100 × 10^9 cells per liter (cells/L)

               -  Absolute neutrophil count ≥ 1.5 × 10^9 cells/L

          -  Mean corrected QT interval as calculated by the Fridericia correction formula < 470
             milliseconds

          -  Willingness to use adequate contraceptive methods

          -  Capable of giving signed informed consent

          -  Willingness to avoid direct sunlight and the use of tanning equipment during the study
             and for at least 30 days after the last BOS172722 dose

        Exclusion Criteria:

        Participants are excluded from the study if any of the following criteria apply:

          -  For Part A combination cohorts and Part B: a history of hypersensitivity to paclitaxel

          -  Persistent clinically significant toxicity from prior chemotherapy > Grade 1,
             excluding alopecia

          -  Unable to swallow oral capsules

          -  Gastrointestinal (GI) condition which could interfere significantly with the
             absorption of study medication

          -  History of upper GI bleeding, ulceration, or perforation within 6 months before the
             first or paclitaxel BOS172722 dose

          -  Uncontrolled or severe concurrent medical condition (including uncontrolled brain
             metastases). (Stable brain metastases either treated or being treated with a stable
             dose of steroids/anticonvulsants, with no dose change within 28 days before the first
             BOS172722 or paclitaxel dose, will be allowed.)

          -  History of stroke or cerebrovascular accident within 3 months before the first
             BOS172722 or paclitaxel dose

          -  Any evidence of serious active infection

          -  Uncontrolled or severe cardiovascular disease, including myocardial infarct or
             unstable angina within 6 months before the first BOS172722 or paclitaxel dose, New
             York Heart Association Class II or greater congestive heart failure, serious
             arrhythmias requiring medication for treatment, clinically significant pericardial
             disease, or cardiac amyloidosis

          -  Uncontrolled intercurrent illness or psychiatric illness/social situations that would
             limit compliance with study requirements

          -  Known infection with Human Immunodeficiency Virus or hepatitis A, B, or C (testing not
             required)

          -  Major surgery within 28 days before the first BOS172722 or paclitaxel dose

          -  Pregnant or breastfeeding

          -  Active treatment for a secondary malignancy

          -  Cancer-directed therapy (chemo-, radio-, immuno-, biologic, or hormonal therapy with
             the exception of luteinizing hormone-releasing hormone agonists/antagonists, receptor
             activator of nuclear factor kappa-B ligand inhibitors, and bisphosphonates) within 21
             days or 5 half-lives, whichever is longer, before the first BOS172722 or paclitaxel
             dose (Palliative radiotherapy is allowed before initiating study treatment if any
             associated toxicity resolved to ≤ Grade 1.)

          -  Use of a medication known to be a strong or moderate inhibitor or inducer of CYP3A4
             within 14 days before the first BOS172722 or paclitaxel dose

          -  Use of a medication known to be a substrate of CYP3A4 and to have a narrow therapeutic
             range within 14 days before the first BOS172722 or paclitaxel dose

          -  Consumption of grapefruit juice within 14 days before the first BOS172722 or
             paclitaxel dose
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of adverse events (AEs)
Time Frame:a minimum of approximately 3 months
Safety Issue:
Description:An AE is any untoward medical occurrence and does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an investigational product (IP), whether or not related to the IP. AEs include pre-existing conditions that worsen.

Secondary Outcome Measures

Measure:Part A Monotherapy: Plasma concentration of BOS172722 measured over 24 hours when administered alone
Time Frame:Cycle 1: Day 1
Safety Issue:
Description:The plasma concentration of BOS172722 when administered as monotherapy will be characterized
Measure:Part A Combination: Plasma concentration of BOS172722 and paclitaxel measured over 24 hours when administered either individually or in combination
Time Frame:Cycle 0: Day 1; Cycle 1: Day 1; Cycle 2: Day 1
Safety Issue:
Description:The plasma concentration of BOS172722 and paclitaxel will be characterized.
Measure:Part B Expansion: Plasma concentration of BOS172722 and paclitaxel measured over 24 hours when administered in combination
Time Frame:Cycle 1: Days 1 and 8 or 15
Safety Issue:
Description:The plasma concentration of BOS172722 and paclitaxel will be characterized.
Measure:Objective response rate (ORR)
Time Frame:a minimum of approximately 3 months
Safety Issue:
Description:ORR is defined as the percentage of participants achieving the best overall response of confirmed partial response (PR) or complete response (CR), as determined by investigator review. Responses are assessed by the Investigators using Response Evaluation Criteria in Solid Tumours (RECIST) guideline version 1.1.
Measure:Duration of response (DOR)
Time Frame:a minimum of approximately 3 months
Safety Issue:
Description:DOR is defined as the time from documentation of tumor response to disease progression. Responses are assessed by the Investigators using RECIST guideline version 1.1.
Measure:Time to response (TTR)
Time Frame:a minimum of approximately 3 months
Safety Issue:
Description:TTR is defined as the time from the start of treatment to the first objective tumor response observed for participants who achieved a CR or PR. Responses are assessed by the Investigators using RECIST guideline version 1.1.
Measure:Time to progression on study
Time Frame:a minimum of approximately 3 months
Safety Issue:
Description:Time to progression is defined as the time from treatment until objective tumor progression. This does not include deaths. Responses are assessed by the Investigators using RECIST guideline version 1.1.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Boston Pharmaceuticals

Trial Keywords

  • Paclitaxel
  • BOS172722
  • triple-negative breast cancer

Last Updated

October 30, 2017