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

• ClinicalTrials.gov Identifier: NCT03328494
• Recruitment Status: Completed
• First Posted: November 1, 2017
• Last Update Posted: April 15, 2021
• Sponsor: Boston Pharmaceuticals
• Information provided by (Responsible Party): Boston Pharmaceuticals

Tracking Information

• First Submitted Date: October 30, 2017
• First Posted Date: November 1, 2017
• Last Update Posted Date: April 15, 2021
• Actual Study Start Date: October 13, 2017
• Actual Primary Completion Date: March 16, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 30, 2017)

• Incidence of adverse events (AEs) [ Time Frame: a minimum of approximately 3 months ]
  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.
• Number of participants with a dose-limiting toxicity (DLT) [ Time Frame: Cycle 1 (28 days) ]
  A DLT is defined as any toxicity attributable to BOS172722 that occurs before the end of Cycle 1.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 30, 2017)

• Part A Monotherapy: Plasma concentration of BOS172722 measured over 24 hours when administered alone [ Time Frame: Cycle 1: Day 1 ]
  The plasma concentration of BOS172722 when administered as monotherapy will be characterized
• 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 ]
  The plasma concentration of BOS172722 and paclitaxel will be characterized.
• 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 ]
  The plasma concentration of BOS172722 and paclitaxel will be characterized.
• Objective response rate (ORR) [ Time Frame: a minimum of approximately 3 months ]
  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.
• Duration of response (DOR) [ Time Frame: a minimum of approximately 3 months ]
  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.
• Time to response (TTR) [ Time Frame: a minimum of approximately 3 months ]
  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.
• Time to progression on study [ Time Frame: a minimum of approximately 3 months ]
  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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Advanced Nonhaematologic Malignancies

Intervention

• Drug: BOS172722
  Oral capsules
• Drug: Paclitaxel
  IV infusion

Study Arms

• Experimental: Part A: Monotherapy (BOS172722)
  BOS172722 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.
  Intervention: Drug: BOS172722
• Experimental: Part A: Combination therapy (BOS172722 + Paclitaxel)
  BOS172722 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. During dose escalation, further exploration of the treatment schedule for the BOS172722-paclitaxel combination will be initiated. In such combination cohorts, BOS172722 will be administered with paclitaxel on Days 1, 8, and 15 only of each treatment cycle (except for Cycle 2 Day1), and will not be administered on Day 2, 9, and 16. These alternative schedules will be explored to further characterize the pharmacokinetics and tolerability of such a dosing regimen.
  Interventions:

  • Drug: BOS172722
  • Drug: Paclitaxel
• Experimental: Part B: Combination therapy (BOS172722 + Paclitaxel)
  Participants 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.
  Interventions:

  • Drug: BOS172722
  • Drug: Paclitaxel

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 14, 2021): 38
• Original Estimated Enrollment (submitted: October 30, 2017): 68
• Actual Study Completion Date: March 16, 2021
• Actual Primary Completion Date: March 16, 2021 (Final data collection date for primary outcome measure)

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 standard curative treatment or has declined standard therapy
• 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 or Seville oranges (including juice, marmalade, etc.) within 14 days before the first BOS172722 or paclitaxel dose

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United Kingdom

Administrative Information

• NCT Number: NCT03328494
• Other Study ID Numbers: BOS172722-01; 2017-001749-29 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Boston Pharmaceuticals
• Original Responsible Party: Same as current
• Current Study Sponsor: Boston Pharmaceuticals
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Boston Pharmaceuticals
• Verification Date: April 2021