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

NCT03328494 | Completed Phase 1 DMC

• 2 other identifiers: BOS172722-012017-001749-29
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 3

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.

Conditions

Advanced Nonhaematologic Malignancies

Keywords

Paclitaxel; BOS172722; triple-negative breast cancer

Outcome Measures

Primary Outcomes (2)

• Incidence of adverse events (AEs)

  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.

  a minimum of approximately 3 months

• Number of participants with a dose-limiting toxicity (DLT)

  A DLT is defined as any toxicity attributable to BOS172722 that occurs before the end of Cycle 1.

  Cycle 1 (28 days)

Secondary Outcomes (7)

• Part A Monotherapy: Plasma concentration of BOS172722 measured over 24 hours when administered alone

  Cycle 1: Day 1

• Part A Combination: Plasma concentration of BOS172722 and paclitaxel measured over 24 hours when administered either individually or in combination

  Cycle 0: Day 1; Cycle 1: Day 1; Cycle 2: Day 1

• Part B Expansion: Plasma concentration of BOS172722 and paclitaxel measured over 24 hours when administered in combination

  Cycle 1: Days 1 and 8 or 15

• Objective response rate (ORR)

  a minimum of approximately 3 months

• Duration of response (DOR)

  a minimum of approximately 3 months

Study Arms (3)

Part A: Monotherapy (BOS172722)

EXPERIMENTAL

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.

Drug: BOS172722

Part A: Combination therapy (BOS172722 + Paclitaxel)

EXPERIMENTAL

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.

Drug: BOS172722; Drug: Paclitaxel

Part B: Combination therapy (BOS172722 + Paclitaxel)

EXPERIMENTAL

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.

Drug: BOS172722; Drug: Paclitaxel

Interventions

BOS172722 DRUG

Oral capsules

Part A: Combination therapy (BOS172722 + Paclitaxel); Part A: Monotherapy (BOS172722); Part B: Combination therapy (BOS172722 + Paclitaxel)

Paclitaxel DRUG

IV infusion

Part A: Combination therapy (BOS172722 + Paclitaxel); Part B: Combination therapy (BOS172722 + Paclitaxel)

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Boston Pharmaceuticals: lead

Study Sites (3)

Addenbrooks Hospital

Cambridge, United Kingdom

Location

Edinburgh Cancer Centre - Western General Hospital

Edinburgh, United Kingdom

Location

Royal Marsden

London, SM2 5NG, United Kingdom

Location

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

BOS172722; Paclitaxel

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Design

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

Study Record Dates

• First Submitted: October 30, 2017
• First Posted: November 1, 2017
• Study Start: October 13, 2017
• Primary Completion: March 16, 2021
• Study Completion: March 16, 2021
• Last Updated: April 15, 2021

Record last verified: 2021-04

Locations

GB (3)