Safety, Efficacy, and Tolerability of BOS172738 in Patients With Advanced Rearranged During Transfection (RET) Gene-Altered Tumors
- Registration Number
- NCT03780517
- Lead Sponsor
- Boston Pharmaceuticals
- Brief Summary
This study will be conducted to assess the safety and tolerability of BOS172738 when administered to patients with advanced solid tumors with rearranged during transfection (RET) gene alterations and also to establish the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of BOS172738.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 117
Participants are eligible to be included in the study only if all of the following criteria apply:
- Male or female participants must be ≥ 18 years, at the time of signing the informed consent
- Diagnosis of advanced solid tumor with a documented rearranged during transfection (RET) gene altered malignancy as determined locally by a DNA based assay of tumor tissue and/or blood
- Participants must have no alternative approved therapy.
- For participants in Part B expansion cohort only: documented local diagnosis of either 1) advanced RET gene fusion non-small cell lung cancer (NSCLC); 2) advanced RET gene mutant medullary thyroid cancer (MTC); or 3) other RET gene altered advanced tumors or NSCLC/MTC with prior specific RET gene targeted therapy
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Negative pregnancy test for females of child bearing potential; must be surgically sterile, postmenopausal, or willing and able to be compliant with a contraceptive regimen
- Contraceptive use by men or women should be consistent with local regulations.
- Capable of giving signed informed consent
Participants are excluded from the study if any of the following criteria apply:
- Inability to take oral medications or gastrointestinal (GI) conditions that can interfere with the swallowing or absorption of study medication
- Uncontrolled or severe concurrent medical condition
- History of upper GI bleeding, ulceration, or perforation within 12 months prior to the first dose of study drug
- Known history of stroke or cerebrovascular accident within 6 months prior to the first dose of study drug
- Participants with known infection with human immunodeficiency virus (HIV) or Acquired Immune Deficiency Syndrome (AIDS) (testing not required)
- Participants who are hepatitis B surface antigen positive or participants who are hepatitis C antibody positive (Participants who have been successfully treated for hepatitis C virus [HCV] are eligible if an undetectable HCV viral load at least 6 months after completion of treatment can be demonstrated.)
- Any evidence of serious active infections
- Uncontrolled or severe cardiovascular disease
- Uncontrolled intercurrent illness or psychiatric illness/social situations that would limit compliance with study requirements
- Participants with a prior or concurrent malignancy other than the malignancies under study
- Ongoing cancer directed therapy
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description BOS172738 BOS172738 In Part A (dose escalation), participants with advanced solid tumors with rearranged during transfection (RET) gene alterations will receive oral BOS172738 at a starting dose of 10 milligrams (mg) once daily in each 28-day cycle. In Part B (dose expansion), participants with RET gene-fusion non-small cell lung cancer (NSCLC), with RET gene-mutant medullary thyroid cancer (MTC), and with RET gene-altered advanced tumors or NSCLC/MTC with prior specific RET gene-targeted therapy will be enrolled in Cohorts 1, 2, and 3, respectively, and will receive oral BOS172738 once daily in each 28-day cycle at the recommended Phase 2 dose (RP2D) established in Part A.
- Primary Outcome Measures
Name Time Method Number of participants with any non-serious TEAE a minimum of approximately 3 months Number of participants with grade 3, grade 4, or grade 5 TEAEs a minimum of approximately 3 months Number of participants with any related TEAE a minimum of approximately 3 months Number of participants with any treatment-emergent (TE) serious adverse event (SAE) a minimum of approximately 3 months Number of participants with any TEAE leading to study drug discontinuation a minimum of approximately 3 months Maximum tolerated dose (MTD) of BOS172738 throughout Cycle 1 (each cycle is 28 days) Recommended phase 2 dose (RP2D) of BOS172738 28-day cycles in Part A (minimum of one dose of BOS172738 received)
- Secondary Outcome Measures
Name Time Method Objective Disease Control Rate (ODCR) a minimum of approximately 3 months Duration of Response (DoR) a minimum of approximately 3 months Time to Response (TTR) a minimum of approximately 3 months Duration of Complete Response (DoCR) a minimum of approximately 3 months Objective Response Rate (ORR) a minimum of approximately 3 months Progression-Free Survival (PFS) a minimum of approximately 3 months Part A: Plasma concentration of BOS172738 Pre-dose on Days 1, 2, 15, and 16 of Cycle 1; Day 1 of Cycles 2, 3, and 4. 15 minutes (min); 30 min; 1, 3, 6, 8, 10, and 12 hours after the BOS1722722 dose on Days 1 and 15 of Cycle 1 (each cycle is 28 days) Part B: Plasma concentration of BOS172738 Pre-dose on Day 1 of Cycles 2, 3, and 4 (each cycle is 28 days)
Trial Locations
- Locations (21)
Centre Léon Bérard
🇫🇷Lyon, France
Institut Bergonié
🇫🇷Bordeaux, France
Chungbuk National University Hospital
🇰🇷Cheongju-si, Korea, Republic of
Severance Hospital, Yonsei University College of Medicine
🇰🇷Seoul, Korea, Republic of
Institut Gustave Roussy
🇫🇷Villejuif, France
Start Madrid - Ciocc
🇪🇸Madrid, Spain
Institut Jules Bordet
🇧🇪Bruxelles, Belgium
Hospital Germans Trias i Pujol
🇪🇸Badalona, Spain
Korea University Anam Hospital
🇰🇷Seoul, Korea, Republic of
START MADRID-FJD, Hospital Fundación Jiménez Díaz
🇪🇸Madrid, Spain
Hospital Universitario Virgen de la Victoria
🇪🇸Málaga, Andalucia, Spain
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
UZ Leuven
🇧🇪Leuven, Belgium
Seoul National University Bundang Hospital
🇰🇷Gyeonggi-do, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Fox Chase Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Taichung Veterans General Hospital
🇨🇳Taichung, Taiwan
Hôpital Pitié-Salpêtrière
🇫🇷Paris, France
Instituto Oncológico Dr. Rosell, S.L.
🇪🇸Barcelona, Spain
Prince of Wales Hospital
🇭🇰Hong Kong, Hong Kong