Clinical trial NCT03780517: Safety, Efficacy, and Tolerability of BOS172738 in Patients With Advanced Rearranged During Transfection (RET) Gene-Altered Tumors
Official title: A Phase 1 Study of BOS172738 in Patients With Advanced Solid Tumors With RET Gene Alterations Including Non-Small Cell Lung Cancer (NSCLC) and Medullary Thyroid Cancer (MTC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Nonhaematologic Malignancies
Keywords: BOS172738
RET gene
Medullary Thyroid Cancer
Non-Small Cell Lung Cancer
Lead sponsor: Boston Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2018-12-19
Enrollment: 117
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

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

Primary outcomes:
measure: Number of participants with any treatment-emergent (TE) serious adverse event (SAE)
timeFrame: a minimum of approximately 3 months
measure: Number of participants with any non-serious TEAE
timeFrame: a minimum of approximately 3 months
measure: Number of participants with grade 3, grade 4, or grade 5 TEAEs
timeFrame: a minimum of approximately 3 months
measure: Number of participants with any related TEAE
timeFrame: a minimum of approximately 3 months
measure: Number of participants with any TEAE leading to study drug discontinuation
timeFrame: a minimum of approximately 3 months
measure: Maximum tolerated dose (MTD) of BOS172738
timeFrame: throughout Cycle 1 (each cycle is 28 days)
measure: Recommended phase 2 dose (RP2D) of BOS172738
timeFrame: 28-day cycles in Part A (minimum of one dose of BOS172738 received)
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: a minimum of approximately 3 months
measure: Objective Disease Control Rate (ODCR)
timeFrame: a minimum of approximately 3 months
measure: Progression-Free Survival (PFS)
timeFrame: a minimum of approximately 3 months
measure: Duration of Response (DoR)
timeFrame: a minimum of approximately 3 months
measure: Time to Response (TTR)
timeFrame: a minimum of approximately 3 months
measure: Duration of Complete Response (DoCR)
timeFrame: a minimum of approximately 3 months
measure: Part A: Plasma concentration of BOS172738
timeFrame: 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)
measure: Part B: Plasma concentration of BOS172738
timeFrame: Pre-dose on Day 1 of Cycles 2, 3, and 4 (each cycle is 28 days)
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Bruxelles
country: Belgium
facility: Institut Jules Bordet
city: Leuven
country: Belgium
facility: UZ Leuven
city: Bordeaux
country: France
facility: Institut Bergonié
city: Lyon
country: France
facility: Centre Léon Bérard
city: Paris
country: France
facility: Hôpital Pitié-Salpêtrière
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Hong Kong
country: Hong Kong
facility: Prince of Wales Hospital
city: Cheongju-si
country: Korea, Republic of
facility: Chungbuk National University Hospital
city: Gyeonggi-do
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University College of Medicine
city: Málaga
country: Spain
facility: Hospital Universitario Virgen de la Victoria
state: Andalucia
city: Badalona
country: Spain
facility: Hospital Germans Trias i Pujol
city: Barcelona
country: Spain
facility: Instituto Oncológico Dr. Rosell, S.L.
city: Madrid
country: Spain
facility: Start Madrid - Ciocc
city: Madrid
country: Spain
facility: START MADRID-FJD, Hospital Fundación Jiménez Díaz
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
Study officials:
References: