Actively Recruiting
A Phase 1/2 Study of CB-103 With Abemaciclib or Lenvatinib in Patients With NOTCH Activated Adenoid Cystic Carcinoma
Led by Glenn J. Hanna · Updated on 2025-06-17
32
Participants Needed
1
Research Sites
52 weeks
Total Duration
On this page
Sponsors
G
Glenn J. Hanna
Lead Sponsor
A
Adenoid Cystic Carcinoma Research Foundation
Collaborating Sponsor
AI-Summary
What this Trial Is About
This trial is studying patients with advanced adenoid cystic carcinoma (ACC) tumors that have an active NOTCH pathway mutation. The goal is to assess the effects of two different oral drug combinations on slowing tumor growth and improving survival. The study is a phase 2, open-label, non-randomized, parallel cohort trial involving the novel pan-NOTCH inhibitor CB-103 combined with either Abemaciclib, a CDK4/6 inhibitor, or Lenvatinib, a VEGFR tyrosine kinase inhibitor. This research focuses on patients with incurable or metastatic ACC. Participants will be assigned to one of two treatment groups: Cohort 1 will receive CB-103 combined with Abemaciclib, and Cohort 2 will receive CB-103 combined with Lenvatinib. The study uses a modified 3+3 dose escalation design to determine the dosing of CB-103 alongside the other medications. Treatment cycles last 28 days, where CB-103 is taken twice daily on five consecutive days each week followed by two days off. Abemaciclib or Lenvatinib is given according to standard care or study dosing schedules. Therapy continues until disease progression, intolerance, or participant withdrawal. Participants will undergo screening to confirm eligibility, followed by treatment visits including radiologic tumor scans and blood tests. Safety is monitored throughout the study with regular assessments. The main outcome measured is progression-free survival at 4 months for each cohort. Secondary outcomes include treatment-related side effects, overall response rate, overall survival, and duration of response over up to two years. Participation typically lasts about two years unless disease worsens or other reasons lead to stopping treatment.
CONDITIONS
Brief Title
CB-103 With Either Lenvatinib or Abemaciclib in Patients With NOTCH ACC
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Histologically confirmed adenoid cystic carcinoma (ACC) with recurrent, metastatic, or advanced incurable disease
- Activating mutation in the NOTCH signaling pathway
- For Cohort 1: prior multitargeted VEGFR TKI or systemic therapy allowed
- For Cohort 2: no prior multitargeted VEGFR TKI therapy; prior systemic chemotherapy allowed
- Age 18 years or older
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- Able and willing to swallow oral capsules or tablets
- At least one measurable lesion by RECIST v1.1
- Adequate organ and marrow function within 14 days before registration
- Baseline proteinuria limits for Cohort 2
- Treated brain or CNS metastases allowed if stable
- Negative pregnancy test for females of childbearing potential
- Use of contraception from screening through 90 days post-treatment
- Prior or concurrent malignancy allowed if not interfering with study
- Recovery from prior chemotherapy effects with required washout period
You will not qualify if you...
- Untreated or symptomatic CNS metastases or carcinomatous meningitis
- Major surgery within 14 days before study registration
- Serious or uncontrolled preexisting medical conditions that may interfere with study participation
- Gastrointestinal function impairment affecting drug absorption
- Active systemic bacterial, fungal, or certain viral infections
- Personal history of specific cardiac conditions such as syncope of cardiovascular cause or ventricular arrhythmia
- Pregnant or breastfeeding women
- Not recovered fully from radiotherapy effects; required washout period
- Use of anticoagulants requiring INR monitoring
- Participation in another experimental treatment study within 30 days or 5 half-lives
- Corrected QTcF above specified limits for males and females at screening
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - Up to 2 years or until disease progression, therapy intolerance, or withdrawal
Participants receive the study drugs CB-103 combined with either Abemaciclib or Lenvatinib in 28-day cycles. CB-103 is taken orally twice daily on five consecutive days followed by two days off each week. Abemaciclib or Lenvatinib is taken according to the assigned cohort. Treatment continues until disease progression, therapy intolerance, or participant withdrawal.
Visits occur throughout treatment cycles for dosing and safety monitoring
Duration - Within 30 days after last treatment
Participants have an End of Treatment visit within 30 days after their last dose of study treatment to assess health status and any ongoing effects.
1 visit (in-person)
Trial Site Locations
Total: 1 location
1
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02215
Actively Recruiting
Research Team
G
Glenn Hanna, MD
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
4
Similar Trials
Frequently Asked Questions
Have more questions? Get in touch with our team for quick support
Not the Right Trial for You?
Explore thousands of other clinical trials that might be a better match.
Sign up to get personalized trial recommendations delivered to your inbox.
Already have an account? Log in here