Abemaciclib Plus Ramucirumab for Esophageal/Gastroesophageal Junction Ca

June 4, 2021 updated by: Baylor Research Institute

Phase I/II Study of Abemaciclib + Ramucirumab in Metastatic Esophageal/Gastroesophageal Junction Carcinomas

CDK4/6 and Cyclin D1 are significantly expressed in approximately 80% of esophageal and gastroesophageal junction tumors suggesting that CDK4/6 inhibition may be a successful strategy in these chemotherapy and immunotherapy resistant diseases.

Study Overview

Detailed Description

This is a multicenter, open label, phase I/II safety study that will enroll 30 subjects with metastatic esophageal and gastroesophageal junction adenocarcinomas post first line systemic chemotherapy. Subjects will be treated with oral Abemaciclib 150 mg PO daily bid given with ramucirumab 8mg/kg every 2 weeks iv until evidence of disease progression or unacceptable toxicities.

A total of 30 subjects will be enrolled. The primary goal is to describe the safety profile of Abemaciclib in combination with Ramucirumab among all enrolled subjects.

If grade 3 or higher treatment-related adverse events occur in 20 subjects, the upper bound of 95% Wilson confidence interval for the adverse event rate would be below 81% (16.7% - 47.9%).

The safety analysis will be performed in all treated subjects. Adverse event data will be listed individually and graded according to the National Cancer Institute Common Terminology Criteria, version 4.03.

Summary statistics will include counts and proportions as well as rates with 95% confidence intervals. Toxicities will be reported as a tabulated table by type and grade.

Objective response rate is defined as the percentage of subjects who achieve an objective response by RECIST1.1 criteria (i.e. Complete response or Partial Response) to Abemaciclib in combination with Ramucirumab. We will estimate the objective response rate, along with the Wilson 95% confidence interval, for the population of subjects.

Overall survival will be defined as the time from study enrollment to death. This will be summarized using a Kaplan-Meier curve.

The proportion of subjects with grade 4 or higher treatment-related adverse events will be monitored continuously throughout the trial using a Bayesian stopping guideline. A Beta (1, 19) prior, representing a toxicity rate of 5%, slightly lower than the expected rate of 6%, was used in the development of our guidelines. The therapy will be re-evaluated if the posterior probability that the toxicity rate exceeds 10% is greater than 75%. Table 3 summarizes the stopping boundaries starting with the initial cohort of 3 subjects through the maximum sample size of 30 subjects.

The probability of triggering the stopping guidelines was assessed for a range of possible toxicity rates using simulations with 5000 replicates. The probability of stopping to re-evaluate was 1% if the true proportion with an unacceptable toxicity was 5%. In comparison, the probability of stopping early was 99.6% if the true proportion with an unacceptable toxicity was 40%

Study Type

Interventional

Enrollment (Anticipated)

30

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

    • Texas
      • Dallas, Texas, United States, 75246
        • Baylor University Medical Center, Charles A Sammons Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Subjects must meet all eligibility criteria. The key inclusion and exclusion criteria are as follows:

Key Inclusion Criteria:

  • All subjects must have metastatic esophageal or gastroesophageal junction carcinomas (adenocarcinoma only)
  • ECOG performance status of 0 or 1
  • Tumor tissue must be available for correlative studies - Either a formalin fixed paraffin block or a minimum of ten 5-micron tissue section's (slides) of tumor biopsy sample must be available for biomarker evaluation.
  • Patients must have received at least one prior line of standard systemic therapy for recurrent or Stage IV disease, and that patients with HER2 overexpression have received an anti-HER2 drug.

Key Exclusion Criteria:

  • Squamous cell carcinomas
  • Mixed histology with small cell component

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Abemaciclib plus Ramucirumab
Abemaciclib 150mg dose administered orally twice daily every day plus Ramucirumab dose 8mg/kg iv every 2 weeks until evidence of disease
150mg dose administered orally twice daily every day
8mg/kg iv every 2 weeks until evidence of disease

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
To describe the safety profile of Abemaciclib + Ramucirumab as assessed according to Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0).
Time Frame: 24 months
24 months

Secondary Outcome Measures

Outcome Measure
Time Frame
To assess objective response rate
Time Frame: 24 months
24 months
To assess progression free survival
Time Frame: 24 months
24 months
To assess overall survival
Time Frame: 24 months
24 months
To determine the rate of stable disease at 3 months post targeted therapy
Time Frame: 24 months
24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Ronan Kelly, MD, Charles A Sammons Cancer Center/Texas Oncology

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

June 1, 2021

Primary Completion (Anticipated)

June 1, 2024

Study Completion (Anticipated)

June 1, 2024

Study Registration Dates

First Submitted

June 1, 2021

First Submitted That Met QC Criteria

June 4, 2021

First Posted (Actual)

June 10, 2021

Study Record Updates

Last Update Posted (Actual)

June 10, 2021

Last Update Submitted That Met QC Criteria

June 4, 2021

Last Verified

June 1, 2021

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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