Multiorgan Metabolic Imaging Response Assessment of Abemaciclib

NCT03339843 | Completed Phase 2

• 1 other identifier: IJB-MULTI-MIME-A-2017
• Study Type: interventional
• Target: 85
• Locations: 2 countries
• Sites: 11

Brief Summary

Open-label, phase II, basket trial. This trial is a screening program for abemaciclib efficacy in multiple platinum-resistant tumour types by using metabolic imaging (PERCIST) and RECIST v1.1 criteria. Based on the rate of FDG-avidity and the absence of deactivation of the Rb gene function in more than 95% of cases, we propose to define 5 tumour types of interest in a preliminary stage:

1. 1.Platinum-refractory esophageal adenocarcinoma (ADC)
2. 2.Platinum-refractory esophageal squamous cell carcinoma (SCC)
3. 3.Platinum-refractory cholangiocarcinoma
4. 4.Platinum-refractory and progressive after immunotherapy urothelial cancer
5. 5.Platinum-refractory endometrial cancer

Conditions

Esophageal Adenocarcinoma; Esophagus SCC; Cholangiocarcinoma; Urothelial/Bladder Cancer, Nos; Endometrial Cancer

Keywords

cancer

Outcome Measures

Primary Outcomes (2)

• Evaluate the anti-tumour activity of abemaciclib in the five tumour types studied in this trial using FDG-PET/CT during the first cycle of therapy (early FDG- PET/CT).

  Therapy success rate defined as: PERCIST 15%-assessed Metabolic Response at early FDG-PET/CT (D12-D16)

  2 months

• Evaluate the anti-tumour activity of abemaciclib in the five tumour types studied in this trial using RECISTv1.1 after 2 cycles of therapy as a screening tool.

  Therapy success rate defined as: RECISTv1.1-assessed Disease Control (DC) after 2 treatment cycles (CR or PR or SD)

  2 Months

Secondary Outcomes (6)

• Evaluate Progression-free survival (PFS define as the time from treatment start until disease progression or death) at 24 weeks from treatment start

  6 months

• Evaluate Overall Survival (OS defined as the time from treatment start until death) at 24 weeks from treatment start

  6 months

• To evaluate median progression-free survival (PFS)

  42 months

• Evaluate median overall survival (OS)

  42 months

• To evaluate toxicity profile

  6 months

Study Arms (1)

Abemaciclib

EXPERIMENTAL

This study contains 2 stages; during the 1st stage, a maximum of 17 patients will be enrolled in each tumour type cohort. After 13 evaluable patients have been enrolled, an interim analysis will be performed. If 3 or more patients are seen to have experienced a treatment success, then the cohort will pass into the 2nd stage in which a maximum of 20 more patients are enrolled. If 2 or less patients are seen to have experienced a treatment success, then that cohort will be closed and will not proceed into the 2nd stage. Subjects will receive 200 mg of abemaciclib orally, twice a day, during cycles of 28 days each. The subject will undergo: A baseline FDG-PET/CT and a baseline CT scan and A blinded early FDG-PET/CT at D14 +/- 2 days of study treatment. A treatment success is defined as a patient who has metabolic response according to PERCIST with a response cut off set at 15% at the early FDG-PET/CT and a morphological disease control after 2 cycles measured by RECIST v1.1.

Drug: Abemaciclib

Interventions

Abemaciclib DRUG

Subjects will receive 200 mg of abemaciclib orally, two times a day, during cycles of 28 days each. An early FDG-PET/CT will be performed at cycle 1 day 14 to search for any new lesions.

Also known as: FDG-PET/CT

Abemaciclib

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years old
• Female or male
• ECOG performance status ≤ 1
• Life expectancy of greater than 12 weeks
• Must have histologically confirmed cancer corresponding to the predefined tumour subtypes (esophageal adenocarcinoma, esophageal squamous cell carcinoma, cholangiocarcinoma, urothelial cancer (progressive after immunotherapy), endometrial cancer) and metastatic or non-resectable and refractory to standard platinum regimens (and progressive after immunotherapy for the urothelial cancer).
• Presence of at least one metabolically measurable tumour lesion on FDG-PET/CT, according to PERCIST. If previously irradiated, must have been more than 2 months before the baseline FDG PET/CT.
• Measurable disease according to RECIST v 1.1
• Serum pregnancy test (for subjects of childbearing potential) negative
• Women of childbearing potential must agree to the use a highly effective method of contraception prior to study entry, during the course of the study and at least 3 months after the last administration of study treatment.
• Men with childbearing potential partner must agree to use condom during the course of this study and for at least 3 months after the last administration of the study treatment.
• Adequate coagulation: International Normalized Ratio (INR) ≤ 1.5 x ULN unless subject is receiving anticoagulant therapy as long as INR and activated partial thromboplastin time \[aPTT\] are within therapeutic range of intended use of anticoagulants
• Adequate bone marrow function as defined below:
• Hemoglobin ≥ 10 g/dL
• Absolute neutrophil count ≥ 1500/µL or 1.5x109/L
• Platelets ≥ 100000/µL or 100x109/L

You may not qualify if:

• Subjects meeting one of the following criteria are not eligible for this studyParticipants who have had chemotherapy, radiotherapy, immunotherapy, or targeted therapy within 3 weeks prior study enrolment
• Participants receiving concomitantly any other experimental agents
• Patients who have received prior therapy with other CDK4/6 inhibitors
• Subjects with known brain metastasis; unless the metastasis are asymptomatic and have been stable since at least 2 months prior to treatment start.
• Patient with meningeal carcinomatosis
• Have had major surgery within 28 days prior to the start of the treatment to allow for post-operative healing of the surgical wound
• History of allergic reactions attributed to compounds of similar chemical or biologic composition
• Bleeding diathesis, thromboembolic event, history of cardiovascular ischemic disease or cerebrovascular incident within the last six months
• Uncontrolled concurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia
• Substance abuse, psychiatric illness/social situations, any psychological, familial, sociological, geographical condition, significant medical or surgical condition currently uncontrolled by treatment that would limit compliance with study requirements or interfere with the patient's ability to understand informed consent and participation in the study
• Pregnant and/or lactating women
• Uncontrolled Diabetes
• Known history of HIV infection, or active hepatitis B or C requiring treatment with anti-viral therapy
• Have received recent (within 28 days prior the enrolment) yellow fever vaccination
• Individuals with a history of a different malignancy are ineligible except for the following circumstances. Individuals with a history of other malignancies are eligible if they have been disease-free and are deemed by the investigator to be at low risk for recurrence of that malignancy.

Sponsors & Collaborators

• Jules Bordet Institute: lead
• Eli Lilly and Company: collaborator

Study Sites (11)

Universitair Ziekenhuis

Antwerp, Belgium

Location

Institut Jules Bordet

Brussels, 1000, Belgium

Location

Algemeen Ziekenhuis Groeninge

Kortrijk, 8500, Belgium

Location

CHC Saint-Joseph

Liège, 4000, Belgium

Location

CHU Ambroise Paré

Mons, 7000, Belgium

Location

CHU UCL Namur Sainte-Elisabeth

Namur, 5000, Belgium

Location

Centre Oscar Lambret

Lille, 59000, France

Location

Institut Paoli-Calmettes

Marseille, 13009, France

Location

Centre Henri Becquerel

Rouen, 76038, France

Location

Hôpital universitaire de Strasbourg - ICANS

Strasbourg, 67000, France

Location

IUCT Oncopole - Institut Claudius Regaud

Toulouse, 31059, France

Location

MeSH Terms

Conditions

Adenocarcinoma Of Esophagus; Esophageal Squamous Cell Carcinoma; Cholangiocarcinoma; Urologic Neoplasms; Endometrial Neoplasms; Neoplasms

Interventions

abemaciclib

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Squamous Cell; Esophageal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Adenocarcinoma; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urologic Diseases; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Diseases; Genital Diseases, Female; Genital Diseases

Study Officials

• Laura Polastro, MD

  Jules Bordet Institute

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a two step, open-label, basket trial looking at 5 different tumour types.

Study Record Dates

• First Submitted: October 5, 2017
• First Posted: November 13, 2017
• Study Start: December 19, 2018
• Primary Completion: November 12, 2021
• Study Completion: December 20, 2023
• Last Updated: March 15, 2024

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

BE (6); FR (5)