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Testing the Safety and Efficacy of the Combination of Two Anti-cancer Drugs, ZEN003694 and Abemaciclib, for Adult and Pediatric Patients (12-17 Years) With Metastatic or Unresectable NUT Carcinoma, Breast Cancer and Other Solid Tumors

ConditionsAnatomic Stage III Breast Cancer AJCC v8Anatomic Stage IV Breast Cancer AJCC v8Metastatic Breast CarcinomaMetastatic Malignant Solid NeoplasmMetastatic NUT CarcinomaUnresectable Breast CarcinomaUnresectable Malignant Solid NeoplasmUnresectable NUT Carcinoma
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age12+
SponsorNational Cancer Institute (NCI)

About this trial

This phase I trial tests the safety, side effects, and best dose of ZEN003694 when given together with abemaciclib in treating patients with NUT carcinoma, breast cancer or other solid tumors that have spread from where it first started (primary site) to other places in the body (metastatic) or cannot be removed by surgery (unresectable). ZEN003694 is an inhibitor of a family of proteins called the bromodomain and extra-terminal (BET). It may prevent the growth of tumor cells that overproduce BET protein. Abemaciclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving ZEN003694 and abemaciclib may help shrink or stabilize cancer in patients with NUT carcinoma, breast cancer or other solid tumors.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Participants must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective

Dose Escalation Cohort Only: Participants must have evaluable disease or measurable disease per RECIST 1.1 criteria

Ectopic expression of NUT protein per World Health Organization (WHO) criteria as determined by immunohistochemistry (IHC) testing, OR

Detection of the NUT gene translocation as determined by fluorescence in situ hybridization (FISH) testing, OR

Disqualifiers

Participants who have had cytotoxic chemotherapy, immunotherapy, or other investigational therapy within 2 weeks prior to entering the study. There is a two-week required washout period for previous BET inhibitor therapy

Participants who have had radiotherapy within at least 2 weeks prior to entering the study. Stereotactic radiosurgery (SRS) within 1 week prior to entering the study will be allowed

Participants who have had major surgery within 3 weeks prior to entering the study

Participants who have received tyrosine kinase inhibitors (TKIs) or small molecules within 5 half-lives or 1 week (whichever is shorter) of study entry

Trial design

Design model

Single group

Treatments tested in this trial

  • Abemaciclib

    Drug

    Given PO

  • BET Bromodomain Inhibitor ZEN-3694

    Drug

    Given PO

  • Biopsy Procedure

    Procedure/Surgery

    Undergo biopsy

  • Biospecimen Collection

    Procedure/Surgery

    Undergo blood sample collection

  • Diagnostic Imaging Testing

    Procedure/Surgery

    Undergo imaging evaluation

Treatment groups

45 Participants
are divided into 1 treatment group
Group A: Treatment (ZEN003694, abemaciclib)Experimental treatment 5 interventions

Trial outcomes

Primary outcomes

1

Maximum tolerated dose or recommended phase 2 dose (Phase I dose escalation)

The toxicity of the combination will be assessed using Common Terminology Criteria for Adverse Events (CTCAE) version (v). 5.0 criteria.

Time frame
During the first cycle of therapy (28 days)
2

Incidence of adverse events (Phase I dose expansion)

Safety will be reported with descriptive statistics. Toxicity will be graded according to National Cancer Institute CTCAE, v5.0. Toxicities will be summarized by maximum grade and by treatment arm. Incidence rate of each toxicity will be reported with 95% exact confidence intervals.

Time frame
Up to 5 years
3

Overall response rate (Phase I dose expansion)

Will be graded as complete response (CR), partial response (PR), stable disease (SD) and progressive disease.

Time frame
Up to 5 years
4

Clinical benefit rate (CBR) (Phase I dose expansion)

Clinical benefit is defined as CR, PR or SD \>= 24 weeks according to Response Evaluation Criteria in Solid Tumors 1.1. CBR will be reported with 90% exact confidence intervals.

Time frame
Up to 5 years

Secondary outcomes

1

Pharmacokinetics (PK)

Designed the PK sampling to enable simultaneous estimation of individual pharmacokinetic parameters of abemaciclib, ZEN003694, and their respective metabolites using nonlinear mixed effects modeling. Will compare the ratio of observed/historical 90% confidence interval of abemaciclib exposure.

Time frame
Up to 5 years
2

Thymidine kinase (TK)

Will compare exposures of abemaciclib and abemaciclib metabolites to TK activity at cycle 1 day 15 and beyond and also change in TK activity versus clinical outcomes.

Time frame
Up to 5 years

Other outcomes

1

Analysis of ATAC-sequence data

An internal pipeline will be used to perform quality control and data pre-processing. Burrows-Wheeler Aligner will be used for read mapping against the hg19 map using default parameters.

Time frame
Up to 5 years

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

National Cancer Institute (NCI)

Lead sponsor

Source ClinicalTrials.gov
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