Health TrialsbyHealthPanel

Testing the Combination of the Anticancer Drugs ZEN003694 and Binimetinib in Patients With Advanced/Metastatic or Unresectable Solid Tumors With RAS Alterations and Triple Negative Breast Cancer

ConditionsAdvanced Malignant Solid NeoplasmMetastatic Malignant Solid NeoplasmRefractory Malignant Solid NeoplasmTriple-Negative Breast CarcinomaUnresectable Malignant Solid Neoplasm
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorNational Cancer Institute (NCI)

About this trial

This phase I trial tests the safety, side effects, and best dose of ZEN003694 in combination with binimetinib in treating patients with solid tumors that carry RAS alterations and that have spread to other places in the body (advanced/metastatic) or cannot be removed by surgery (unresectable). ZEN003694 is an oral medication with potential anticancer activity. It is an inhibitor of a family of proteins called bromodomain and extra-terminal (BET) which play important role during development and cellular growth. ZEN003694 may stop the growth of tumor cells that produce BET. Binimetinib is in a class of medications called kinase inhibitors. It works by blocking the action proteins called MEK1 and MEK2, that signal cancer cells to multiply. It may help keep cancer cells from growing and spreading. There is pre-clinical evidence that using ZEN003694 and binimetinib together may shrink or stabilize cancers studied in this trial. There are two parts of this study; dose escalation and dose expansion. In the dose escalation part of this study, different people will get different doses of the study drugs ZEN003694 and binimetinib. In the dose expansion part of this study, the highest dose with manageable side effects will be given to additional people. This will help to understand the side effects that may happen with this drug combination.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Patients must have histologically confirmed advanced/metastatic or unresectable solid tumor that is refractory to standard therapy or has relapsed after standard therapy

For Part 1 and 2 -

Triple negative breast cancer (TNBC) (estrogen receptor =< 1%, progesterone receptor =< 1%, human epidermal growth factor receptor 2 0-1+ or non-amplified)

Solid tumor with genomic alteration(s) activating RAS signaling including activating KRAS, NRAS, HRAS, or BRAF mutations, inactivating NF1 mutations, or BRAF fusions

Disqualifiers

Patients who have not recovered from adverse events (AEs) due to prior anticancer therapy (i.e., have residual toxicities > Grade 1) with the exception of alopecia, peripheral neuropathy, and endocrinopathy managed with replacement therapy before the initiation of study treatment

Patients who are receiving any other investigational agents

Breast cancer patients with a prior history of hormone receptor positivity will not be eligible

Patients with known PI3K pathway activating genomic alterations including inactivating mutations/deletions in PTEN and PIK3R1, amplifications in PIK3CA, and activating mutations in PIK3CA, Akt, or mTOR will not be eligible

Trial design

Design model

Single group

Treatments tested in this trial

  • BET Bromodomain Inhibitor ZEN-3694

    Drug

    Given PO

  • Binimetinib

    Drug

    Given PO

  • Biopsy Procedure

    Procedure/Surgery

    Undergo biopsy

  • Biospecimen Collection

    Procedure/Surgery

    Undergo collection of blood samples

  • Computed Tomography

    Procedure/Surgery

    Undergo CT

  • Magnetic Resonance Imaging

    Procedure/Surgery

    Undergo MRI

Treatment groups

42 Participants
are divided into 1 treatment group
Group A: Treatment (ZEN-3694, binimetinib)Experimental treatment 6 interventions

Trial outcomes

Primary outcomes

1

Incidence of dose limiting toxicities (Part 1 [Dose Escalation])

Defined as the incidence of clinically significant adverse events (AEs) or abnormal laboratory values thought to be at least possibly related to the study treatment occurring during the first cycle.

Time frame
Up to 28 days from treatment start date
2

Incidence of AEs (Part 2 [Dose Expansion])

Including but not limited to treatment-emergent AEs, severe adverse events, deaths, and clinical laboratory abnormalities, as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0.

Time frame
Up to 30 days after last treatment dose

Secondary outcomes

1

Incidence of AEs (Part 1 [Dose Escalation])

Toxicity will be graded according to the NCI CTCAE v5.0. Toxicity will be summarized by grade and type using descriptive statistics, including frequency and 95% confidence interval.

Time frame
Up to 30 days after last treatment dose
2

Pharmacokinetic (PK) parameters (Part 1 [Dose Escalation])

PK parameters will be estimated using non-compartmental method(s) and correlated with pharmacodynamic endpoints using non-parametric statistics.

Time frame
Days 2, 8, 15, and 16 of cycle 1
3

Overall response rate (ORR)

Defined as the percentage of participants who have a partial or complete response to the treatment. Descriptive statistics will be used to summarize ORR.

Time frame
Up to 2 years from treatment start date
4

Disease control rate (DCR)

Defined as the percentage of participants that have achieved complete response, partial response or stable disease after treatment. Descriptive statistics will be used to summarize DCR.

Time frame
Up to 4 months from treatment start date

Other outcomes

Sponsors and contacts

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

National Cancer Institute (NCI)

Lead sponsor

Source ClinicalTrials.gov
Apply now