Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Carcinoma

Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Fulvestrant

Estrogens

Antineoplastic Agents, Hormonal

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormones

Hormone Antagonists

Postmenopausal patients with estrogen receptor positive metastatic breast cancer harboring NF1 loss of function or another alteration of the MAPK pathway.

Part 1: safety run-in (confirmation of the RP2D for mirdametinib in combination with the standard recommended dose of fulvestrant). This part may include the mirdametinib dose de-escalation according to the 3+3 design if necessary

Postmenopausal patients with estrogen receptor positive metastatic breast cancer harboring NF1 loss of function or another alteration of the MAPK pathway.

Part 2: dose expansion cohorts where the mirdametinib RP2D will be administered in combination with the standard recommended dose of fulvestrant

Adult patients with advanced solid cancers driven by the alteration of the MAPK pathway

Part 1: mirdametinib dose escalation to MTD or RP2D according to the 3+3 design

Adult patients with advanced solid cancers driven by the alteration of the MAPK pathway

Part 2: dose expansion cohorts

Dose Level -2INT: 2mg PO BID, 3 weeks on/1 week off Dose Level -2: 2mg PO BID given continuously Dose Level -1INT: 3mg PO BID, 3 weeks on/1 week off Dose Level -1: 3mg PO BID given continuously Dose Level 1: 4mg PO BID given continuously Dose Level 2: 6mg PO BID given continuously Dose Level 3: 8mg PO BID given continuously

Mirdametinib

The starting dose of mirdametinib in combination with fulvestrant in each Dose Level will be as follows:

* Dose Level 1: mirdametinib 4 mg BID PO + fulvestrant
* (Only to be triggered pending DLTs on higher Dose Levels as described below)

  * Dose Level -2: mirdametinib 2 mg BID PO continuous + fulvestrant, and Dose Level -2INT: mirdametinib 2 mg BID PO on 3 weeks on, 1 week off + fulvestrant

Ezra Rosen, MD, PhD

The purpose of this study to find out whether mirdametinib is a safe treatment for people with advanced solid tumor cancer that has certain mutations. Researchers will look at whether mirdametinib on its own or in combination with the drug fulvestrant is a safe treatment that causes few or mild side effects in people with advanced solid tumor cancer.

A Study of Mirdametinib on Its Own or in Combination With Fulvestrant in People With Solid Tumor Cancer

A Phase 1b / 2a, Open-label Platform Study to Evaluate Mirdametinib as Monotherapy or in Combination With Other Anticancer Agents in Patients With Advanced Solid Cancers Harboring MAPK-activating Mutations

Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

DLT Evaluable Population consists of patients who receive at least 80% of planned total doses of mirdametinib in cycle 1 (in Arm 1 only, also both doses of fulvestrant) and are observed within 28 days following the first dose of mirdametinib or patients who experience a DLT.

Spots Global Cancer Trial Database for estrogen receptor positive metastatic breast cancer