Trial Title:
Zunsemetinib in Combination With Capecitabine in Patients With Hormone Receptor-Positive and HER2-Negative Metastatic Breast Cancer With Bone Metastasis
NCT ID:
NCT06374459
Condition:
Hormone Receptor Positive HER-2 Negative Metastatic Breast Cancer
Conditions: Official terms:
Breast Neoplasms
Neoplasm Metastasis
Zoledronic Acid
Denosumab
Capecitabine
Conditions: Keywords:
Zunsemetinib
ATI-450
MK-2
Bone metastasis
Breast Cancer
HR-positive/HER2-negative
Capecitabine
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Sequential Assignment
Intervention model description:
The Phase I portion of the study is sequential and patients will not be randomized and
the Phase II portion is parallel and patients will be randomized.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Zumsemetinib
Description:
Patients should take zunsemetinib at approximately the same times every day, with or
without food with 8 oz of water.
Arm group label:
Phase II Arm 2: Zunsemetinib (RP2D-L1) + Capecitabine
Arm group label:
Phase II Arm 3: Zunsemetinib (RP2D-L2) + Capecitabine
Arm group label:
Phase Ib: Zunsemetinib + Capecitabine
Other name:
ATI-450
Intervention type:
Drug
Intervention name:
Capecitabine
Description:
Patients should take capecitabine at approximately the same times every day, within 30
minutes after a meal.
Arm group label:
Phase II Arm 1: Standard of care anti-resorptive + Capecitabine
Arm group label:
Phase II Arm 2: Zunsemetinib (RP2D-L1) + Capecitabine
Arm group label:
Phase II Arm 3: Zunsemetinib (RP2D-L2) + Capecitabine
Arm group label:
Phase Ib: Zunsemetinib + Capecitabine
Intervention type:
Drug
Intervention name:
Zoledronic acid
Description:
Standard of care. Will receive zoledronic acid or denosumab.
Arm group label:
Phase II Arm 1: Standard of care anti-resorptive + Capecitabine
Intervention type:
Drug
Intervention name:
Denosumab
Description:
Standard of care. Will receive zoledronic acid or denosumab.
Arm group label:
Phase II Arm 1: Standard of care anti-resorptive + Capecitabine
Summary:
This is a phase Ib/II study evaluating the safety and efficacy of zunsemetinib (ATI-450)
with capecitabine in patients with hormone receptor-positive and HER2-negative
(HR+/HER2-) metastatic breast cancer (MBC).
Criteria for eligibility:
Criteria:
Inclusion Criteria for both Phase Ib and Phase II:
- Hormone receptor-positive, HER2-negative metastatic breast cancer.
- Measurable or non-measurable but evaluable disease by RECIST v1.1.
- Candidate for capecitabine treatment per physician decision. See below
phase-specific eligibility criteria for further guidance.
- No more than one prior chemotherapy for metastatic disease.
- Patient must have received prior endocrine therapy with CDK4/6 inhibitor.
- If patient is on denosumab or zoledronic acid prior to enrollment, patient must have
been on the regimen for at least 6 months prior to study. However, a washout of 3
weeks is required prior to C1D1.
- At least 18 years of age.
- ECOG performance status 0, 1, or 2
- Life expectancy of at least 12 weeks.
- Adequate bone marrow and organ function as defined below:
- Leukocytes ≥ 3 K/cumm
- Absolute neutrophil count (ANC) ≥ 1.5 K/cumm
- Platelets ≥ 100 K/cumm
- Total bilirubin ≤ 1.5 x IULN (or total bilirubin ≤ 3 mg/dL if patient has known
Gilbert Syndrome)
- AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN
- Creatinine clearance > 60 mL/min by Cockcroft-Gault
- Calcium within normal limits
- Women of childbearing potential and men who are heterosexually active must agree to
use adequate contraception as specified in the protocol. Contraception should
continue for 6 months (for women) or 3 months (for men) after the end of treatment.
Should a woman become pregnant or suspect she is pregnant while participating in
this study, she must inform her treating physician immediately.
- Ability to understand and willingness to sign an IRB approved written informed
consent document.
- Patients must have archival tissue sample available from prior metastatic biopsy. If
no tissue is available, patient may still be able to enroll with PI approval.
Inclusion Criteria for both Phase Ib:
- Presence of bone metastasis is not required.
- Candidate for, or currently on stable doses of capecitabine, defined as
capecitabine: 1000 mg/m^2 BID, 14 days on and 7 days off. A stable dose of
capecitabine is defined as no more than grade 1 AEs related to capecitabine on the
1000 mg/m^2 BID, 14 days on and 7 days off dose for at least 1 cycle. Capecitabine
is not counted as a prior chemotherapy regimen in these patients.
Inclusion Criteria for Phase II:
- Progressive bone metastasis per the most recent tumor imaging studies by RECIST 1.1
or clinical progression (such as worsening bone pain, elevation of tumor marker) per
treating physician.
Exclusion Criteria for both Phase Ib and Phase II:
- Patients may not have received the following investigational or SOC therapies within
the below specified time frames prior to C1D1:
- Radiation therapy within 1 week
- Systemic chemotherapy, including antibody drug conjugates with chemotherapy
payload, within 3 weeks.
- Immunotherapy within 3 weeks
- Oral chemotherapy or molecularly targeted therapy within 5 half-lives of the
agent.
- Endocrine therapies do not have a required washout and may be continued until
C1D1.
- Strong and moderate CYP3A4 and CYP2C8 inhibitors (including grapefruit), strong
and moderate CYP3A and CYP2C8 inducers, and drugs with QT prolonging potential
within 5 half-lives of the agent.
- Untreated brain metastases. Patients with treated brain metastases are eligible if
they show no evidence of progression and are off steroids.
- A history of allergic reactions attributed to compounds of similar chemical or
biologic composition to zunsemetinib or other agents used in the study.
- History of acute, untreated skeletal related events (SRE) or active untreated SRE or
a change or an anticipated change in the SOC anti-resorptive agents after entering
the study.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, or
cardiac arrhythmia.
- Pregnant and/or breastfeeding. Women of childbearing potential must have a negative
pregnancy test within 14 days of C1D1.
- Patients with HIV are eligible unless their CD4+ T-cell counts are < 350 cells/mcL
or they have a history of AIDS-defining opportunistic infection within the 12 months
prior to Cycle 1 Day 1. Concurrent treatment with effective ART according to DHHS
treatment guidelines is recommended.
- Screening resting QTcF above 470 msec.
Exclusion Criteria for Phase Ib:
- Capecitabine within 2 weeks prior to C1D1. Patients may be currently taking
capecitabine, but must not have dosed within 2 weeks prior to C1D1 for study
correlative purposes.
Exclusion Criteria for Phase II:
- Prior capecitabine in the metastatic setting.
- History of other malignancy, unless all treatment was completed and patient had no
evidence of disease within 2 years of C1D1.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
The University of Kansas Cancer Center
Address:
City:
Westwood
Zip:
66205
Country:
United States
Contact:
Last name:
Qamar Khan, M.D.
Phone:
913-588-1227
Investigator:
Last name:
Qamar Khan, M.D.
Email:
Principal Investigator
Facility:
Name:
Mayo Clinic
Address:
City:
Rochester
Zip:
55905
Country:
United States
Contact:
Last name:
Matthew Goetz, M.D.
Phone:
507-284-2511
Email:
Goetz.Matthew@mayo.edu
Investigator:
Last name:
Matthew Goetz, M.D.
Email:
Principal Investigator
Facility:
Name:
Washington University School of Medicine
Address:
City:
Saint Louis
Zip:
63110
Country:
United States
Contact:
Last name:
Cynthia X Ma, M.D., Ph.D.
Phone:
314-362-8903
Email:
cynthiaxma@wustl.edu
Investigator:
Last name:
Cynthia X Ma, M.D., Ph.D.
Email:
Principal Investigator
Investigator:
Last name:
Sheila Stewart, Ph.D.
Email:
Sub-Investigator
Investigator:
Last name:
Roberto Civitelli, M.D.
Email:
Sub-Investigator
Investigator:
Last name:
Jingqin (Rosy) Luo, Ph.D.
Email:
Sub-Investigator
Investigator:
Last name:
Foluso Ademuyiwa, M.D.
Email:
Sub-Investigator
Investigator:
Last name:
Nusayba Bagegni, M.D.
Email:
Sub-Investigator
Investigator:
Last name:
Ron Bose, M.D., Ph.D.
Email:
Sub-Investigator
Investigator:
Last name:
Andrew Davis, M.D.
Email:
Sub-Investigator
Investigator:
Last name:
Ashley Frith, M.D., Ph.D.
Email:
Sub-Investigator
Investigator:
Last name:
Faisal Fa'ak, M.D.
Email:
Sub-Investigator
Investigator:
Last name:
Lindsay Peterson, M.D.
Email:
Sub-Investigator
Investigator:
Last name:
Rama Suresh, M.D.
Email:
Sub-Investigator
Start date:
November 30, 2024
Completion date:
March 31, 2032
Lead sponsor:
Agency:
Washington University School of Medicine
Agency class:
Other
Collaborator:
Agency:
United States Department of Defense
Agency class:
U.S. Fed
Collaborator:
Agency:
Aclaris Therapeutics, Inc.
Agency class:
Industry
Source:
Washington University School of Medicine
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06374459
http://www.siteman.wustl.edu
