Trastuzumab Deruxtecan and Lovastatin in HER2-low and Ultralow Advanced or Metastatic Breast Cancer
Trial statusNot yet recruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorWashington University School of Medicine
About this trial
The purpose of this study is to evaluate use of lovastatin, a drug that may lower CAV-1 levels, in order to increase HER2 expression on cells and enhance the uptake and efficacy of trastuzumab deruxtecan (T-DXd) in HER2-low and ultralow advanced metastatic breast cancer. Trastuzumab deruxtecan (T-DXd) is an FDA approved antibody drug conjugate for HER2-low and ultralow breast cancer and lovastatin is a cholesterol lowering agent.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Histologically or cytologically confirmed HER2 low (IHC 1+ or 2+ with negative in-situ hybridization) or ultralow (IHC 0 with incomplete/faint membrane staining in >0 but ≤10% of tumor cells) breast cancer. Patients may be advanced/unresectable or metastatic.
Patients must have received no more than 1 prior line of chemotherapy (e.g. capecitabine). There is no limit on the prior number of endocrine-based therapies for patients with hormone-receptor positivity.
Measurable disease per RECIST 1.1.
At least 18 years of age.
Disqualifiers
Prior treatment with T-DXd or other topoisomerase I ADC including sacituzumab govitecan, datopotamab deruxtecan, or investigational ADCs with topoisomerase I payloads.
Prior statin use within 7 days prior to C1D-1.
Patients with unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to grade ≤1 or baseline. Participants with chronic grade 2 toxicities may be eligible per the discretion of the Investigator after consultation with the Study PI or designee (e.g., grade 2 chemotherapy-induced neuropathy).
Prior or concurrent malignancy whose natural history has the potential to interfere with the safety or efficacy assessment of the investigational regimen. Patients with prior or concurrent malignancy that does NOT meet that definition are eligible for this trial
Trial design
Design model
Sequential
Treatments tested in this trial
Trastuzumab deruxtecan
DrugStandard of care trastuzumab deruxtecan is administered at a starting dose of 5.4 mg/kg intravenously every 3 weeks according to package guidelines. The first infusion is administered over 90 minutes, and subsequent infusions may be administered over 30 minutes if prior infusions were well tolerated.
Lovastatin
DrugLovastatin is provided in 10 mg and 20mg tablets for oral administration. It will be taken approximately 12 hours and 10 minutes before each T-DXd cycle.
Treatment groups
60 Participants
are divided into 2 treatment groupsGroup A: Safety Lead In: Trastuzumab Deruxtecan (T-DXd) + LovastatinExperimental treatment 2 interventions
Group B: Standard dose: T-DXd + LovastatinExperimental treatment 2 interventions
Trial outcomes
Primary outcomes
1
Objective Response Rate (ORR)
ORR is defined as the proportion of patients who achieve complete response (CR) or partial response (PR) according to RECIST v1.1. CR is defined as disappearance of all target lesions. Disappearance of all non-target lesions and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Time frame
Start of treatment through end of treatment (estimated total time 12 months)Secondary outcomes
1
Progression Free Survival (PFS)
PFS is defined from treatment start date to date of progression or date of death due to any cause or date of last follow up, whichever is earlier. PFS will be analyzed by the Kaplan-Meier method. Progressive disease (PD) is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).
Time frame
Start of treatment to date of progression, death, or date of last follow up whichever is earlier (total estimated time to be 24 months)2
Overall Survival (OS)
OS is defined from start of treatment to date of death due to any cause or last date of follow up. OS will be analyzed by the Kaplan-Meier method.
Time frame
Start of treatment to date of progression, death, or date of last follow up (total estimated time to be 24 months)3
Safety lead-in only: Rate of unacceptable toxicities
Unacceptable toxicities are assessed according to CTCAE v6.0 and specified in study protocol.
Time frame
Start of treatment to completion of Cycle 2 (each cycle is 3 weeks in length, estimated total time 6 weeks)4
Number and type of adverse events (AEs)
AEs assessed according to CTCAE v6.0.
Time frame
Start of treatment through 30 days post last dose of either study treatment, whichever is later (estimated total time 13 months)Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Washington University School of Medicine
Lead sponsor
National Cancer Institute (NCI)
Collaborator
Source ClinicalTrials.gov
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