Hormone Receptor Positive Breast Adenocarcinoma, Locoregionally Recurrent Hormone-receptor Positive Breast Cancer, Metastatic Hormone Receptor Positive Breast Cancer
Conditions
Keywords
Hormone Receptor Positive Breast Cancer, Endocrine resistant, Radioisotope
Brief summary
A phase 1 imaging study of 68Ga-R10602 in hormone-receptor positive breast cancer.
Detailed description
There are three eligible disease populations for the study. Population 1 are patients with metastatic or locoregionally recurrent, endocrine-resistant, ER+ and/or PR+ breast cancer who have received at least one line of chemotherapy or ADC. Population 2 are patients with ER+ and HER2- locoregional or metastatic non-resectable breast adenocarcinoma with progression on at least one line of prior endocrine therapy in the adjuvant or metastatic setting and starting next line of therapy that will include tamoxifen, fulvestrant, aromatase inhibitor, or elacestrant with or without ovarian suppression. Population 3 are patients with ER+ and/or PR+ and HER2- breast cancer who are ineligible for Population 1 or 2. All disease populations are eligible for both cohorts. Cohort 1 will consist of three dose de-escalating cohorts with four patients each for a total of twelve patients. Once the twelve patients have completed the dose de-escalation, the three dose levels will be evaluated, and additional subjects may be enrolled into Cohort 1 at the single chosen dose. All patients will undergo imaging at a single timepoint and no dosimetry will be performed. In Cohort 2, approximately six to eight patients will receive the single chosen dose followed by imaging at five timepoints and blood dosimetry at seven timepoints.
Interventions
DRUG68Ga-R10602 injection
68Ga-R10602 is a gallium-labeled small molecule radioligand that is designed to localize tumor lesions in hormone receptor positive breast cancer
Sponsors
Radionetics Oncology
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Breast Cancer Eligibility: * Population 1: Pathologically confirmed ER and/or PR positive, locoregionally recurrent or metastatic breast cancer that is refractory to endocrine therapy (progression on at least one line of endocrine therapy and determined by the investigator that Study Participant would not benefit from additional endocrine therapy) who have received at least one line of chemotherapy or antibody drug conjugate in the metastatic setting (recurrence within 6 months of adjuvant chemotherapy counts as one line of therapy). There is no limit on prior number of lines of endocrine therapy. Prior treatment with CDK4/6, AKT, PI3K and/or mTOR inhibitors is permitted. * Population 2: Pathologically confirmed ER positive and HER2 negative locoregional or metastatic breast adenocarcinoma that is not amenable to resection, with progression on at least one line of prior endocrine therapy in the adjuvant or metastatic setting and starting next line of therapy that will include endocrine therapy, such as tamoxifen, fulvestrant, aromatase inhibitor, or elacestrant with or without ovarian suppression. * Population 3: Study Participants with pathologically confirmed, estrogen and/or progesterone receptor (ER and/or PR) positive and HER2 negative breast adenocarcinoma who are ineligible for Population 1 or 2. 2. At least one target or non-target lesion per RECIST 1.1 3. Male or non-pregnant, non-lactating female Study Participant age ≥18 years. Female Study Participant of child-bearing potential and male Study Participant (if sexually active) must agree to use adequate method(s) of effective contraception during their participation in the study. 1. Medically acceptable adequate contraception for sexually active females with child-bearing potential include: 1) surgical sterilization (such as tubal ligation or hysterectomy), 2) approved hormonal contraceptives, 3) barrier method (such as condom or diaphragm) used with a spermicide, or 4) intrauterine device (IUD). 2. Medically acceptable adequate contraception for sexually active males include: 1) surgical sterilization (such as vasectomy), 2) a condom used with a spermicide. 4. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤2. 5. Adequate hepatic function as defined below (within 28 days of dosing with 68Ga R10602): 1. Serum alanine aminotransaminase (ALT)/ aspartate aminotransaminase (AST) ≤3 × upper limit of normal (ULN) or ≤5 × ULN if liver metastases are present, and 2. Serum bilirubin: total ≤1.5 × ULN (unless due to Gilbert's syndrome or hemolysis in which case total ≤3.0 × ULN). 6. Adequate renal function as measured by creatinine clearance calculated by the Cockcroft-Gault formula (≥60 mL/minute), determined within 28 days of dosing with 68Ga-R10602. 7. Able to understand and willing to sign an informed consent form (ICF).
Exclusion criteria
1. Received a radionuclide within a period of less than 10 physical half-lives of the administered radionuclide prior to dosing with 68Ga-R10602. 2. Radiotherapy ≤14 days prior to dosing with 68Ga-R10602. 3. Major surgery ≤21 days prior to dosing with 68Ga-R10602 or has not recovered from adverse effects of such procedure. 4. Severe or unstable medical condition, such as congestive heart failure (New York Heart Association \[NYHA\] Class III or IV), ischemic heart disease, uncontrolled hypertension, uncontrolled diabetes mellitus, as well as an uncontrolled cardiac arrhythmia requiring medication (≥Grade 2, according to NCI-CTCAE Version 5.0), myocardial infarction within 6 months prior to starting Investigational Product, or any other significant or unstable concurrent cardiac illness. Note: Stable chronic atrial fibrillation is allowed. 5. History of cerebrovascular accident within 6 months or that resulted in ongoing neurologic instability. 6. Major active infection requiring antibiotics. 7. Known active human immunodeficiency virus infection or active infection with Hepatitis B or C. 8. Acute illness within 14 days prior to dosing with 68Ga-R10602 unless mild in severity, as assessed by the Investigator. 9. Any other condition that in the opinion of the Investigator would place the Study Participant at an unacceptable risk or cause the Study Participant to be unlikely to fully participate or comply with study procedures.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of adverse events | Day 1 to Day 7 | Number of participants with adverse events as assessed by NCI-CTCAE v5.0, including grade |
| Incidence of Serious Adverse Events | Day 1 to Day 7 | Number of participants with serious adverse events |
| Incidence of Clinically Significant Lab Changes | Day 1 to Day 7 | Number of participants with clinically significant change in clinical laboratory parameters |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number and location of tumors identified by 68Ga-R10602 PET/CT | 1 day | Number of tumors identified by 68Ga-PET/CT per participant |
| Number and location of tumor lesions identified by 68Ga-R10602 PET/CT versus standard of care imaging | 1 day | Number and location of tumor lesions identified by 68Ga-R10602 PET/CT and by standard of care imaging (e.g. contrast enhanced diagnostic CT) and concordance rate between 68Ga-R10602 PET/CT and standard of care images. |
| Image quality | 1 day | Image quality as assessed by a 5-point Likert scale by central review |
| Absorbed dose coefficients and total body effective dose | 1 day | Absorbed dose coefficients (milliGray \[mGy\]/megabecquerel \[MBq\]) in organs. |
| PK parameters | 1 day | PK parameters, including Cmax |
Countries
United States
Outcome results
None listed