Patients With HER2-low Advanced Breast Cancer Treated With T-DXd, Patients With HER2-positive Advanced Breast Cancer Treated With T-DXd
Conditions
Keywords
HER2-positive, HER2-low, advanced breast cancer, T-DXd, NEPA, netupitant/palonosetron
Brief summary
This clinical trial is a prospective, observational, multicenter cohort study evaluating the efficacy and safety of NEPA (netupitant/palonosetron) in patients with HER2-positive or HER2-low advanced breast cancer treated with T-DXd
Detailed description
The observation period of this study is until the discontinuation after administration of T-Dxd or until 8 Cycle. * Acute phase: 0 -24 hours after T-DXd administration * Delayed phase: \>24-120 hours after T-DXd administration * Overall phase: 0-120 hours after T-DXd administration * Long-delayed phase: \>120-504 hours * Extended overall phase: 0-504 hours Primary objectives: to evaluate the efficacy and safety of NEPA for CINV prevention in advanced breast cancer patients receiving at least 2 cycles of T-DXd across all defined assessment periods (acute, delayed, overall, long-delayed, and extended overall phases).
Interventions
None listed
Sponsors
Helsinn Healthcare SA
Yeon Hee Park
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age \>19 years 2. Histologically confirmed breast cancer with metastatic or locally advanced breast cancer not amenable to definitive surgery, with or without measurable disease 3. Stage IV breast cancer at initial diagnosis (de novo) or progression at distant metastatic sites following curative surgery 4. HER2-positive breast cancer (HER2 IHC 3+ or IHC 2+/ISH-positive) or HER2-low breast cancer (HER2 IHC 2+/ISH-negative or HER2 IHC 1+), as defined by the ASCO/CAP guidelines 5. ECOG performance status 0-2 6. Patients who are scheduled to initiate their first cycle of T-DXd therapy 7. Patients who are scheduled to receive netupitant/palonosetron (NEPA) for the prevention of acute and delayed CINV according to the approved indications and dosage instructions 8. Patients who agree to use highly effective contraception methods or not of childbearing potential. Highly effective contraception methods include: A. Total abstinence (when this is in line with the preferred and usual lifestyle of the subject). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. B. Total hysterectomy (surgical removal of the uterus and cervix) or tubal ligation (getting your tubes tied) at least six weeks before taking study treatment. C. Male sterilization (at least 6 months prior to screening). For female subjects on the study, the vasectomized male partner should be the sole partner for that subject. D. Combination of the following: I. Placement of an intrauterine device (IUD) or intrauterine system (IUS) II. Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository 9. Written informed consent
Exclusion criteria
1. Patients who experienced nausea and/or vomiting within 7 days prior to the first cycle of T-DXd treatment 2. Leptomeningeal metastasis and/or brain metastasis 3. Patients with hypersensitivity to any components of the drug or 5-HT3 receptor antagonists. 4. Pregnant women or those suspected of being pregnant, as well as breastfeeding mothers. 5. Any illness or condition that, in the opinion of the Investigator, may pose unwarranted risks in administering T-DXd or NEPA to the patient. 6. Patients requiring treatment with steroids, antiemetics, benzodiazepines, antipsychotics, or other contraindicated drugs, including but not limited to pimozide, terfenadine, astemizole, cisapride, rifampin, carbamazepine, phenytoin, ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, fluvoxamine, SSRIs, SNRIs, ritonavir, or nelfinavir.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete response (CR: no emesis and no rescue medication) | At the end of first Cycle 2 of T-DXd (each cycle is 28 days), assessed up to 6 weeks | CR during the long-delayed phase(\>120-504 hours) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete response (CR: no emesis and no rescue medication) | At the end of first Cycle 2 of T-DXd (each cycle is 28 days), assessed up to 6 weeks | CR during the acute phase (0-24 hours), delayed phase (\>24-120 hours), overall phase (0-120 hours), extended overall phase (0-504 hours) |
| Complete control (CC: no emesis, no rescue medication and no or mild nausea) | At the end of first Cycle 2 of T-DXd (each cycle is 28 days), assessed up to 6 weeks | CC during the acute phase (0-24 hours), delayed phase (\>24-120 hours), overall phase (0-120 hours), long-delayed phase (\>120-504 hours), and extended overall phase (0-504 hours) |
| Total control (TC: no emesis, no rescue medication and no nausea) | At the end of first Cycle 2 of T-DXd (each cycle is 28 day), assessed up to 6 weeks | TC during the acute phase (0-24 hours), delayed phase (\>24-120 hours), overall phase (0-120 hours), long-delayed phase (\>120-504 hours), and extended overall phase (0-504 hours) |
| No significant nausea (NSN: defined as no or mild nausea) | At the end of first Cycle 2 of T-DXd (each cycle is 28 day), assessed up to 6 weeks | NSN during the acute phase (0-24 hours), delayed phase (\>24-120 hours), overall phase (0-120 hours), long-delayed phase (\>120-504 hours), and extended overall phase (0-504 hours |
| No nausea | At the end of first Cycle 2 of T-DXd (each cycle is 28 day), assessed up to 6 weeks | No nausea during the acute phase (0-24 hours), delayed phase (\>24-120 hours), overall phase (0-120 hours), long-delayed phase (\>120-504 hours), and extended overall phase (0-504 hours) |
| CR rate | At the end of first Cycle 2 of T-DXd (each cycle is 28 days), assessed up to 6 weeks | Daily CR rate |
| NSN rate | At the end of first Cycle 2 of T-DXd (each cycle is 28 days), assessed up to 6 weeks | Daily NSN rate |
| no nausea rate | At the end of first Cycle 2 of T-DXd (each cycle is 28 days), assessed up to 6 weeks | Daily no nausea rate |
| Proportion of patients who receive rescue medications | At the end of first Cycle 2 of T-DXd (each cycle is 28 days), assessed up to 6 weeks | Proportion of patients who receive rescue medications |
| Proportion of patients undergoing T-DXd dose delay | At the end of first documented progression or first Cycle 8 of T-DXd (each cycle is 28 days), assessed up to 24 weeks | Proportion of patients undergoing T-DXd dose delay due to nausea and/or vomiting |
| Proportion of patients requiring permanent discontinuation | At the end of first documented progression or first Cycle 8 of T-DXd (each cycle is 28 days), assessed up to 24 weeks | Proportion of patients requiring permanent discontinuation of T-DXd due to nausea and/or vomiting |
| Health-related quality of life (EQ-5D-5L) | At the end of first documented progression or first Cycle 8 of T-DXd (each cycle is 28 days), assessed up to 24 weeks | 1. Range of EQ-5D index Minimum-Maximum Range: approx.-0.28 to -0/17 \ 1,000 2. Range of EQ VASMinimum-Maximum Range: 0\ 100 \*The higher to score, the better the health status. |
| FACIT Fatigue | At the end of first documented progression or first Cycle 8 of T-DXd (each cycle is 28 days), assessed up to 24 weeks | Proportion of patients experiencing fatigue and severity of fatigue (FACIT Fatigue) (1) Range of FACIT Fatigue scale Minimum-Maximum Range 0\ 52 \*Higher score indicate less fatigue and better health status. |
| CTCAE v5.0 | At the end of first documented progression or first Cycle 8 of T-DXd (each cycle is 28 days), assessed up to 24 weeks | Safety evaluated according to CTCAE v5.0, higher scores mean a worse outcome |
| Daily rescue medication rate | At the end of first Cycle 2 of T-DXd (each cycle is 28 days), assessed up to 6 weeks | Daily rescue medication rate |
| Duration of rescue medication | At the end of first Cycle 2 of T-DXd (each cycle is 28 days), assessed up to 6 weeks | Duration of rescue medication |
Countries
South Korea
Outcome results
None listed