رادار التجارب AI | ||
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حالة التجربة السريرية NCT05408845 لـ سرطان الغدد اللعابية النقيلي، سرطان الغدد اللعابية المتكرر، المرحلة الثالثة من سرطان الغدد اللعابية الكبرى AJCC v8، المرحلة الرابعة من سرطان الغدة اللعابية الكبرى AJCC v8، سرطان الغدد اللعابية غير القابل للاستئصال هي قيد التجنيد. اطلعوا على جميع التفاصيل في عرض البطاقة الخاص برادار التجارب السريرية وأدوات اكتشاف الذكاء الاصطناعي. أو يمكنكم طرح أي سؤال هنا. | ||
Testing the Use of Ado-Trastuzumab Emtansine Compared to the Usual Treatment (Chemotherapy With Docetaxel Plus Trastuzumab) or Trastuzumab Deruxtecan for Recurrent, Metastatic, or Unresectable HER2-Expressing Salivary Gland Cancers
I. To determine if trastuzumab emtansine (ado-trastuzumab emtansine [T-DM1]) shows better progression-free survival (PFS) when compared to docetaxel plus trastuzumab (TH) in recurrent and/or metastatic (R/M) HER2-positive salivary gland cancer (SGC) patients who have not previously received HER2 therapy for unresectable or recurrent and/or metastatic disease, as determined by local assessment. (HER2-Positive Cohort) II. To determine the overall response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 criteria with DS-8201a (trastuzumab deruxtecan) in R/M HER2-low expressing SGC patients. (HER2-Low Expressing Cohort)
SECONDARY OBJECTIVES:
I. To compare the overall response rate (ORR) by RECIST v1.1 criteria between arms. (HER2-Positive Cohort) II. To compare overall survival (OS) between arms. (HER2-Positive Cohort) III. To compare toxicity using Common Terminology Criteria for Adverse Events (CTCAE) v5.0 criteria between arms. (HER2-Positive Cohort) IV. To assess patient-reported toxicity, as measured by the patient reported outcome (PRO)-CTCAE, between arms, and explore patient-reported symptomatic adverse events (AEs) for tolerability of each treatment arm as measured by the PRO-CTCAE. (HER2-Positive Cohort) V. To assess PFS with DS-8201a (trastuzumab deruxtecan) in HER2-low expressing SGC patients. (HER2-Low Expressing Cohort) VI. To assess OS with DS-8201a (trastuzumab deruxtecan) in HER2-low expressing SGC patients. (HER2-Low Expressing Cohort) VII. To evaluate toxicity of DS-8201a (trastuzumab deruxtecan) using CTCAE v5.0. (HER2-Low Expressing Cohort)
EXPLORATORY OBJECTIVES:
I. To assess the ORR in patients who receive crossover treatment to T-DM1/TH following disease progression on the TH arm/T-DM1 arm.
II. To collect blood and tissue specimens for future translational science studies to examine how tumor genetics, HER2 signaling output/expression, HER2 tumoral heterogeneity, and androgen receptor expression/signaling impacts H and T-DM1 efficacy in the HER2-positive cohort and DS-8201a (trastuzumab deruxtecan) efficacy in the HER2-low expressing cohort.
OUTLINE: Patients with HER2-positive disease are randomized to 1 of 2 arms. Patients with HER2-low expression disease are assigned to Arm III.
ARM I: Patients receive docetaxel intravenously (IV) over 60 minutes on day 1 of each cycle. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive trastuzumab IV over 90 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients on Arm I (TH) can cross over to Arm II (T-DM1) after first progression. Patients undergo a computed tomography (CT) scan or magnetic resonance imaging (MRI) and echocardiography (ECHO) or multigated acquisition (MUGA) scan throughout the trial. Patients may also undergo blood sample collection during screening and on study, as well as a biopsy during screening.
ARM II: Patients receive trastuzumab emtansine IV over 90 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients on Arm II (T-DM1) can cross over to Arm I (TH) after first progression. Patients undergo a CT scan or MRI and ECHO or MUGA scan throughout the trial. Patients may also undergo blood sample collection and during screening and on study, as well as a biopsy during screening.
ARM III: Patients receive trastuzumab deruxtecan IV over 30-90 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan or MRI and ECHO or MUGA scan throughout the trial. Patients may also undergo blood sample collection and during screening and on study, as well as a biopsy during screening.
After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for an additional 3-5 years, then annually.
A Phase II Trial of HER2-Targeted Therapies for Recurrent, Metastatic, or Unresectable HER2-Expressing Salivary Gland Cancers
- NRG-HN010
- NCI-2022-04353 (معرف السجل) (CTRP (Clinical Trial Reporting Program))
- NRG-HN010 (معرف آخر) (NRG Oncology)
- NRG-HN010 (معرف آخر) (CTEP)
- U10CA180868 (منحة/عقد NIH الأمريكي)
| مجموعة المشاركين/مجموعة | تَدَخُّل/علاج |
|---|---|
مقارن نشطArm I (docetaxel, trastuzumab) Patients receive docetaxel IV over 60 minutes on day 1 of each cycle. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive trastuzumab IV over 90 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients on Arm I (TH) can cross over to Arm II (T-DM1) after first progression. Patients undergo a CT scan or MRI throughout the trial. Patients may also undergo blood sample collection and during screening and on study, as well as a biopsy during screening. | Biopsy Procedure Undergo a biopsy جمع العينات البيولوجية Undergo blood sample collection التصوير المقطعي المحوسب Undergo a CT scan Docetaxel Given IV التصوير بالرنين المغناطيسي Undergo MRI إدارة الاستبيان Ancillary studies Trastuzumab Given IV |
تجريبيةArm II (trastuzumab emtansine) Patients receive trastuzumab emtansine IV over 90 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients on Arm II (T-DM1) can cross over to Arm I (TH) after first progression. Patients undergo a CT scan or MRI throughout the trial. Patients may also undergo blood sample collection and during screening and on study, as well as a biopsy during screening. | Biopsy Procedure Undergo a biopsy جمع العينات البيولوجية Undergo blood sample collection التصوير المقطعي المحوسب Undergo a CT scan التصوير بالرنين المغناطيسي Undergo MRI إدارة الاستبيان Ancillary studies Trastuzumab Emtansine Given IV |
تجريبيةArm III (trastuzumab deruxtecan) Patients receive trastuzumab deruxtecan IV over 30-90 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan or MRI and ECHO or MUGA scan throughout the trial. Patients may also undergo blood sample collection and during screening and on study, as well as a biopsy during screening. | Biopsy Procedure Undergo a biopsy جمع العينات البيولوجية Undergo blood sample collection التصوير المقطعي المحوسب Undergo a CT scan Echocardiography Test Undergo ECHO التصوير بالرنين المغناطيسي Undergo MRI مسح الاقتناء المتعدد البوابات Undergo MUGA Trastuzumab Deruxtecan Given IV |
| مقياس النتيجة | وصف القياس | الإطار الزمني |
|---|---|---|
Progression free survival (PFS) (HER2-Positive Cohort) | Kaplan-Meier method will be used to estimate PFS rates. A log-rank test will be used to assess whether trastuzumab emtansine (T-DM1) shows a signal of better PFS than the control arm. Cox proportional hazards models, including the stratification factors and with/out other key covariates (e.g., Zubrod performance status), will be used to estimate the treatment effect hazard ratio along with 80% and 95% confidence intervals. | From randomization to disease progression or death due to any cause, whichever occurs first, assessed up to 5 years |
Objective response rate (ORR) (HER2-Low Expressing Cohort) | Overall tumor response in patients will be assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Defined as the proportion of subjects who achieved the best overall response (BOR) of complete response (CR) or partial response (PR). NOTE: For an individual patient, BOR is the best response (in the order of CR, PR, stable disease \[SD\], and progressive disease \[PD\]). Summary statistics of the ORR posterior distribution and 95% credible intervals will also be provided. | From the start of treatment up to a year or until the progression of disease, unacceptable toxicity, physician discretion to discontinue treatment, or patient withdrawal of consent, whichever occurs first.), assessed up to 5 yeats |
| مقياس النتيجة | وصف القياس | الإطار الزمني |
|---|---|---|
ORR (HER2-Positive Cohort) | Overall tumor response in patients will be assessed according to RECIST 1.1. Only randomized patients who have measurable disease present at baseline will be considered evaluable for response. The ORR, defined as the proportion of complete and partial best overall responses (CR+PR) will be calculated with their respective 80% and 95% confidence intervals (CI) based normal approximations. | Up to 5 years |
Duration of response (DOR) (HER2-Positive Cohort) | If the number of responders is sufficient, the Kaplan-Meier method will be used to estimate the DOR rates along with median of DOR and 95% CIs. | From the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 5 years |
Overall survival (OS) (HER2-Positive Cohort) | OS rates will be estimated using the Kaplan-Meier method, and between-arms comparison will be performed using a logrank test (0.10 one-sided significance level). Cox proportional hazards models with the stratification factors and with/out other key covariates (e.g., Zubrod performance status) will be used to estimate the treatment effect hazard ratio along with 80% and 95% confidence intervals. | Up to 5 years |
Incidence of adverse events (HER2-Positive Cohort) | Adverse events (AEs) will be graded using Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0. Counts of all adverse events (AEs) by grade will be provided by treatment arm. Counts and frequencies will be provided for the worst grade AE experienced by the patient by treatment arm. The proportion of patients with at least one grade 3 or higher AE will be compared between the treatment arms. All comparisons will be tested using a chi-Square test, or Fisher's exact test if cell frequencies are \< 5, with a significance level of 0.10. In addition, 80% and 95% confidence intervals will be provided for these proportions. | Up to 30 days from last study treatment dose |
Treatment discontinuations due to AEs (HER2-Positive Cohort) | The proportion of treatment discontinuations due to adverse events between arms will be compared using a chi-Square test (two-sided alpha of 0.10). In addition, 80% and 95% confidence intervals will be provided for these proportions. A two-group chi-square test with a 10% two-sided significance level will have 90% power to detect the difference between Arm 2 proportion of 0.15 and Arm 1 proportion of 0.40 (odds ratio of 3.8) when the number of randomized patients in each group is 58. These figures are reasonable based on data from breast cancer trials (40.9% versus \[vs.\] 7.2% for docetaxel plus trastuzumab \[TH\] and T-DM1 alone). | Up to 5 years |
Patient-reported toxicity (HER2-Positive Cohort) | Patient-reported adverse events will be assessed using selected PRO-CTCAE. | Up to 5 years |
OS (HER2-Low Expressing Cohort) | Will be estimated using the Kaplan-Meier method, and 95% pointwise confidence intervals for 1-year rates will be calculated using the log-log transformation. | Time from treatment initiation to death of any cause, assessed up to 5 years |
PFS (HER2-Low Expressing Cohort) | Will be estimated using the Kaplan-Meier method, and 95% pointwise confidence intervals for 1-year rates will be calculated using the log-log transformation. | Time from treatment initiation to disease progression or death of any cause, assessed up to 5 years |
Incidence of adverse events (HER2-Low Expressing Cohort) | AEs will be graded using CTCAE v5.0. Counts of all AEs by grade will be provided. Counts and frequencies will be provided for the worst grade AE experienced by the patient. The proportion of patients with at least one grade 3 or higher AE will be summarized. | Up to 5 years |
Pathologically (histologically or cytologically) proven diagnosis of HER2-positive OR HER2-low expressing recurrent/metastatic salivary gland cancer (SGC)
HER2-positive cohort:
Note: The majority of HER2-positive SGCs are salivary duct carcinoma (SDCs), but to a lesser extent, other SGC subtypes can be HER2-positive (e.g., adenocarcinomas, mucoepidermoid carcinomas, etc.) and are eligible to be included on the study. Additionally, pathologists may sign out SDCs under other descriptors (e.g., ex-pleomorphic adenoma, adenocarcinoma), and these would be eligible if they are HER2-positive.
Note: HER2 evaluation based on local site immunohistochemistry (IHC), fluorescent in-situ hybridization (FISH), or local/commercial next-generation sequencing (NGS) is required. Any one of the following criteria observed in a primary tumor or metastasis would meet the study definition for "HER2-positive":
- Immunohistochemistry (IHC) (3+) per the College of American Pathologists (CAP) breast cancer guidelines
- Gene amplification by FISH (HER2/CEP17 ratio >= 2.0)
- Gene amplification by NGS (fold change >= 2)
HER2-low expressing cohort:
Note: Local HER2 evaluation by immunohistochemistry (IHC) or fluorescent in-situ hybridization (FISH) is required. Any one of the following criteria observed in a primary tumor or metastasis would meet the study definition for "HER2-low":
- IHC 1+ per the College of American Pathologists (CAP) breast cancer guidelines
- IHC 2+ without evidence of amplification by FISH
Patients with unresectable disease who are not candidates for curative surgery or radiation OR recurrent OR metastatic disease that is evident on radiologic imaging
Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression
- Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of therapy
HER2-positive cohort: Measurable or non-measurable disease by the RECIST v1.1 criteria. HER2-low expressing cohort: Measurable disease by the RECIST v1.1 criteria
History/physical examination within 30 days prior to registration
The following imaging within 60 days prior to registration:
- CT or MRI of the neck (diagnostic quality with contrast, unless contraindicated) AND
- CT scan of the chest (diagnostic quality with contrast, unless contraindicated) AND
- If clinically indicated, CT or MRI of the abdomen and pelvis (diagnostic quality with contrast, unless contraindicated)
Age >= 18
Left ventricular ejection fraction (LVEF) >= 50% assessed by echocardiogram or multigated acquisition (MUGA) scan within 30 days prior to registration
Zubrod (Eastern Cooperative Oncology Group [ECOG]) Performance Status of 0-2 within 14 days prior to registration
Absolute neutrophil count (ANC) >= 1,500 cells/mm^3 (within 14 days prior to registration)
Platelets >= 100,000 cells/mm^3 (within 14 days prior to registration)
Hemoglobin >= 9.0 g/dL (within 14 days prior to registration)
- HER2-positive cohort: Note: The use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 9.0 g/dL is acceptable
- HER2-low expressing cohort: Note: Transfusion (red blood cell or platelet) or granulocyte-colony stimulating factor (granulocyte colony-stimulating factor [G-CSF]) is not allowed
Serum creatinine =< 1.5 x upper limit of normal (ULN) OR calculated creatinine clearance (CrCl) >= 30 mL/min by the Cockcroft-Gault formula (within 14 days prior to registration)
HER2-positive cohort: Total bilirubin =< 1.5 x ULN (within 14 days prior to registration) (Not applicable to patients with known Gilbert's syndrome) (within 14 days prior to registration)
HER2-positive cohort: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 1.5 x ULN (within 14 days prior to registration)
HER2-low expressing cohort: Total bilirubin ≤ 1.5 x ULN if no liver metastases; or < 3 x ULN in the presence of documented Gilbert's Syndrome or liver metastases (within 14 days prior to registration) (within 14 days prior to registration)
HER2-low expressing cohort: AST and ALT ≤ 3 x ULN if no liver metastases; or < 5 x ULN with liver metastases (within 14 days prior to registration)
HER2-low expressing cohort: Serum albumin ≥ 2.5 g/dL (within 14 days prior to registration)
Known human immunodeficiency virus (HIV) infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months prior to registration are eligible for this trial. Testing is not required for entry into protocol
For patients with known evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
- Note: Known positive test for hepatitis B virus surface antigen (HBV sAg) indicating acute or chronic infection would make the patient ineligible unless the viral load becomes undetectable on suppressive therapy. Patients who are immune to hepatitis B (anti-hepatitis B surface antibody positive) are eligible (e.g., patients immunized against hepatitis B)
For patients with a known history of hepatitis C virus (HCV) infection, they must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
- Note: Known positive test for hepatitis C virus ribonucleic acid (HCV RNA) indicating acute or chronic infection would make the patient ineligible unless the viral load becomes undetectable on suppressive therapy
Negative urine or serum pregnancy test (in persons of childbearing potential) within 14 days prior to registration. Childbearing potential is defined as any person who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal
Willing to use highly effective contraceptives for participants of childbearing potential (participants who may become pregnant or who may impregnate a partner) during therapy and for 7 months following last dose of study drug; this inclusion is necessary because the treatment in this study may be significantly teratogenic. Women must refrain from donating eggs during this same period
Men with partners of childbearing potential must be willing to use a highly effective form of non-hormonal contraception or two effective forms of non-hormonal contraception by the patient and/or partner, and to continue the use of contraception for the duration of study treatment and for at least 7 months after the last dose of study treatment. Male patients whose partners are pregnant should use condoms for the duration of the pregnancy. Men must refrain from donating sperm during this same period
Prior to registration, patients who have had chemotherapy or palliative-intent radiotherapy must have all toxicities related to prior treatment recovered to ≤ grade 1
Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal health information
HER2-positive cohort: Prior systemic therapy for the study cancer in the unresectable or recurrent and/or metastatic disease setting
- Note: Prior chemotherapy for a different cancer is allowed; prior androgen receptor targeted therapy in any setting is allowed; prior systemic therapy, including HER2-directed therapies given as neoadjuvant therapy, adjuvant therapy, and/or concurrently with radiation is allowed
HER2-low expressing cohort: HER2 directed therapy for unresectable or recurrent or metastatic disease is not allowed
Severe, active co-morbidity defined as follows:
- Unstable angina requiring hospitalization in the last 6 months
- Myocardial infarction within the last 6 months
- New York Heart Association Functional Classification III/IV (Note: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification.)
- Persistent grade 3-4 (CTCAE version 5.0) electrolyte abnormalities that cannot be reversed despite replacement as indicated by repeat testing
- Patient must not have an active infection requiring IV antibiotics, antivirals, or antifungals
HER2-positive cohort only: >= grade 3 peripheral neuropathy
Interstitial lung disease or pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on chest CT scan
Any hemorrhage or bleeding event grade >= 3 within 28 days prior to registration
History of allergic reactions to compounds of similar chemical or biologic composition to: HER2-positive cohort: ado-trastuzumab emtansine, trastuzumab, and/or docetaxel (or any of their excipients). HER2-low expressing cohort: DS-8201a (trastuzumab deruxtecan), trastuzumab
History of exposure to the following cumulative doses of anthracyclines:
- Doxorubicin or liposomal doxorubicin > 500 mg/m^2
- Epirubicin > 900 mg/m^2
- Mitoxantrone > 120 mg/m^2
- Note: If another anthracycline, or more than one anthracycline has been used, the cumulative dose must not exceed the equivalent of doxorubicin 500 mg/m^2
HER2-low expressing cohort only: Receipt of live, attenuated vaccine (messenger ribonucleic acid [mRNA and replication deficient adenoviral vaccines are not considered attenuated live vaccines) within 30 days prior to the first dose of DS-8201a (trastuzumab deruxtecan)
Pregnancy and individuals unwilling to discontinue nursing
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