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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

ConditionsMetastatic Salivary Gland CarcinomaRecurrent Salivary Gland CarcinomaStage III Major Salivary Gland Cancer AJCC v8Stage IV Major Salivary Gland Cancer AJCC v8Unresectable Salivary Gland Carcinoma
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorNRG Oncology

About this trial

This phase II trial compares the effect of usual treatment of docetaxel chemotherapy plus trastuzumab, to ado-emtansine (T-DM1) in patients with HER2-postive salivary gland cancer that has come back (recurrent), that has spread from where it first started (primary site) to other places in the body, or cannot be removed by surgery (unresectable). This trial is also testing how well trastuzumab deruxtecan works in treating patients with HER2-low recurrent or metastatic salivary gland cancer. Trastuzumab is a form of targeted therapy because it works by attaching itself to specific molecules (receptors) on the surface of cancer cells, known as HER2 receptors. When trastuzumab attaches to HER2 receptors, the signals that tell the cells to grow are blocked and the cancer cell may be marked for destruction by body's immune system. Trastuzumab emtansine contains trastuzumab, linked to a chemotherapy drug called emtansine. Trastuzumab attaches to HER2 positive cancer cells in a targeted way and delivers emtansine to kill them. Trastuzumab deruxtecan is a monoclonal antibody called traztuzumab, linked to a chemotherapy drug called deruxtecan. Trastuzumab is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of cancer cells, known as HER2 receptors and delivers deruxtecan to kill them. Docetaxel is in a class of medications called taxanes. It stops cancer cells from growing and dividing and may kill them. Trastuzumab emtansine may work better compared to usual treatment of chemotherapy with docetaxel and trastuzumab or trastuzumab deruxtecan in treating patients with recurrent, metastatic or unresectable salivary gland cancer.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Pathologically (histologically or cytologically) proven diagnosis of HER2-positive OR HER2-low expressing recurrent/metastatic salivary gland cancer (SGC)

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.

Immunohistochemistry (IHC) (3+) per the College of American Pathologists (CAP) breast cancer guidelines

Gene amplification by FISH (HER2/CEP17 ratio >= 2.0)

Disqualifiers

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

Unstable angina requiring hospitalization in the last 6 months

Trial design

Design model

Parallel

Treatments tested in this trial

  • Biopsy Procedure

    Procedure/Surgery

    Undergo a biopsy

  • Biospecimen Collection

    Procedure/Surgery

    Undergo blood sample collection

  • Computed Tomography

    Procedure/Surgery

    Undergo a CT scan

  • Docetaxel

    Drug

    Given IV

  • Echocardiography Test

    Procedure/Surgery

    Undergo ECHO

  • Magnetic Resonance Imaging

    Procedure/Surgery

    Undergo MRI

  • Multigated Acquisition Scan

    Procedure/Surgery

    Undergo MUGA

  • Questionnaire Administration

    Other intervention

    Ancillary studies

  • Trastuzumab

    Biological/Vaccine

    Given IV

  • Trastuzumab Deruxtecan

    Biological/Vaccine

    Given IV

  • Trastuzumab Emtansine

    Biological/Vaccine

    Given IV

Treatment groups

146 Participants
are divided into 3 treatment groups
Group A: Arm I (docetaxel, trastuzumab)Active comparator 7 interventions
Group B: Arm II (trastuzumab emtansine)Experimental treatment 6 interventions
Group C: Arm III (trastuzumab deruxtecan)Experimental treatment 7 interventions

Trial outcomes

Primary outcomes

1

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.

Time frame
From randomization to disease progression or death due to any cause, whichever occurs first, assessed up to 5 years
2

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.

Time frame
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

Secondary outcomes

1

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.

Time frame
Up to 5 years
2

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.

Time frame
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
3

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.

Time frame
Up to 5 years
4

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.

Time frame
Up to 30 days from last study treatment dose

Other outcomes

1

Objective Response Rate (ORR) for patients who receive crossover treatment to T-DM1/TH following disease progression on the TH/T-DM1 arm

Overall tumor response will be assessed by RECIST v1.1 (see Section 13). The ORR, defined as the proportion of complete and partial responses (CR+PR) for patients who crossover after disease progression from T-DM1 (TH) to TH (T-DM1) will be calculated with their respective 80% and 95% CIs.

Time frame
Up to 5 years

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

NRG Oncology

Lead sponsor

National Cancer Institute (NCI)

Collaborator

Source ClinicalTrials.gov
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