None listed
Conditions
Brief summary
This is a substudy of the Cancer Molecular Screening and Therapeutics (MoST) Program, which is registered on ANZCTR with ID ACTRN12616000908437. This substudy will evaluate the activity of trastuzumab emtansine (T-DM1) in patients with advanced tumours with HER2 amplification or mutations. Who is it for? You may be eligible to join the study if you are aged 18 years and older with either; a. advanced and/or metastatic solid tumour of any cell type that is no longer responding to treatment or unsuitable for standard therapies for that cancer type, or b. metastatic, non-squamous, non-small cell lung cancer (NSCLC) Participants will have tumours with HER2 alterations Study details Participants will continue to receive T-DM1 intravenously at a dose of 3.6 mg/kg every 21 days continuously as long as they and their doctor agree there is a benefit from treatment. Participants will undergo imaging assessments at 9 weekly intervals or as clinically indicated in order to evaluate tumour response. Safety and tolerability of treatment and health related quality of life during treatment will be assessed at 3 weekly intervals. We cannot guarantee that patients will receive any benefits from this study. This study is being carried out to improve the way we treat cancer patients who may have limited treatment options available to them. It is hoped that T-DM1 will be well tolerated and will improve outcomes for future patients, however, there may be no clear benefit from participation in this study.
Interventions
Trastuzumab emtansine will be administered intravenously at a dose of 3.6 mg/kg every 21 days continuously until disease progression is documented, the patient experiences an intolerable toxicity, or withdraws for another reason.
Sponsors
The University of Sydney
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Adults, aged 18 years and older, with either pathologically confirmed: a. advanced and/or metastatic solid cancer of any histologic type, refractory or unsuitable for standard therapies for that cancer type; or b. metastatic, non-squamous NSCLC 2. Patients with tumours harbouring HER2 mutations or amplification (in the absence of a mutation) (Groups 1 and 2) or HER2 mutation with/without amplification (Groups 3 and 4) identified using comprehensive genomic profiling (CGP) and determined by the molecular tumour board. 3. Confirmation of molecular eligibility by the molecular tumour board 4. Measurable disease as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and/or RANO. (Exception: ASPiRATION participants with evaluable but non-measurable disease may be approved on a case-by-case basis by contacting the ASPiRATION study chair or delegate through the NHMRC CTC). 5. ECOG 0-2 6. If the CNS is involved (either primary or metastatic disease), this must be asymptomatic or previously treated and controlled either with local treatment or by steroids 7. Adequate organ system function as assessed by the following minimal laboratory requirements (within 7 days prior to first administration of study drug): a. bone marrow function; platelets equal or more than 100 x 10^9/L, ANC equal or more than 1.5 x 10^9/L, and haemoglobin equal or more than 9g/dL (5.6mmol/L); b. liver function; ALT/AST equal or less than 2.5 x ULN and total bilirubin equal or less than 1.5xULN; c. renal function: creatinine clearance greater than 50 mL/min based on Cockcroft-Gault glomerular filtration rate (GFR) estimation: (140 - Age) × (weight in kg) × (0.85 if female)/(72 × serum creatinine); 8. Prior anticancer therapy (excluding HER2 inhibitors) a. For newly diagnosed metastatic, non-squamous NSCLC: i. Up to 2 cycles of systemic therapy while awaiting the results of CGP testing are permitted (but not required); b. For second or subsequent line metastatic, non-squamous NSCLC: i. Clinical or radiological progression on, or following last anticancer therapy unless such anticancer therapy stopped due to toxicity / treatment intolerance c. For advanced and/or metastatic treatment-refractory solid cancer of any histologic type: i. Participants must have received and failed all standard anticancer therapy or have documented unsuitability for any further standard therapy, if standard therapy exists. ii. Clinical or radiological progression on, or following last anticancer therapy unless such anticancer therapy stopped due to toxicity / treatment intolerance 9. ALP equal or less than 2.5 ×ULN with the following exception: patients with bone metastases: ALP equal of less than 5 ×ULN 10. INR and aPTT less then 1.5 x ULN (unless on therapeutic coagulation) 11. Albumin equal or more than 25mg/dL 12. Life expectancy greater than or equal to 12 weeks
Exclusion criteria
1. Known history of hypersensitivity or contraindication to T-DM1; 2. Prior treatment with T-DM1, or other HER2-directed therapy; 3. HER2-amplified breast and gastric cancer (breast and gastric cancer with HER2 mutations are permitted); 4. Peripheral neuropathy of grade 2 or higher (according to National Cancer Institute Common Terminology Criteria for Adverse Events [CTCAE], version 5); 5. History of recent (within 3 months prior to screening) symptomatic congestive heart failure or clinically significant cardiac dysfunction as determined by left ventricular ejection fraction (LVEF) less than 50%; 6. Currently diagnosed with interstitial lung disease, interstitial fibrosis or history of tyrosine kinase inhibitor-induced pneumonitis 7. Specific comorbidities or conditions (e.g. psychiatric) or concomitant medications which may interact with the investigational product(s); 8. Co-morbidities or conditions that may compromise assessment of key outcomes or in the opinion of the clinician, limit the ability of the patient to comply with the protocol; 9. Radiation therapy, major surgery or tumour embolization within 14 days prior to the first dose of T-DM1; 10. Any systemic therapy within 28 days prior to the first dose of T-DM1. Any systemic therapy within 21 days prior to the first dose of T-DM1 for ASPiRATION cohort participants who received systemic therapy while awaiting the results of CGP testing.; 11. Any unresolved toxicity ( greater than CTCAE v5.0 grade 2) from previous anti-cancer therapy; 12. Prior or concurrent malignancy except for: a. Malignancy treated with curative intent and with no known active disease within 2 years before consent to molecular screening and of low potential risk for recurrence; b. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease; c. Adequately treated carcinoma-in-situ without evidence of disease 13. Pregnancy, lactation, or inadequate contraception.
Outcome results
None listed