Cancer Molecular Screening and Therapeutics (MoST) Program Substudy Addendum 8 substudy 19: T-DM1
- Conditions
- CancerCancer - Any cancer
- Registration Number
- ACTRN12619001265167
- Lead Sponsor
- The University of Sydney
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 64
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
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.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method The primary end point is disease control defined as:<br>1. Objective tumour response, based on complete and partial responses using cancer specific response criteria or<br>2. Time to progressive disease exceeds the documented time to progressive disease on the last treatment prior to substudy entry by at least 1.3 times (TTP2/TTP1 > 1.3). Or exceeds 6 months if TTP1 is not evaluable. <br><br>Where disease evaluation is not based on CT scans alternative validated guidelines, such as Gynecologic Cancer Intergroup (GCIG) and Prostate Cancer Working Group 2 (PCWG2) criteria will be employed.<br><br>Where radiological progression cannot be assessed, evidence for clinical progression will be documented. These data will be collected from patient questionnaires, such as quality of life per the QLQ-C30 version 3 or The Brief Pain Inventory, or clinical reports to supplement the primary outcome.<br>[ CT or MRI scans for disease evaluation will take place every 9 weeks until disease progression]
- Secondary Outcome Measures
Name Time Method Overall survival (OS) (death from any cause).[ For the duration of the study.];Safety and tolerability of treatment (rates of adverse events). All adverse events (AEs), including event grading as per NCI CTCAE criteria, will be captured from the first dose of study treatment until 30 days after cessation of study treatment. AEs reported by participants will be documented by study site staff and subsequently transcribed onto study electronic data capturing (EDC) system. In order to evaluate the safety and tolerability of the study treatment, the entered AE types, frequency and severity in the EDC will be analysed. [ Adverse events will be recorded from the first dose of study treatment until 30 days after cessation of study treatment.];Health related quality of life during treatment will be assessed using a composite of the EORTC QLQ-C30 and The Brief Pain Inventory Forms[ Every 3 weeks during treatment and every 9 weeks during follow-up until disease progression]