Cancer Molecular Screening and Therapeutics (MoST) Program and ASPiRATION subprogram, Addendum 14 – substudy 32: Alectinib
- Conditions
- CancerALK gene alterationsNon-small cell lung cancerCancer - Any cancerCancer - Lung - Non small cell
- Registration Number
- ACTRN12621000312842
- Lead Sponsor
- niversity of Sydney
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 16
1. Adults, aged 18 years and older, with either:
a. newly diagnosed metastatic non-squamous NSCLC identified through the ASPiRATION molecular screening program OR
b. advanced and/or metastatic solid cancer of any histologic type, refractory or unsuitable for standard therapies for that cancer type, identified through the MoST molecular screening program;
2. Harbouring a targetable ALK gene alteration identified using CGP and determined by the molecular tumour board. NSCLC patients who have an ALK gene alteration determined by IHC must be confirmed by NGS; Pan cancer patients who have ALK overexpression determined by IHC or rearrangement diagnosed by FISH must be confirmed by NGS;
3. NSCLC patients identified through the ASPiRATION molecular screening program must be FISH-negative, i.e. not eligible for PBS-reimbursed ALK-targeted treatment;
4. Confirmation of molecular eligibility by the molecular tumour board;
5. Measurable disease as assessed by RECIST 1.1 and/or RANO;. (Exception: newly diagnosed metastatic, non-squamous NSCLC participants with evaluable but non-measurable disease may be approved on a case-by-case basis by contacting the study chair or delegate through the NHMRC CTC).
6. ECOG 0 to 2;
7. 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; radiation treatment must be completed at least 14 days before enrolment and patients must be clinically stable;
8. 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 100 x 109/L, ANC equal 1.5 x 109/L, and haemoglobin equal 90g/L (5.6mmol/L);
b. liver function; ALT/AST equal 3 x ULN (in the absence of liver metastases, equal 5 x ULN for patients with liver involvement) and total bilirubin equal 1.5xULN;
c. renal function; serum creatinine equal 1.5xULN;
9. Prior anticancer therapy:
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 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,
iii. Patients previously treated with an ALK inhibitor (other than alectinib) are eligible, unless there is a known on-target resistant mutation (e.g. G1202R) or a compelling off-target resistance mechanism that is deemed unlikely to respond to alectinib, as determined by the MTB. The tumour sample must be obtained from a progression biopsy for genomic screening instead of the archival sample;
10. Life expectancy of at least 12 weeks
11. Willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessments;
12. Signed, written informed consent to participation in the specific treatment substudy.
1. Prior ALK pathway inhibitor treatment;
2. Known history of hypersensitivity or contraindication to alectinib, or to any of the additives in the alectinib drug formulation;
3. Specific comorbidities or conditions (e.g. psychiatric) or concomitant medications which may interact with alectinib, including:
a. GI disorder that may significantly affect absorption of oral medications, such as malabsorption syndromes or status post-major bowel resection
b. Symptomatic bradycardia
4. 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;
5. Treatment with any of the following anti-cancer therapies prior to the first dose of alectinib:
a. Radiation therapy, major surgery, or tumour embolization within 14 days prior to the first dose of study treatment. Palliative radiotherapy (for analgesia) is acceptable only if the irradiated field does not include target lesions;
b. Any systemic therapy within 28 days prior to the first dose of alectinib;
6. Administration of any investigational treatment within 28 days prior to receiving the first dose of alectinib;
7. Any unresolved toxicity (>CTCAE grade 2) from previous anti-cancer therapy. Subjects with irreversible toxicity that is not reasonably expected to be exacerbated by the investigational product may be included (e.g. hearing loss, peripheral neuropathy);
8. Prior or concurrent malignancy. History of another primary 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;
d. For participants with treatment-refractory solid tumours, a concurrent or past history of competing malignancy within 2 years, prior to molecular screening registration, is eligible, unless the competing malignancy is expected to lead to a shorter survival than the index malignancy;
9. Pregnancy, lactation, or inadequate contraception. Women must be post-menopausal, infertile, or agree to use a highly effective form of contraception. Women of childbearing potential must have a negative pregnancy test done within 3 days prior to registration. Men with partners of childbearing potential must have been surgically sterilised or agree to use a highly effective form of contraception.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method