ActivePhase 2ACTRN12621000312842

Cancer Molecular Screening and Therapeutics (MoST) Program and ASPiRATION subprogram, Addendum 14 – substudy 32: Alectinib

A Single arm, open label, phase II trial of tumour response to alectinib in patients with advanced tumours harbouring ALK gene alterations detected by comprehensive genomic profiling

Sponsor

University of Sydney

Enrollment

16 participants

Start Date

Sep 3, 2021

Study Type

Interventional

Conditions

Cancer ALK gene alterations

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 alectinib in a population of participants with newly diagnosed metastatic non-squamous small cell lung cancer (NSCLC) or patients with advanced cancers harbouring ALK gene alterations identified using comprehensive genomic profiling (CGP). Who is it for? You may be eligible to join the study if you are aged 18 years and older, with pathologically confirmed advanced and/or metastatic NSCLC or solid tumour of any histologic type or an earlier diagnosis of a poor prognosis cancer. Your tumour will need to harbour ALK gene alterations identified using CGP. Study details: Participants will receive alectinib treatment. The alectinib is to be taken orally, at 600mg twice daily (days 1 to 28 in a 28-day treatment cycle). Alectinib will be given to participants continuously as long as they and their doctor agree there is a benefit from treatment. Participants will undergo imaging assessments at 8 weekly intervals from first treatment until progression. Safety and tolerability of treatment will be assessed at 4 weekly intervals. Health related quality of life during treatment will be assessed at 4 weekly intervals and then every 8 weeks after end of treatment until progression. We cannot guarantee that participants 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 Alectinib will be well tolerated and will improve outcomes for future patients, however, there may be no clear benefit from participation in this study.

Eligibility

Sex: Both males and femalesMin Age: 18 Yearss

Inclusion Criteria23

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;
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;
NSCLC patients identified through the ASPiRATION molecular screening program must be FISH-negative, i.e. not eligible for PBS-reimbursed ALK-targeted treatment;
Confirmation of molecular eligibility by the molecular tumour board;
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).
ECOG 0 to 2;
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;
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;
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;
Life expectancy of at least 12 weeks
Willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessments;
Signed, written informed consent to participation in the specific treatment substudy.

Exclusion Criteria17

Prior ALK pathway inhibitor treatment;
Known history of hypersensitivity or contraindication to alectinib, or to any of the additives in the alectinib drug formulation;
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
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;
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;
Administration of any investigational treatment within 28 days prior to receiving the first dose of alectinib;
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);
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;
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.

Interested in this trial?

Get notified about updates and connect with the research team.

Interventions

Participants will recieve continuous alectinib 600mg capsules, twice a day until disease progression, participant withdrawal or unnaceptable toxicity. If participants experience any severe (grade

Participants will recieve continuous alectinib 600mg capsules, twice a day until disease progression, participant withdrawal or unnaceptable toxicity. If participants experience any severe (grade 3-4) adverse events, treatment will be withheld until the adverse event is resolved (grade 0-1). Once the adverse event is resolved, the patient should continue on their prescribed dose of alectinib. If participants experience intolerance toxicity, alectinib dose may be reduced to 540mg twice daily, and then to 300mg twice daily if participants experience further intolerance toxicity. If a third dose reduction is required, the patient should discontinue study treatment. There is no maximum number of treatment cycles that alectinib will be taken for. Participants will continuously receive alectinib until disease progression is documented or when the participants experience intolerable toxicity or withdraws for another reason. Participants will be asked to return unused drug and empty drug containers at each return visit. The Pharmacy Department at participating institutions will maintain a record of drugs dispensed for each participant.