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Closed (no longer recruiting)Last updated: 2 February 2024

ALKternate: This phase I/II trial is trying to understand whether alternating between two targeted therapies will improve treatment outcomes for patients with ALK-rearranged non-small cell lung cancerA single arm multi-centre translational proof of concept study investigating the safety and efficacy of alternating lorlatinib with crizotinib in a pre-treated advanced ALK-rearranged non-small cell lung cancer population with disease progression on a 2nd generation ALK tyrosine kinase inhibitor

Clinical summary

Summary

Eligible patients will receive induction therapy with oral lorlatinib, every day for 12 weeks. Participants will then move onto the alternating phase of the trial, in which patients will receive crizotinib for 4 weeks, then lorlatinib for 8 weeks, then crizotinib for another 4 weeks, and lorlatinib for 8 weeks until disease progression or unacceptable side effects are experienced/observed. Following progression, some participants may be eligible to continue with alternating treatment or switch to continuous treatment until further progression, depending on the potential clinical benefit.

Conditions

This trial is treating patients with ALK-rearranged non-small cell lung cancer.

Cancer

Lung Cancers Lung cancer

Age

People18+

Phase

I/II

Trial Acronym

ALKternate

More information

Trial Identifiers

Use the hyperlinks, where available to access additional clinical trial information.

Trial sponsor

Pfizer

Scientific Title

A single arm multi-centre translational proof of concept study investigating the safety and efficacy of alternating lorlatinib with crizotinib in a pre-treated advanced ALK-rearranged non-small cell lung cancer population with disease progression on a 2nd generation ALK tyrosine kinase inhibitor

Eligibility

Inclusion

 

Adults aged >=18 years with pathologically confirmed stage IV ALK gene rearranged NSCLC (predominately adenocarcinoma phenotype) by IHC and or FISH, fresh or archival, not required to be reconfirmed centrally
Confirmed radiological disease progression on prior second generation ALKi as per RECIST Version 1.1
Any prior number of lines of systemic therapy, provided the most recent ALKi was a second generation agent
Extracranial RECIST measurable disease confirmed =28 days prior to start of study
Eastern Co-operative Oncology Group (ECOG) performance status =1
Patients with asymptomatic CNS disease including leptomeningeal disease are eligible
Patients with symptomatic CNS disease including leptomeningeal disease are eligible if treated with local therapy(ies) including surgery and or radiotherapy and stable clinically with stable steroid requirements for >=14 days
Patients with oligo-progression in the CNS are eligible, provided they meet criteria above Adequate bone marrow function (e.g. platelets > 100 x 109/L, ANC = 1.5 x 109/L, Hb =90)
Adequate liver function (e.g. ALT/AST < = 3 x ULN; if liver metastases <= 5 x ULN, bilirubin <= 2 x ULN)
Adequate renal function (e.g. creatinine clearance >= 50 ml/min, serum creatinine <= 1.5 x ULN)
Study treatment both planned and able to start within 14 days of registration
Willing and able to comply with all study requirements, including treatment (e.g. able to swallow tablets), timing and/or nature of required assessments (e.g. able to have IV contrast if this is required for tumour assessments)
Signed, written informed consent (for trial inclusion and tissue collection)
Prior screen failure patients are eligible for rescreening

Exclusion

Most recent systemic treatment is crizotinib
Prior hypersensitivity to crizotinib
Primary resistance to first line ALKi therapy (first or second generation ALKi)
Prior lorlatinib therapy or other third generation ALKi therapy
Prior toxicity to crizotinib contraindicating further use
Previous ALKi therapy within 4 days, or chemotherapy or radiotherapy within 7 days
Specific comorbidities or conditions affecting compliance to clinical trial
Life expectancy of less than 3 months
Inability to tolerate or contraindication to MRI-B imaging
No measurable disease via RECIST criteria extra-cranially
Significant cardiac dysfunction
Untreated and or non-clinically stable symptomatic CNS including leptomeningeal disease
Past history of malignancy except the following whom are eligible: adequately treated carcinoma-in-situ, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial transitional cell carcinoma of the bladder, or curatively treated cervical carcinoma in situ. Patients with a history of other malignancies are eligible if they have been continuously disease free for at least 5 years after definitive primary treatment, with the exception of men with prostate cancer, eligible if PSA and radiological control for at least 2 years
Significant uncontrolled infection, including chronic active hepatitis B, hepatitis C, or HIV.
Concurrent illness, including severe infection that may jeopardize the ability of the patient to undergo the procedures outlined in this protocol with reasonable safety
The requirement to continue one of the excluded concomitant medications (Section 8.6)
Serious medical or psychiatric conditions that might limit the ability of the patient to comply with the protocol
Comorbid malabsorption syndrome or other gastrointestinal (GI) illness or condition that could affect oral absorption of the study drug
Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule, including alcohol dependence or drug abuse.
Pregnancy, lactation, or inadequate contraception. Women must be post-menopausal, infertile, or use a reliable means of contraception. Women of childbearing potential must have a negative pregnancy test done within 7 days prior to registration. Men must have been surgically sterilised or use a (double if required) barrier method of contraception.
An inability to travel to the enrolled site to participate in the trial and all required visits

Inclusion

  • You have had treatment but your cancer has gotten worse or has not responded to the treatment you have been given.

Exclusion

  • You have been diagnosed with a prior or secondary type of cancer.
  • You have certain types of non-cancer medical conditions.
  • You have had certain treatments, surgical procedures or drugs.
Message

Clinical trials have complex eligibility criteria.

Ask your doctor if this trial could be right for you.

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