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RecruitingLast updated: 2 February 2024

MoST Addendum 6 (substudy 14-15): This phase II study is evaluating the effectiveness of an anticancer drug (larotrectinib) in people with advanced solid cancers with NTRK1-3 rearrangementsSingle arm, open label, signal seeking, phase IIa trial of the activity of Larotrectinib in patients with advanced NTRK1-3 positive tumours

Clinical summary

Summary

This is a substudy within the Cancer Molecular Screening and Therapeutics (MoST) Program (ACTRN12616000908437). Eligible participants will receive larotrectinib, to be taken orally by the participant at home, at a dose of 100mg twice daily. The dose may be reduced to 75mg or 50mg twice daily if the participant experiences intolerance toxicity. **Update 09/01/23: PCCTU is currently only open to recruitment to people with cancers of the Central Nervous System**

Cancer

Multi-Cancer Multi-Cancer

Age

People18+

Phase

II

Trial Acronym

MoST Addendum 6 (substudy 14-15)

More information

Trial Identifiers

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Trial sponsor

University of Sydney,Australian Genomic Cancer Medicine Centre

Scientific Title

Single arm, open label, signal seeking, phase IIa trial of the activity of Larotrectinib in patients with advanced NTRK1-3 positive tumours

Eligibility

Inclusion

 

1. Adults, aged 18 years and older, with pathologically confirmed advanced and/or metastatic solid cancer of any histologic type or an earlier diagnosis of a poor prognosis cancer.
2. Confirmation of molecular eligibility by the molecular tumour board, patients with tumours harbouring somatic NTRK1-3 rearrangements/ fusions OR extreme overexpression of NTRK1,2 or 3
3. For non primary CNS cancers, at least one site of measurable disease according to RECIST version 1.1.
4. For primary CNS tumours, the following additional inclusion criteria must be met:
a. Radiation as first line therapy, if given, completed more than 12 weeks prior to C1D1 of study treatment
b. At least one site of bi-dimensionally measurable disease (confirmed by magnetic resonance imaging [MRI] and evaluable by RANO criteria), with the size of at least one of the measurable lesions greater or equal to 1 cm in each dimension and noted on more than one imaging slice
c. Baseline imaging done while on a stable dose of steroid medication for at least 5 days immediately before the MRI
5. ECOG performance status 0, 1 or 2
6. Received and failed all standard anticancer therapy or have documented unsuitability for any further standard therapy, if standard therapy exists
7. Clinical or radiological progression on or following last anticancer therapy unless such anticancer therapy stopped due to toxicity / treatment intolerance
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 greater than or equal to 100 x 10^9/L, ANC greater than or equal to 1.5 x 10^9/L, and haemoglobin greater than or equal to 9g/dL (5.6mmol/L);
b. liver function; ALT/AST less than or equal to 3 x ULN (in the absence of liver metastases, less than or equal to 5 x ULN for patients with liver involvement) and total bilirubin less than or equal to 1.5xULN;
c. renal function; serum creatinine less than or equal to 1.5xULN
9. Willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessments
10. Signed, written informed consent to participation in the specific treatment substudy

Exclusion

1. Amongst patients eligible on the basis of extreme overexpression of NTRK1-3, patients whose tumours also harbor gain-of-function mutations in KRAS, NRAS, BRAF, MAP2K1, EGFR, ALK, RET, ROS1, KIT, PDGFRA will not be eligible.
2. Contraindications to investigational product;
3. Known history of hypersensitivity to active or inactive components of investigational product;
4. Previous treatment with a NTRK inhibitor
5. Patients unable or unwilling to swallow capsules or oral solution
6. Treatment with strong inhibitors or inducers of CYP3A4 within 7 days of registration
7. Patients who require treatment with an enzyme-inducing anti-epileptic drug
8. Specific comorbidities or conditions (e.g. psychiatric) or concomitant medications which may interact with the investigational product(s);
9. 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;
10. Treatment with any of the following anti-cancer therapies prior to the first dose of study treatment:
a. Radiation therapy, 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. Immunotherapy within 28 days prior to the first dose of study treatment;
c. Chemotherapy, biologic therapy, or hormonal therapy within 14 days or 5 half-lives of a drug prior to the first dose of study treatment or until recovery from previous therapy (whichever is longer);
11. Any unresolved toxicity (greater than 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);
12. Administration of any investigational treatment within 30 days or 5 half-lives (whichever is longer) prior to receiving the first dose of study treatment;
13. For non central nervous system (CNS) cancers, patients with symptomatic CNS involvement of his/her cancer are excluded. Subjects with stable neurological function, on stable doses of steroids/anti-epileptics over 4 weeks, and with no evidence of CNS progression within 12 weeks prior to screening are eligible;
14. History of another malignancy within 2 years prior to molecular screening registration are excluded unless adequately treated and determined free of progressive and metastatic disease for at least 6 months. Patients with a past history of adequately treated carcinoma-in-situ, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or superficial transitional cell carcinoma of the bladder can be included;
15. 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.

Inclusion

  • You are able to swallow medication by mouth.
  • You have had treatment but your cancer has gotten worse or has not responded to the treatment you have been given.
  • Your cancer has not spread to other parts of the body.
  • Your cancer has spread to other parts of the body.

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.
  • You have previously been treated (or are currently being treated) on a clinical trial.
Message

Clinical trials have complex eligibility criteria.

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

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