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RecruitingLast updated: 20 February 2024

MoST addendum 13 (substudy 31): This Phase II trial is evaluating how safe and tolerable a targeted therapy (entrectinib) is in people with newly diagnosed non-squamous non-small cell lung cancer an advanced solid cancers with NTRK fusions or ROS1 gene rearrangementsA single-arm, open-label, phase II trial of the tumour response to entrectinib in patients with advanced tumours harbouring NTRK fusions or ROS1 gene rearrangements detected by comprehensive genomic profiling

Clinical summary

Summary

This is a substudy of the Cancer Molecular Screening and Therapeutics (MoST) Program (ACTRN12616000908437). All participants in this trial will be treated with Entrectinib. Entrectinib will be administered orally at a dose of 600mg once daily from days 1-28 on a 28-day cycle until disease progression, intolerable toxicity or withdrawal.

Conditions

This trial is treating patients with non-squamous non-small cell lung cancer and advanced solid cancers

Cancer

Multi-Cancer Multi-Cancer

Age

People18+

Phase

II

Trial Acronym

MoST addendum 13 (substudy 31)

More information

Trial Identifiers

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Trial sponsor

University of Sydney,Australian Genomic Cancer Medicine Centre

Scientific Title

A single-arm, open-label, phase II trial of the tumour response to entrectinib in patients with advanced tumours harbouring NTRK fusions or ROS1 gene rearrangements detected by comprehensive genomic profiling

Eligibility

Inclusion

1. Adults, aged 18 years and older with either pathologically confirmed:
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 an NTRK fusion or ROS1 activating gene alteration identified using CGP
3. NSCLC patients identified through the ASPiRATION molecular screening program must be FISH-negative, i.e. ineligible for PBS-reimbursed ROS1-targeted treatment
4. Confirmation of molecular eligibility by the molecular tumour board (MTB)
5. Measurable disease as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and/or RANO.
6. ECOG 0-2
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
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 90g/L;
b. liver function; ALT/AST less than or equal to 2.5 x ULN (in the absence of liver metastases, ALT/AST less than or equal to 5 x ULN for patients with liver metastases) and total bilirubin =1.5xULN;
c. renal function; serum creatinine less than or equal to 1.5xULN;
9. Prior anticancer therapy (excluding TRK or ROS1 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 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
10. Life expectancy greater than or equal to 12 weeks
11. Willing and able to comply with all study requirements, including treatment (including ability to swallow whole capsules intact, without chewing, crushing, or opening the capsules/tablets), timing and/or nature of required assessments
12. Signed, written informed consent to participation in this specific treatment substudy

Exclusion

1. Prior NTRK and/or ROS1 pathway inhibitor treatment (either approved or investigational)
2. Known history of hypersensitivity or contraindication to entrectinib
3. History of prolonged QTc interval (e.g. repeated demonstration of a QTc interval greater than 450 milliseconds from ECGs performed at least 24 hours apart) or use of medications that are known to prolong the QT interval.
4. History of additional risk factors for torsade de pointes (e.g. family history of long QT syndrome)
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. Peripheral sensory neuropathy grade greater than or equal to 2
7. Known interstitial lung disease, interstitial fibrosis, or history of tyrosine kinase inhibitor-induced pneumonitis
8. Radiation therapy, major surgery, or tumour embolization within 14 days prior to the first dose of entrectinib. Palliative radiotherapy (for analgesia) is acceptable only if the irradiated field does not include target lesions;
9. Any systemic therapy within 28 days prior to the first dose of entrectinib
10. Administration of any investigational treatment within 28 days prior to receiving the first dose of entrectinib
11. Specific comorbidities or conditions (e.g. psychiatric) or concomitant medications which may interact with entrectinib, including
a. Known active infections that would interfere with the assessment of safety or efficacy of entrectinib (bacterial, fungal, or viral, including HIV positive)
b. Active gastrointestinal disease (e.g. Crohn’s disease, ulcerative colitis, or short gut syndrome) or other malabsorption syndromes that would reasonably affect drug absorption
12. 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;
13. Any unresolved toxicity (CTCAE v5.0 greater than grade 2) from previous anti-cancer therapy.
14. 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
15. 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 7 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

Inclusion

  • You are able to swallow medication by mouth.
  • You have been diagnosed with cancer, but have not received any treatment.
  • 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.
Message

Clinical trials have complex eligibility criteria.

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

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