ACTRN12621000284864WithdrawnPhase 2
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
Conditions
Trial Snapshot
- Phase
- Phase 2
- Status
- Withdrawn
- Sponsor
- The University of Sydney
- Enrollment
- 16
Study Overview
Brief Summary
No summary available.
Study Design
- Study Type
- Interventional
- Allocation
- Non-randomised trial
- Primary Purpose
- Treatment
- Masking
- Open (masking not used)
Eligibility Criteria
- Ages
- 18 Years to o limit (—)
- Sex
- All
Inclusion Criteria
- •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 Criteria
- •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
Investigators
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