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New treatment option for Thyroid Cancer
Official title A Study of Avutometinib and Defactinib in People With Thyroid Cancer
ClinicalTrials.gov ID: NCT06007924
What this study is testing
What is Avutometinib?
Avutometinib is an investigational medicine, given as an once-weekly, being studied as a potential treatment for thyroid cancer.
Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- The researchers are doing this study to find out if the combination of avutometinib and defactinib is an effective treatment for RAF dimer-driven radioiodine-refractory differentiated thyroid cancer or anaplastic thyroid cancer. The researchers will also test whether avutometinib and defactinib is a safe treatment that causes few or mild side effects.
- Phase 2: a mid-size study of how well it works
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 18 and older
You may be able to join if
- Cohort A will enroll RAIR, R/M DTC patients with RAF dimer-driven disease. Cohort B will enroll ATC patients with RAF dimer-driven disease.
- Cohort A only: Patients must have pathologically or cytologically confirmed differentiated thyroid cancer of follicular origin (including papillary...
- Cohort B only: Patients must have anaplastic thyroid carcinoma.
- Confirmation in a CLIA certified laboratory that one of the patient's thyroid tumors (primary tumor, recurrent tumor, or metastases) possess at least...
- Cohort A only: Evidence of progressive disease (e.g. presence of new or growing lesion(s) on radiologic imaging and/or new or worsening tumor-related...
You likely can't join if
- Symptomatic untreated brain or leptomeningeal metastases Note: Patients with asymptomatic or treated brain or leptomeningeal metastases are allowed...
- Prior therapy with a MEK 1/2 inhibitor or an inhibitor that targets Class II/Class III BRAF alterations or a FAK inhibitor (with the exception of...
- Patient who have had systemic investigational anti-cancer therapy within 4 weeks of the first dose of study therapy.
- Major surgery within 4 weeks (excluding placement of vascular access), minor surgery within 2 weeks, or radiotherapy within 1 week of the first dose...
- Treatment with warfarin. Patients on warfarin for deep vein thrombosis/pulmonary embolism should be converted to low-molecular-weight heparin (LMWH)...
- Concomitant use of strong inhibitors and inducers of CYP3A4 (see Appendix 1 in Section 18). Patients should refrain from consumption of grapefruit...
See the full eligibility criteria
Who can join
- Cohort A will enroll RAIR, R/M DTC patients with RAF dimer-driven disease. Cohort B will enroll ATC patients with RAF dimer-driven disease.
- Cohort A only: Patients must have pathologically or cytologically confirmed differentiated thyroid cancer of follicular origin (including papillary thyroid carcinoma, follicular thyroid carcinoma, hurthle cell...
- Cohort B only: Patients must have anaplastic thyroid carcinoma.
- Confirmation in a CLIA certified laboratory that one of the patient's thyroid tumors (primary tumor, recurrent tumor, or metastases) possess at least one of the following genetic alterations: RAS mutation, NF1 mutation...
- Cohort A only: Evidence of progressive disease (e.g. presence of new or growing lesion(s) on radiologic imaging and/or new or worsening tumor-related symptoms) within 14 months of study enrollment.
- Cohort A only: Patients must have recurrent or metastatic disease not amenable to curative surgery or radiation.
- Patients with any number of prior therapies will be eligible.
- Patients must have RECIST v1.1 measurable disease.
- Age ≥ 18 years.
- ECOG performance status of 0 or 1.
- For Cohort A only: Patients must have not had recent treatment for thyroid cancer as defined as:
- No prior RAI therapy is allowed \<6 months prior to initiation of therapy on this protocol. A diagnostic study using \<10 mCi of RAI is not considered RAI therapy
- No external beam radiation therapy \<1 weeks prior to initiation of therapy on this protocol.
- No chemotherapy or targeted therapy (e.g., tyrosine kinase inhibitor) is allowed \<4 weeks prior to the initiation of therapy on this protocol
- For Cohort A only: Patients must have RAI-refractory disease, defined as one of the following:
- Total lifetime dose of radioiodine \> 600 mCi
- A tumor that is not radioiodine-avid on a diagnostic radioiodine scan performed
- A radioiodine-avid metastatic lesion which progressed despite radioiodine treatment given 6 months or more prior to study entry in the study. There are no size limitations for the index lesions used to satisfy this...
- The presence of at least one fluorodeoxyglucose (FDG) avid lesion.
- Patients must be able to swallow and retain orally-administered pills without any clinically significant gastrointestinal abnormalities that may alter absorption, such as malabsorption syndrome or major resection of the...
- Adequate recovery from toxicities related to prior treatments to at least Grade 1 by CTCAE v 5.0. Exceptions include alopecia and peripheral neuropathy grade ≤ 2.
- Patients must have tissue from the primary tumor or metastases available for correlative studies. Either a paraffin block or at least 20 unstained slides are acceptable (30 unstained slides would be ideal). (If less...
- Patients must agree to undergo two research biopsies of (a) malignant lesion(s). Tumor tissue obtained prior to study consent or treatment as part of standard of care can also be submitted in lieu of performance of the...
- Baseline QTc interval \< 460 ms for women and ≤450 ms for men using Frederica's QT correction formula. NOTE: This criterion does not apply to patients with a right or left bundle branch block.
- Adequate cardiac function wit left ventricular ejection fraction \>50% by echocardiography (ECHO) or multiple-gated acquisition (MUGA) scan.
- Screening laboratory values must meet the following criteria:
- WBC ≥ 2000/μL
- Neutrophils ≥ 1000/μL
- Platelets ≥ 100 x10\^3 /μL
- Hemoglobin \> 9.0 g/dL
- AST/ALT ≤ 2.5 x ULN (of \< 5x ULN in patients with liver metastases)
- Total Bilirubin ≤ 1.5 x ULN (except people with Gilbert Syndrome, who can have total bilirubin \< 3.0 mg/dL)
- International normalized ratio (INR) \< 1.5 and partial thromboplastin time (PTT) \< 1.5 x ULN in the absence of anticoagulation or therapeutic levels in the presence of anticoagulation.
- Albumin ≥ 3.0 g/dL (451 μmole/L)
- Creatine phosphokinase (CPK) ≤ 2.5 x ULN
- Serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 50 mL/min (if using the Cockcroft-Gault formula below)
- Female CrCl = (140 - age in years) x weight in kg x 0.85 72 x serum creatinine in mg/dL
- Male CrCl = (140 - age in years) x weight in kg x 1.00 72 x serum creatinine in mg/dL
What rules you out
- Symptomatic untreated brain or leptomeningeal metastases Note: Patients with asymptomatic or treated brain or leptomeningeal metastases are allowed. Participants with symptomatic brain or leptomeningeal metastases after...
- Prior therapy with a MEK 1/2 inhibitor or an inhibitor that targets Class II/Class III BRAF alterations or a FAK inhibitor (with the exception of patients who received these therapies for a defined period of time to...
- Patient who have had systemic investigational anti-cancer therapy within 4 weeks of the first dose of study therapy.
- Major surgery within 4 weeks (excluding placement of vascular access), minor surgery within 2 weeks, or radiotherapy within 1 week of the first dose of study drug.
- Treatment with warfarin. Patients on warfarin for deep vein thrombosis/pulmonary embolism should be converted to low-molecular-weight heparin (LMWH) or direct oral anticoagulants (DOACs).
- Concomitant use of strong inhibitors and inducers of CYP3A4 (see Appendix 1 in Section 18). Patients should refrain from consumption of grapefruit, grapefruit juice and St. John's Wort, and other medications (with or...
- Concomitant use of strong CYP2C9 inhibtors or inducers. For additional guidance see https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-druginteractions-table-substrates-inhibitors-and-inducers
- Concomitant use of strong P-glycoprotein(P-gp) inhibitors or inducers. For additional guidance see https://www.uptodate.com/contents/image/print?imageKey=EM%2F73326\&topicKey=HEME%2F1370\&source=outlinelink
- Patients with history of glaucoma, history of retinal vein occlusion (RVO), predisposing factors for RVO, including uncontrolled hypertension, uncontrolled diabetes.
- Patients with a history of retinal pathology or evidence of visible retinal pathology that is considered a risk factor for RVO, such as an intraocular pressure \> 21 mmHg
- Treatment-refractory hypertension defined as a blood pressure of systolic \>140 mmHg and/or diastolic \>90 mmHg which cannot be controlled by anti-hypertensive therapy.
- Patients with active hepatitis B infection (HBV surface antigen positive).
- Subject is known to be positive for Human Immunodeficiency Virus (HIV) or active Hepatitis C Virus (HCV). Testing for HIV or Hepatitis C prior to initiation of the study drug is not required. If a patient has a known...
- Known severe acute respiratory syndrome coronavirus 2 SARS-Cov2 infection (clinical symptoms) ≤28 days prior to first dose of study therapy.
- History of rhabdomyolysis.
- Concurrent congestive heart failure, prior history of class III/ IV cardiac disease (New York Heart Association [NYHA]), myocardial infarction within the last 6 months, unstable arrhythmias, unstable angina or severe...
- people with the inability to swallow oral medications or impaired gastrointestinal absorption due to gastrectomy or active inflammatory bowel disease
- Any other medical condition (e.g., cardiac, gastrointestinal, pulmonary, psychiatric, neurological, genetic, etc.) that in the opinion of the Investigator places the patient at unacceptably high risk for toxicity.
- Patients who are pregnant or breastfeeding.
- Patients with hypersensitivity to mannitol, magnesium stearate, HPMC (hydroxypropyl methylcellulose) shells
The study team makes the final eligibility decision.
Where it's taking place
- Basking Ridge, New Jersey, United States
- Middletown, New Jersey, United States
- Montvale, New Jersey, United States
- Commack, New York, United States
- Harrison, New York, United States
- New York, New York, United States
- Rockville Centre, New York, United States
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18 years and older. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Basking Ridge, New Jersey, United States; Middletown, New Jersey, United States; Montvale, New Jersey, United States; Commack, New York, United States; Harrison, New York, United States; New York, New York, United States and 1 more location(s). Enter your location above to see the nearest site and check your eligibility.
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BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.