0C-14-7: A Phase 1/2A, Multicenter, Open-Label Study of Oral RxDx-101 in Adult Patients with Locally Advanced or Metastatic Cancer Confirmed to be Positive for TRKA, TRKB, TRKC, ROS1, or ALK Molecular Alterations
Detailed DescriptionRXDX-101-01 is a multicenter, open-label, Phase 1/2a study in which the safety and efficacy of RXDX-101 will be evaluated in adult patients with any locally advanced or metastatic solid tumor. The primary objective of the Phase 2a expansion cohorts is Objective Response (OR) defined as Complete Response(CR) and Partial Response (PR) at the recommended phase 2 dose of RXDX-101. RXDX-101 is an orally available inhibitor of the tyrosine kinases TrkA, TrkB, TrkC, ROS1, and ALK. Molecular alterations to these targets are present in several different tumor types, including non-small cell lung cancer, colorectal cancer, papillary thyroid cancer, pancreatic cancer, and neuroblastoma. The Phase 2a segment of this study will consist of 5 cohorts as described below: Cohort #1: Participants that express TrkA. Cohort #2: Participants that express TrkB. Cohort #3: Participants that express TrkC. Cohort #4a: Participants that express ALK with an associated molecular alteration who are nave to prior treatment with ALK inhibitors. Cohort #4b: Participants that express ALK with an associated molecular alteration who have received prior treatment with one or more ALK inhibitors. Cohort #5: Participants that express ROS1 USC will only participate in Phase 2 of the study. The length of participation is about 2 months An End of Treatment Visit will be conducted within 7 days of last dose of RXDX-101. A Safety Follow-Up telephone call will be conducted approximately 30 days following the last dose of RXDX-101. Primary endpoint will be first cycle dose limiting toxicities and maximum tolerated dose The baseline, clinical outcome, laboratory, PK, and safety data from both segments of the study will be analyzed descriptively
Inclusion and Exclusion Criteria
- Histologically or cytologically confirmed diagnosis of locally advanced or metastatic solid tumors that have a TrkA, TrkB, TrkC, ROS1, or ALK molecular alteration.
- Measurable disease according to RECIST version 1.1.
- Prior cancer therapy is allowed, including crizotinib and investigational drugs. At the time of treatment start, at least 2-4 weeks must have elapsed after prior cytotoxic chemotherapy (at least 6 weeks for nitrosureas, mitomycin C and liposomal doxorubicin). In the absence of toxicity, 7 days must have elapsed since completion of prior non-cytotoxic cancer therapy.
- Prior radiotherapy is allowed if >14 days have elapsed since end of treatment, provided that no more than 25% of bone marrow reserve has been irradiated.
- Patients with controlled asymptomatic central nervous system involvement are allowed in absence of therapy with anticonvulsants.
- Patients who have received brain irradiation must have completed whole brain radiotherapy and gamma knife at least 4 weeks prior to enrollment.
- Resolution of all acute toxic effects (excluding alopecia) of any prior anti-cancer therapy to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Grade less than or equal to 1.
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2.
- Adult patients age 18 years or older.
- Life expectancy of at least 3 months.
- Current participation in another therapeutic clinical trial.
- Known symptomatic brain metastases or leptomeningeal involvement as assessed by MRI or contrast CT scan examination.
- History of previous cancer, except squamous cell or basal-cell carcinoma of the skin, or any in situ carcinoma that has been completely resected, requiring therapy within the previous 3 years.
- Incomplete recovery from any surgery prior to treatment.
- Any of the following in the past 6 months: myocardial infarction, unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosis.
- History of prolonged QTc interval (e.g., repeated demonstration of a QTc interval > 450 milliseconds).
- History of additional risk factors for torsade de pointes (e.g., heart failure, family history of long QT syndrome).
- Use of concomitant medications that increase or possibly increase the risk to prolong the QTc interval and/or induce torsades de pointes ventricular arrhythmia.
- Known active infections (bacterial, fungal, viral including HIV positivity).
- Gastrointestinal disease (e.g., Crohn's disease, ulcerative colitis, or short gut syndrome) or other malabsorption syndromes that would impact on drug absorption.
- Known interstitial lung disease, interstitial fibrosis, or history of tyrosine kinase inhibitor-induced pneumonitis.
- Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient inappropriate for entry into this study or could compromise protocol objectives in the opinion of the Investigator and/or the Sponsor.
Please contact Poornima Murali to learn more about where you can participate in this trial. Please use the contact form on the right side.