| ClinicalTrials.gov Identifier |
| NCT06302621 |
| Institution Name |
| Massachusetts General Hospital |
| Institution City |
| Boston |
| Institution State |
| Massachusetts |
| Institution ZIP Code |
| 02114 |
| Institution Country |
| United States |
| Institution Phone |
| (617) 643-1765 |
| Institution Website |
| https://www.massgeneral.org/cancer-center/clinical-trials-and-research/termeer-center |
| Principal Investigator |
| Haley Ellis, MD |
| Principal Investigator Phone |
| (617) 724-4000 |
| Principal Investigator Email |
| hellis@mgh.harvard.edu |
| Additional Principal Investigators |
| Andreas Varkaris, MD |
| Study Coordinator |
| Susan Waddick, BS, RN OCN |
| Study Coordinator Phone |
| (617) 643-1765 |
| Study Coordinator Email |
| swaddick@mgh.harvard.edu |
| Study Overview |
| Studying the combination of pemigatinib and afatinib in patients with FGFR-altered advanced solid tumors, including cholangiocarcinoma. Preclinical work demonstrates this combination is effective in overcoming treatment resistance by blocking bypass growth pathways. Patients with and without prior FGFR inhibitor treatment are eligible. |
| Enrollment Information |
| 40 |
| Study Start Date |
| 20240401 |
| Study End Date |
| 20260401 |
| Study Purpose |
- Safety
- Tolerability
- Efficacy
|
| Exclusion Criteria |
- Unresectable or metastatic, histologically confirmed advanced solid tumor, where standard curative or palliative measures are no longer effective or are not considered appropriate/safe
- FGFR1-3 fusion, rearrangement, activating mutation, or FGFR2 extracellular domain in-frame deletions on tumor profiling
- Eastern Cooperative Oncology Group (ECOG) 0-1
- At least 18 years of age
- Ability to swallow tablets
- Life expectancy >/=3 months
- Ability to comply with outpatient treatment, laboratory monitoring, and required clinic visits for the duration of study participation
- Patients with cholangiocarcinoma must have adequate biliary drainage (per investigator’s discretion), with no evidence of ongoing infection
- Willingness of men and women of reproductive potential to observe conventional and effective birth control for the duration of treatment and for 3 months following the last dose of study treatment
- Measurable or non-measurable disease as determined by RECIST 1.1
- Adequate organ function
|
| Required Tests Prior to Study |
- For patients treated with a prior FGFR inhibitor, there is a list of excluded secondary FGFR2 kinase domain mutations. Please discuss with the study coordinator and PI.
- Systemic or liver-directed anticancer therapy within 2 weeks; or anticancer monoclonal antibody within 4 weeks prior to planned start of pemigatinib and afatinib
- Patient has adverse events from prior therapy that have not resolved to ≤ grade 1; exceptions for non-clinically meaningful AEs can be made with input from the principal investigator
- Major surgery within 4 weeks prior to planned start of pemigatinib and afatinib (tumor biopsy, biliary stent or catheter placement, and feeding tube placement are not considered major surgical procedures)
- Received prior palliative non-CNS radiation within 2 weeks or extended-field radiation administered within 4 weeks of first dose of study drug. Subjects must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. Fibrotic pulmonary disease from prior radiotherapy is permissible with approval of the study PI
- Known pre-existing interstitial lung disease
- Current hypovitaminosis D requiring supraphysiologic (eg 50,000 IU/weekly) to replenish the deficiency. Vitamin D supplements are allowed.
- History and/or current evidence of clinically significant ectopic mineralization/calcification or non-tumor related alteration of calcium-phosphorus homeostasis.
- History and/or current evidence of clinically significant corneal or retinal disorder confirmed by ophthalmological examination
- Child-Pugh B and C cirrhosis
- Chronic nausea, vomiting, or diarrhea considered to be clinically significant in the opinion of the investigator. This includes significant or recent gastrointestinal disorders with diarrhea as a major symptom.
- Clinically significant active malabsorption syndrome or other condition likely to affect gastrointestinal absorption of the study drug
- Patients with a history of another primary malignancy that is currently clinically significant, and has potential for metastases or currently requires active intervention (except for gonadotropin-releasing hormone (GnRH) or luteinizing hormone-releasing hormone (LH-RH) agonists in prostate cancer or hormonal therapy in breast cancer
- Have history of hepatic encephalopathy of any grade
- Active central nervous system (CNS) metastases are not eligible. Patients with asymptomatic and treated brain metastases may participate provided that they are stable for ≥ 2 months. Patients with suspected or confirmed leptomeningeal disease are not eligible even if treated. Patients with gliblastoma multiforme (GBM) are not eligible.
- Clinically significant, active cardiovascular disease such as uncontrolled hypertension, congestive heart failure NYHA classification of 3, unstable angina or poorly controlled arrhythmia, or history of myocardial infarction within 6 months prior to planned start of pemigatinib and afatinib
- Active uncontrolled systemic bacterial, viral, fungal or parasitic infection (except for fungal nail infection), or other clinically significant active disease process which in the opinion of the investigator and the sponsor-investigator makes it undesirable for the patient to participate in the trial. Screening for chronic conditions is not required.
|
| Potential Side Effects |
- Decreased appetite
- Diarrhea
- Dry eyes, mouth, nose, skin
- Eye issues, including blurry vision and retinal detachment (reversible)
- Fatigue
- Hair thinning or loss
- Hand-foot syndrome
- High phosphorus
- Mouth sores
- Nail and skin changes
- Nausea/vomiting
- Rash
- Taste changes
|
| Financial Assistance Available |
| No |
