A Phase 3, Multicenter, Randomized, Open-Label, Study Evaluating the Efficacy and Safety of Nanvuranlat in Patients with Previously Treated Advanced Biliary Tract Cancer
| ClinicalTrials.gov Identifier |
| NCT07265674 |
| Institution Name |
| Memorial Sloan Kettering Cancer Center |
| Full Institution Address |
|
1275 York Avenue New York NY 10065 United States |
| Institution Phone |
| 332-266-1798 |
| Institution Website |
| https://www.mskcc.org/cancer-care/doctors/ghassan-abou-alfa#contact-and-location |
| Additional Institutions |
|
University of California at Irvine Orange, CA The University of Texas MD Anderson Cancer Center Houston, TX Rutgers Cancer Institute of New Jersey New Brunswick, NJ University of Texas Southwestern Medical Center Dallas, TX NYC Health + Hospitals/Bellevue (Bellevue Hospital Center) New York, NY Banner MD Anderson Cancer Center Gilbert, AZ City of Hope Duarte, CA Karmanos Cancer Institute Detroit, MI Mercy Clinic Women's Oncology - Chub O'Reilly Cancer Center (St. John’s Clinic – Women’s Oncology) Oklahoma City, OK University Hospitals Cleveland Medical Center Cleveland, OH Henry Ford Health Detroit, MI Roswell Park Comprehensive Cancer Center Buffalo, NY Norton Cancer Institute- Audubon Louisville, KY University of Minnesota- Masonic Cancer Center Minneapolis, MN UCLA Medical Center Santa Monica, CA The Ohio State University Comprehensive Cancer Center Columbus, OH Ochsner Medical Center (OMC) New Orleans, LA Allegheny Health Network Pittsburgh, PA Fred Hutchinson Cancer Center Clinic - South Lake Union (Outpatient Clinic) Seattle, Washington Moffitt Cancer Center Magnolia Campus Tampa, FL Comprehensive Cancer Centers of Nevada (CCCN) - Central Valley Las Vegas, NV For the current site list and contact information, please see https://clinicaltrials.gov/study/NCT07265674 |
| Principal Investigator |
| Ghassan Abou-Alfa |
| Principal Investigator Phone |
| 646-598-4788 |
| Principal Investigator Email |
| abou-alg@mskcc.org |
| Additional Principal Investigators |
|
Farshid Dayyani, University of California at Irvine, fdayyani@hs.uci.edu, 714-456-8000 Milind Javle, The University of Texas MD Anderson Cancer Center, mjavle@mdanderson.org, 713-792-2828 Stacey Stein, Rutgers Cancer Institute of New Jersey, sms@cinj.rutgers.edu, 732-235-5912 David Hsieh, University of Texas Southwestern Medical Center, david.hsieh@UTSouthwestern.edu, 214-645-9685 Jennifer Wu, NYC Health + Hospitals/Bellevue (Bellevue Hospital Center), jennifer.wu@nyulangone.org, 212-263-3809 Madappa Kundranda, Banner MD Anderson Cancer Center, madappa.kundranda@bannerhealth.com, 480-256-6444 Gagandeep Brar, City of Hope, gbrar@coh.org, 626-218-9200 Wasif Saif, Karmanos Cancer Institute, saifw@karmanos.org 313-576-8706 Carla Kurkjian, Mercy Clinic Women's Oncology - Chub O'Reilly Cancer Center (St. John’s Clinic – Women’s Oncology), carla.kurkjian@mercy.net, 405-732-3402 Amit Mahipal, University Hospitals Cleveland Medical Center, amit.mahipal@uhhospitals.org, 216-844-6031 Maria Diab, Henry Ford Health, mdiab2@hfhs.org, 888-734-5322 Kannan Thanikachalam, Roswell Park Comprehensive Cancer Center, kannan.thanikachalam@roswellpark.org Michael Driscoll, Norton Cancer Institute- Audubon, michael.driscoll@nortonhealthcare.org, 502-636-7845 Ajay Prakash, University of Minnesota- Masonic Cancer Center, M Health Fairview, praka086@umn.edu, 612-626-5906 Saeed Sadeghi, UCLA Medical Center, ssadeghi@mednet.ucla.edu, 310-829-5471 Anne Noonan, The Ohio State University Comprehensive Cancer Center, anne.noonan@osumc.edu Jonathan Mizrahi, Ochsner Medical Center (OMC), jonathan.mizrahi@ochsner.org, 504-842-3910 Nathan Bahary, Allegheny Health Network, Nathan.Bahary@ahn.org, 412-359-8379 Gentry King, Fred Hutchinson Cancer Center Clinic - South Lake Union (Outpatient Clinic), gking@fredhutch.org2, 206-606-6230 Richard Kim, Moffitt Cancer Center Magnolia Campus, richard.kim@moffitt.org Fadi Braiteh, Comprehensive Cancer Centers of Nevada (CCCN) - Central Valley, fadi.braiteh@usoncology.com, 702-952-3400 For the current site list and contact information, please see https://clinicaltrials.gov/study/NCT07265674 |
| Study Coordinator |
| Amin Yaqubie |
| Study Coordinator Phone |
| 646-888-4327 |
| Study Coordinator Email |
| yaqubiea@mskcc.org |
| Additional Study Coordinators |
| For the current site list and contact information, please see https://clinicaltrials.gov/study/NCT07265674 |
| Study Overview |
| This study has two main goals: to find the best dose of nanvuranlat and to compare it with standard treatments for adults with bile duct cancer. In Part A, participants will be randomly assigned to one of four groups: three different nanvuranlat dose levels or the doctor’s choice of standard treatment. In Part B, participants will be randomly assigned to either nanvuranlat or standard treatment. Everyone will receive treatment every two weeks and will continue as long as it remains safe, effective, and appropriate. To monitor safety, participants will have regular checkups, including physical exams, vital signs, ECGs, and lab tests. Scans will track how the cancer responds, and the study will also evaluate biological markers to better understand how nanvuranlat works. |
| Enrollment Information |
| Part A-120, Part B-360 |
| Study Start Date |
| 20260116 |
| Study End Date |
| 20271001 |
| Study Purpose |
|
This study is being conducted to learn more about an investigational (experimental) medication called nanvuranlat. In this study, the researchers will evaluate the safety of nanvuranlat; how well it works against cancer; and also how it behaves, is processed, and is eliminated in the body (often called “pharmacokinetics” or “PK”). The study will also explore how genetic differences affect how nanvuranlat behaves in the body. The study includes 2 parts. You will participate in either Part A or Part B. The main purpose of Part A is to choose a dose of nanvuranlat to study in Part B. The main purpose of Part B is to look at how cancer responds in people taking nanvuranlat compared with people taking other types of chemotherapy and also people not taking any medications to treat their cancer. |
| Inclusion Criteria |
|
1. At least 18 years of age inclusive at the time of signing the informed consent. 2. Provides informed written consent according to local laws or regulations. 3. Able and willing to comply with scheduled visits, treatment plans, procedures, and laboratory tests, including peripheral blood and urine sampling during the study. 4. Willing to participate in LAT1 testing and NAT2 and transporter genotyping. Note: For LAT1 testing, if the participant does not have archival tissue and a fresh biopsy is not in the best interest of the participant, they will still be eligible for the trial. 5. Cancer must be metastatic, locally advanced and unresectable, or not amenable to treatment with local therapies that could offer a reasonable likelihood of clinical benefit. 6. Histologic or cytologic diagnosis of BTC. 7. Has BTC that is classified as either an IHC, EHC, or GBC based on surgical, clinical, or laparoscopic findings and/or radiological imaging (eg, CT, MRI). 8. Has received 1 prior appropriate platinum (cisplatin, carboplatin, or oxaliplatin)-based therapy for advanced disease (locally advanced or metastatic) with or without a mAb targeting PD-1 or PD-L1. Disease progression during or within 6 months of neoadjuvant or adjuvant treatment with a platinum-containing regimen will count as having received 1 prior regimen. If a patient has a mutation/fusion of IDH1, FGFR2 or NTRK, or an amplified, mutated, or overexpressed form of HER2, or a recognized aberration in a validated "driver" of BTC, and was treated with an appropriate targeted agent, or the patient's tumor was determined to be MSI-H and an appropriate PD-1/PD-L1 mAb was administered, the targeted therapy or immunotherapy will NOT count as a separate line of treatment. 9. ECOG PS of 0 or 1. 10. Expected life expectancy of at least 90 days after the first day of treatment as per the site Investigator. 11. At least 1 measurable lesion by RECIST v1.1 based on imaging (eg, CT, MRI) performed within 28 days prior to initiation of study intervention. Those who have received prior local therapy, including but not limited to embolization, chemoembolization, radiation therapy, and/or other appropriate ablative procedures to a measurable lesion that is within the treatment and shown ≥ 20% growth in size since posttreatment assessment. 12. Resolution to ≤ Grade 1 by the NCI CTCAE v 5.0 (or higher) of all clinically significant toxic effects of prior chemotherapy or other treatments, except for alopecia and peripheral neuropathy (these must have resolved to ≤ Grade 2). If medical therapy is required for the treatment of a laboratory abnormality, the dose and laboratory value(s) should be stable. 13. Adequate hematologic function: ANC ≥ 1.5 × 109/L. Myeloid growth factors must not have been administered within 7 days before the participant's first dose of study intervention. Hemoglobin ≥ 8.5 g/dL and no RBC transfusions during the 14 days before the participant's first dose of study intervention. Platelet count ≥ 100 × 109/L and no platelet transfusions during the 14 days before the participant's first dose of study intervention. 14. Adequate baseline organ function, as demonstrated by the following: eGFR ≥ 50 mL/min as estimated by CKD-EPI 2021. Bilirubin ≤ 2 × ULN (local institution). AST and ALT ≤ 5 × ULN (local institution). 15. Adequate coagulation function as defined by INR ≤ 1.5 OR a PT ≤ 1.5 × ULN AND an aPTT ≤ 1.5 × ULN if not receiving anticoagulation therapy. Note: Participants may receive subtherapeutic doses of warfarin while on study to maintain patency of venous devices but not with therapeutic doses of warfarin. Participants may be treated with low-molecular weight heparin. 16. Women of childbearing potential must be willing to use a highly effective method of contraception throughout the study and study follow up or for at least 9 months after the last dose of study intervention. Note: A woman is of nonchildbearing potential if she meets 1 of the following criteria: a) postmenopausal with at least 12 months of spontaneous amenorrhea; b) has had a bilateral oophorectomy; or c) has had a hysterectomy. Highly effective methods of contraception include: 17. Abstinence from sexual activity. Hormonal contraception (eg, injection, implant, pill, patch, or vaginal ring as available in each country) associated with inhibition of ovulation (both estrogen and progestogen and progestogen only) in use for at least 30 days before administration of study intervention. Intrauterine device in use for at least 30 days before administration of study intervention. Intrauterine hormone-releasing system in use for at least 30 days before administration of study intervention. Bilateral tubal occlusion/ligation at least 6 months before administration of study intervention. Partner who has been vasectomized at least 6 months before administration of study intervention. Males and their female partners must use a highly effective method of birth control if female partner(s) is of childbearing potential, and males must not donate sperm during the study and for 9 months after the last dose of study intervention. |
| Exclusion Criteria |
|
1. Received systemic therapy or an investigational agent before washing out, as follows: < 2 weeks prior to Cycle 1 Day 1 for systemic non-immune-based therapy < 3 weeks prior to Cycle 1 Day 1 for immune-based therapy ≤ 5 half-lives or 3 weeks (whichever is longer) prior to Cycle 1 Day 1 for an investigational agent 2. Received radiotherapy to metastatic sites within 2 weeks of Cycle 1 Day 1. Patients must have recovered from all radiation-related toxicities and not require corticosteroids. A 1 week washout is permitted for palliative radiation with a limited port ≤ 2 weeks of radiotherapy to non-CNS disease. 3. Underwent hepatic radiation, chemoembolization, or radiofrequency ablation < 4 weeks prior to Cycle 1 Day 1. 4. Underwent major surgery < 3 weeks before Screening and has not recovered adequately from the procedure and/or any complications from the surgery prior to starting study intervention. 5. Known active CNS metastases and/or carcinomatous meningitis. Those with previously treated brain metastases may participate provided they are radiologically stable (ie, without evidence of PD for at least 4 weeks by repeat imaging), clinically stable, and without requirement of corticosteroid treatment for at least 14 days prior to first dose of study intervention. For those with a history of CNS involvement, repeat imaging should be performed during study screening. However, CNS imaging is not required prior to study entry unless there is clinical suspicion of CNS involvement. 6. Clinically significant cardiovascular disease (eg, uncontrolled or any New York Heart Association Class 3 or 4 heart failure, uncontrolled angina, history of myocardial infarction, unstable angina, or stroke within 6 months prior to study entry, uncontrolled hypertension or clinically significant arrhythmias not controlled by medication). 7. Resting QTcF > 470 msec at screening. 8. An additional active malignancy that is progressing or has required active treatment within the past 3 years. Cases involving a past cancer history with substantial potential for recurrence must be discussed with the Medical Monitor before study entry. Patients with the following concomitant neoplastic diagnoses are eligible: non-melanoma skin cancer, carcinoma in situ (including transitional cell carcinoma, cervical intraepithelial neoplasia, breast cancer, and melanoma in situ), organ-confined prostate cancer with no evidence of PD. 9. Require strong inhibitors of P-gp, BCRP, OATP1B1, OATP1B3, OATP1A2, and OAT3 transporters unless they can be transferred to other medications within ≥ 5 half-lives of treatment. 10. Require sensitive substrates of OATP1B1 and OATP1B3 unless they can be transferred to other medications within ≥ 5 half-lives of treatment. 11. Known positive status for HIV, has not been treated with established appropriate antiretroviral therapy for at least 4 weeks, and has a hydrophobic interaction chromatography viral load < 400 copies/mL and a CD4+ T-cell (CD4+) counts ≥ 350 cells/µL prior to enrollment. No HIV testing is required unless mandated by local health authority. 12. Active or chronic HBV and active (not cured) HCV. Participants who are HBV carriers without active disease (HBV DNA titer < 1000 copies/mL or 200 IU/mL) or cured HCV (negative HCV RNA test) with confirmed viral clearance that are not receiving ongoing treatment and without residual chronic liver disease may be enrolled. 13. An uncontrolled intercurrent illness including, but not limited to medical illness; uncontrolled infection requiring therapy; psychiatric illness; alcohol or drug dependence; social situations or a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating Investigator or Medical Monitor. 14. Requires therapeutic doses of warfarin (ie, requires monitoring). A washout period of 7 days before administration of a participant's first dose of study intervention is required for those in whom therapeutic doses of warfarin are discontinued. Note: Warfarin at a low daily dose to maintain patency for indwelling venous catheters is allowed. Low-molecular weight heparin and direct-acting oral anticoagulants, according to the inclusion requirements pertaining to coagulation test results, are allowed. 15. Clinically significant edema or intracavitary fluid collections (eg, ascites, pleural effusion, pericardial effusions) resulting in moderate symptoms and/or requiring frequent drainage. 16. Previously developed shock, anaphylaxis, or renal disorder due to SBECD. 17. WOCBP who is pregnant, lactating, or discontinued lactation < 12 weeks prior to Screening, or who plans to become pregnant or initiate lactation during the study. 18. Known reaction or contraindication to any component of study intervention (ie, oxaliplatin, leucovorin [including levoleucovorin], and 5-FU [FOLFOX] and irinotecan, leucovorin, and 5-FU [FOLFIRI]). 19. Known DPD deficiency. Screening for DPD deficiency is not mandated but should be considered in subjects who have had severe toxicity due to fluoropyrimidine-based therapy in the past. |
| Required Tests Prior to Study |
| Blood draws, urinalysis, fresh tumor biopsy (if archival tissue is not available), 12-lead ECG |
| Potential Side Effects |
|
Nanvuranlat has been administered to cancer patients in 2 studies. In the first study, 17 patients with various types of advanced forms of cancer received nanvuranlat. Common side effects (those reported by more than one patient) included general discomfort (17.6%), nausea, fever, elevated liver function tests, and high blood pressure (11.8% each). In the second study, 70 patients with advanced forms of biliary tract cancer (bile duct cancer) received nanvuranlat. Side effects reported by more than 5% patients included general discomfort (11.4%), decreased appetite (10.0%), diarrhea (7.1%), and fever (5.7%). |
| Financial Assistance Available |
| Yes |