Clinical trial NCT06332092: FID-007 and Cetuximab in Treating Patients With Advanced Head and Neck Squamous Cell Carcinoma
Official title: A Phase 2, Randomized, Multicenter, Open-label, Study of FID-007 in Combination With Cetuximab in Patients With Advanced Head and Neck Squamous Cell Carcinoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Head and Neck Squamous Cell Carcinoma
Keywords: FID-007
Cetuximab
Paclitaxel
Head and Neck
p16
Lead sponsor: Fulgent Pharma LLC.
Sponsor class: INDUSTRY
First posted: 2024-03-27
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: Two different dosing regimens of FID-007 in combination with fixed-dose Cetuximab
Primary purpose: TREATMENT

Brief summary: The goal of this FID-007 Clinical Trial is to compare the efficacy of different dosing regimens of FID-007 in combination with Cetuximab in patients with recurrent or metastatic Head and Neck Squamous Cell Carcinoma (HNSCC). The main questions it aims to answer are: to evaluate the efficacy, and to characterize the safety and tolerability. Eligible participants will be enrolled and randomized to 1 of 2 arms of FID-007 with fixed-dose Cetuximab in each 28-day cycle.

Detailed description: The goal of this FID-007 Randomized, Multicenter, Open-label clinical trial is to compare the efficacy of different dosing regimens of FID-007 in combination with Cetuximab in patients with recurrent or metastatic Head and Neck Squamous Cell Carcinoma (HNSCC) based on objective response rate. The main questions it aims to answer are:

* To evaluate the efficacy of different dosing regimens of FID-007 in combination with Cetuximab in patients based on Best Overall Response (BOR), Duration of Response (DoR), Disease Control Rate (DCR), Progression-Free Survival (PFS), and Overall Survival (OS).
* To characterize the pharmacokinetics (PK) of FID-007 and its metabolites (6-α-hydroxypaclitaxel and 3'-p-hydroxypaclitaxel) following administration of different dosing regimens of FID-007 in combination with Cetuximab in patients with recurrent or metastatic HNSCC.
* To characterize the safety and tolerability of different dosing regimens of FID-007 in combination with Cetuximab in patients.

Eligible participants will be enrolled and randomized to 1 of 2 arms of FID-007 with fixed-dose Cetuximab (starting from Cycle 2, 500 mg/m2 intravenous \[IV\] infusion every 2 weeks on Days 1 and 15 of each 28-day cycle). Patients will receive FID-007 via IV infusion over 30 minutes at their assigned dose on Days 1, 8, and 15 of each 28-day cycle.

Patients will continue to receive Cetuximab and FID-007 until they meet the study drug discontinuation criteria.

Eligibility criteria: Inclusion Criteria:

1. Ability to understand and willingness to provide informed consent before the start of any study-specific procedures.
2. Age ≥18 years old.
3. A diagnosis of recurrent or metastatic HNSCC at 1 of the following sites:

   1. Nasal/paranasal sinuses
   2. Nasopharynx (Epstein-Barr virus \[EBV\] negative only)
   3. Oral cavity
   4. Oropharynx
   5. Hypopharynx
   6. Larynx
4. Disease progression after treatment with PD-L1-based immune checkpoint inhibitor at any time. This can be as monotherapy or in combination with chemotherapy.
5. Measurable disease according to RECIST version 1.1.
6. Adequate treatment washout period of ≥21 days or 5 half-lives, whichever is shorter, for prior chemotherapy, radiotherapy, hormonal therapy, biological therapy, or immunotherapy before the first dose of study drug administration. Note: Palliative radiation is permitted but not ≤7 days before the first dose of study drug.
7. ECOG PS of 0 or 1.
8. Recovery from any toxic effects of previous chemotherapy, targeted therapy, or radiotherapy as judged by the investigator to Grade ≤1 (except for alopecia) according to NCI CTCAE version 5.0.
9. Adequate bone marrow and organ function defined as the following:

   Bone marrow function
   * Absolute neutrophil count ≥1500/mm3 (growth factor administration is not permitted ≤1 week before the screening assessment)
   * Platelet count ≥100,000/mm3 (platelet transfusion is not permitted ≤1 week before the screening assessment)
   * Hemoglobin ≥8 g/dL (criteria must be met without packed red blood cell transfusion ≤1 week before the screening assessment; chronic treatment with erythropoietin is permitted if the patient is on erythropoietin for ≥8 weeks)

   Blood clotting function

   • International normalized ratio (INR) ≤1.5 × upper limit of normal (ULN) and activated partial thromboplastin time ≤1.5 × ULN (except patients who are receiving therapeutic anticoagulation and whose INR should be within the therapeutic range)

   Renal function

   •Calculated clearance (using the Cockroft-Gault formula) ≥40 mL/min/1.73 m2. Actual body weight should be used for calculating creatinine clearance. For patients with a body mass index \>30 kg/m2, lean body weight should be used instead

   Hepatic function
   * Total bilirubin ≤1.5 × ULN (patients with Gilbert's disease can have bilirubin \>1.5 × ULN to \<3 × ULN)
   * Aspartate aminotransferase/alanine aminotransferase ≤3 × ULN
10. An estimated life expectancy of at least 3 months based on investigator judgment.
11. Negative serum pregnancy test result at screening for female patients of childbearing potential.
12. Willingness to abide by the contraceptive requirements in Appendix 1 of the protocol.

Exclusion Criteria:

1. Known hypersensitivity to paclitaxel.
2. EBV-positive nasopharyngeal cancer, sinonasal undifferentiated carcinoma, esthesioneuroblastoma, or squamous cell carcinoma of the salivary gland or skin, based on the patient's medical history.
3. Received \>1 prior line of anticancer therapy for recurrent or metastatic HNSCC. All patients must be previously treated with an immune checkpoint inhibitor either as monotherapy or in combination with chemotherapy. Patients treated with upfront combination chemo-immunotherapy followed by immunotherapy maintenance are considered to have received only 1 prior line of therapy. Chemotherapy given as part of treatment for locally advanced disease in the adjuvant or neoadjuvant setting is not considered a line of prior therapy for recurrent/metastatic disease. If the patient received prior treatment with Cetuximab, paclitaxel, or nab-paclitaxel in combination with radiation in the locally advanced setting and no relapse within 6 months of treatment discontinuation, enrollment is permitted if the treating physician believes that retreatment with Cetuximab or a taxane is a clinically reasonable option. However, patients who received these agents for recurrent or metastatic disease will be excluded.
4. Serious medical risk factors involving any of the major organ systems, or serious psychiatric disorders, that in the judgment of the investigator could compromise the patient's safety or the study data integrity.
5. Preexisting sensory neuropathy of Grade \>1 severity by NCI CTCAE version 5.0 criteria.
6. Known history of uncontrolled HIV infection defined as CD4+ cells \<350/mm3.
7. Requirement of systemic steroids at daily doses \>10 mg prednisone equivalent systemic exposure daily, including for control of symptoms.
8. Use of any CYP2C8 and CYP3A4 inhibitor (eg, ketoconazole and other imidazole antifungals, erythromycin, fluoxetine, gemfibrozil, cimetidine, ritonavir, saquinavir, indinavir, and nelfinavir) or inducer (eg, rifampicin, carbamazepine, phenytoin, efavirenz, and nevirapine) in the previous 14 days before the first dose of study drug until the last PK sample is obtained in the study.
9. Known brain metastasis. Note: Patients whose central nervous system metastases have been treated by surgery or radiotherapy, who are no longer on corticosteroids, and who are neurologically stable are eligible.
10. Current or recent participation in a study of an investigational product in the prior 4 weeks. Note: Patients who have completed the treatment phase of an investigational study and have entered the follow-up phase of the investigational study may participate in FID-007-003 as long as it has been ≥4 weeks before the first dose of study drug.
11. Pregnancy, breastfeeding, or plans to become pregnant during the study or within 24 weeks after the last dose of study drug (Appendix 1 of the protocol).
12. Plans to donate/bank or retrieve eggs (ova, oocytes) during the study or within 24 weeks after the last dose of study drug (Appendix 1 of the protocol).

Primary outcomes:
measure: ORR assessed by Response Evaluation Criteria in Solid Tumors (RECIST)
timeFrame: Through study completion, an average of 1 year
Secondary outcomes:
measure: BOR assessed by Response Evaluation Criteria in Solid Tumors (RECIST)
timeFrame: Through study completion, an average of 1 year
measure: Duration of Response (DoR) measurement
timeFrame: Through study completion, an average of 1 year
measure: Progression-free Survival (PFS) measurement
timeFrame: Through study completion, an average of 1 year
measure: Overall Survival (OS) measurement
timeFrame: Through study completion, an average of 1 year
measure: Disease Control Rate (DCR) analysis
timeFrame: Through study completion, an average of 1 year
measure: Adverse Events (AEs) graded according to the CTCAE version 5.0
timeFrame: Through study completion, an average of 1 year
measure: Vital Signs safety assessments
timeFrame: Through study completion, an average of 1 year
measure: Clinical Laboratory safety assessments
timeFrame: Through study completion, an average of 1 year
measure: ECGs safety assessment
timeFrame: Through study completion, an average of 1 year
measure: Area Under the Plasma Concentration Versus Time Curve (AUC) of FID-007
timeFrame: Cycle 2 (each cycle is 28 days)
measure: Peak Plasma Concentration (Cmax)
timeFrame: Cycle 2 (each cycle is 28 days)
measure: Terminal/elimination half-life (t1/2)
timeFrame: Cycle 2 (each cycle is 28 days)
measure: Clearance (CL)
timeFrame: Cycle 2 (each cycle is 28 days)
measure: Volume of Distribution (Vd)
timeFrame: Cycle 2 (each cycle is 28 days)
Other outcomes:
Locations:
city: Fayetteville
country: United States
facility: Highlands Oncology - North Hills
state: Arkansas
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center and Hospital
state: California
city: Tampa
country: United States
facility: Moffitt Cancer Center Magnolia Campus
state: Florida
city: Fort Wayne
country: United States
facility: Fort Wayne Medical Oncology and Hematology
state: Indiana
city: Dallas
country: United States
facility: Texas Oncology - Baylor Charles A. Sammons Cancer Center
state: Texas
city: Tyler
country: United States
facility: Texas Oncology - Northeast Texas Cancer & Research Institute
state: Texas
Study officials:
affiliation: Fulgent Pharma LLC.
name: Fulgent Clinical Sites
role: PRINCIPAL_INVESTIGATOR
References:
citation: Barsouk A, Aluru JS, Rawla P, Saginala K, Barsouk A. Epidemiology, Risk Factors, and Prevention of Head and Neck Squamous Cell Carcinoma. Med Sci (Basel). 2023 Jun 13;11(2):42. doi: 10.3390/medsci11020042.
citation: Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209-249. doi: 10.3322/caac.21660. Epub 2021 Feb 4.
citation: Burtness B, Rischin D, Greil R, Soulieres D, Tahara M, de Castro G Jr, Psyrri A, Brana I, Baste N, Neupane P, Bratland A, Fuereder T, Hughes BGM, Mesia R, Ngamphaiboon N, Rordorf T, Wan Ishak WZ, Ge J, Swaby RF, Gumuscu B, Harrington K. Pembrolizumab Alone or With Chemotherapy for Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma in KEYNOTE-048: Subgroup Analysis by Programmed Death Ligand-1 Combined Positive Score. J Clin Oncol. 2022 Jul 20;40(21):2321-2332. doi: 10.1200/JCO.21.02198. Epub 2022 Mar 25.
citation: Burtness B, Goldwasser MA, Flood W, Mattar B, Forastiere AA; Eastern Cooperative Oncology Group. Phase III randomized trial of cisplatin plus placebo compared with cisplatin plus cetuximab in metastatic/recurrent head and neck cancer: an Eastern Cooperative Oncology Group study. J Clin Oncol. 2005 Dec 1;23(34):8646-54. doi: 10.1200/JCO.2005.02.4646.
citation: Vermorken JB, Mesia R, Rivera F, Remenar E, Kawecki A, Rottey S, Erfan J, Zabolotnyy D, Kienzer HR, Cupissol D, Peyrade F, Benasso M, Vynnychenko I, De Raucourt D, Bokemeyer C, Schueler A, Amellal N, Hitt R. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med. 2008 Sep 11;359(11):1116-27. doi: 10.1056/NEJMoa0802656.
citation: Vermorken JB, Trigo J, Hitt R, Koralewski P, Diaz-Rubio E, Rolland F, Knecht R, Amellal N, Schueler A, Baselga J. Open-label, uncontrolled, multicenter phase II study to evaluate the efficacy and toxicity of cetuximab as a single agent in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck who failed to respond to platinum-based therapy. J Clin Oncol. 2007 Jun 1;25(16):2171-7. doi: 10.1200/JCO.2006.06.7447.
citation: Fury MG, Sherman E, Lisa D, Agarwal N, Algazy K, Brockstein B, Langer C, Lim D, Mehra R, Rajan SK, Korte S, Lipson B, Yunus F, Tanvetyanon T, Smith-Marrone S, Ng K, Xiao H, Haque S, Pfister DG. A randomized phase II study of cetuximab every 2 weeks at either 500 or 750 mg/m2 for patients with recurrent or metastatic head and neck squamous cell cancer. J Natl Compr Canc Netw. 2012 Nov 1;10(11):1391-8. doi: 10.6004/jnccn.2012.0144.
citation: Herbst RS, Kelly K, Chansky K, Mack PC, Franklin WA, Hirsch FR, Atkins JN, Dakhil SR, Albain KS, Kim ES, Redman M, Crowley JJ, Gandara DR. Phase II selection design trial of concurrent chemotherapy and cetuximab versus chemotherapy followed by cetuximab in advanced-stage non-small-cell lung cancer: Southwest Oncology Group study S0342. J Clin Oncol. 2010 Nov 1;28(31):4747-54. doi: 10.1200/JCO.2009.27.9356. Epub 2010 Oct 4.
citation: Jain RK. Transport of molecules in the tumor interstitium: a review. Cancer Res. 1987 Jun 15;47(12):3039-51.
citation: Baban DF, Seymour LW. Control of tumour vascular permeability. Adv Drug Deliv Rev. 1998 Oct 5;34(1):109-119. doi: 10.1016/s0169-409x(98)00003-9.
citation: Serpe L. Conventional chemotherapeutic drug nanoparticles for cancer treatment. Kumar CS, ed. Nanomaterials for Cancer Therapy. Vol 6. Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim; 2006:1-39.
citation: Desai N, Trieu V, Yao Z, Louie L, Ci S, Yang A, Tao C, De T, Beals B, Dykes D, Noker P, Yao R, Labao E, Hawkins M, Soon-Shiong P. Increased antitumor activity, intratumor paclitaxel concentrations, and endothelial cell transport of cremophor-free, albumin-bound paclitaxel, ABI-007, compared with cremophor-based paclitaxel. Clin Cancer Res. 2006 Feb 15;12(4):1317-24. doi: 10.1158/1078-0432.CCR-05-1634.
citation: Grau JJ, Caballero M, Verger E, Monzo M, Blanch JL. Weekly paclitaxel for platin-resistant stage IV head and neck cancer patients. Acta Otolaryngol. 2009 Nov;129(11):1294-9. doi: 10.3109/00016480802590451.
citation: Gibson MK, Li Y, Murphy B, Hussain MH, DeConti RC, Ensley J, Forastiere AA; Eastern Cooperative Oncology Group. Randomized phase III evaluation of cisplatin plus fluorouracil versus cisplatin plus paclitaxel in advanced head and neck cancer (E1395): an intergroup trial of the Eastern Cooperative Oncology Group. J Clin Oncol. 2005 May 20;23(15):3562-7. doi: 10.1200/JCO.2005.01.057.
citation: Maghami E, Ismaila N, Alvarez A, Chernock R, Duvvuri U, Geiger J, Gross N, Haughey B, Paul D, Rodriguez C, Sher D, Stambuk HE, Waldron J, Witek M, Caudell J. Diagnosis and Management of Squamous Cell Carcinoma of Unknown Primary in the Head and Neck: ASCO Guideline. J Clin Oncol. 2020 Aug 1;38(22):2570-2596. doi: 10.1200/JCO.20.00275. Epub 2020 Apr 23.
citation: Functional Assessment of Chronic Illness Therapy (FACIT) Group. Functional Assessment of Cancer Therapy - Head & Neck (FACT-HN), Version 4. Accessed September 12, 2023. https://www.facit.org/measures/FACT-HN
citation: [HMA] Heads of Medicines Agencies. Clinical Trial Facilitation Group page. Recommendations related to contraception and pregnancy testing in clinical trials. September 15, 2014. Accessed October 12, 2023. http://www.hma.eu/fileadmin/dateien/Human_Medicines/01-About_HMA/Working_Groups/CTFG/2014_09_HMA_CTFG_Contraception.pdf
citation: Yin R, Cheng T-C, Durst HD, Qin D. Enhancing Protein Activity through Nanoencapsulation. US Patent 6, 716, 450. 06-Apr-2004.
citation: Yin R, Durst HD, Emanuel PA, Hagnauer GL. Compositions and methods for enhancing bioassay performance through nanomanipulation. US Patent 6,773,928. August 10, 2004.
citation: Fulgent Pharma LLC. Investigator's Brochure for FID-007. Version 6. Fulgent Pharma, LLC; 2017.
citation: Erbitux- Cetuximab solution. Prescribing information. ImClone LLC; Revised: September 2021. https://uspl.lilly.com/erbitux/erbitux.html#pi