RBD-HPV: Risk-Based De-Intensification for HPV+ HNSCC

Head and Neck Squamous Cell Carcinoma (HNSCC) Clinical Trial

Official title:

RBD-HPV: Risk-Based De-Intensification for HPV+ HNSCC

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04849377
• Other study ID #: GCO 21-0525
• Status: Withdrawn
• Phase: Phase 2
• Start date: June 14, 2022
• Est. completion date: June 14, 2022

Study information

• Verified date: July 2022
• Source: Icahn School of Medicine at Mount Sinai
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this research study is to determine the rate of local regional control at 2 years when using de-intensified chemoradiotherapy (CRT) in patients with Human Papillomavirus (HPV)-associated head and neck squamous cell carcinoma (HNSCC). Local regional control means no recurrence of the cancer in the head or neck area. Study subjects will be enrolled into 4 groups. Group/treatment will be based on a number of factors, including smoking and drinking history.

Description:

The purpose of this research study is to determine the rate of local regional control at 2 years when using de-intensified chemoradiotherapy (CRT) in patients with Human Papillomavirus (HPV)-associated head and neck squamous cell carcinoma (HNSCC). Local regional control means no recurrence of the cancer in the head or neck area. Study subjects will be enrolled into 4 groups. Group/treatment will be based on a number of factors, including smoking and drinking history.

If participants choose to participate, participants will be asked to:

• Participate in screening for eligibility, this will include: questions regarding \medical history, physical exam, blood/urine samples, electrocardiogram, PET/CT and/or CT-MRI of the neck, assessment of tumor, and a questionnaire.

• Complete the study regimen including evaluations and follow up visits. Participants may be in this research study for approximately to 5 years after receiving standard of care (SOC) treatment. Depending on the group enrolled in, the treatment will last either 6 weeks (Groups 1-3) or 15 weeks (Group 4.This group will also receive 3 cycles of SOC induction therapy (One cycle = 21 days). Induction therapy is initial chemotherapy delivered prior to radiation or surgery when treating cancer.

• Participate in routine types of procedures such as clinical exams, blood and urine tests, and imaging tests to assess tumor.

• Consent to storage of research samples.

This research study involves chemotherapy and intensity-modulated radiation therapy (IMRT) IMRT is used to safely deliver precise radiation to a tumor while minimizing the dose to surrounding normal tissue.

There are no added costs associated with participation. There is no reimbursement for participation.

The names of the drugs/interventions involved in this study are:

• Cisplatin

• Docetaxel (Group 4 only)

• Fluorouracil (Group 4 only)

• Carboplatin (Group 4 Only)

All of the drugs listed above are approved for use by the Food and Drug Administration (FDA), commercially available, and considered standard of care (SOC) for cancer.

Serious known side effects that participants may experience include:

• Nausea and vomiting

• Diarrhea

• Fever

• Skin irritation, rash

• Joint pain

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: June 14, 2022
• Est. primary completion date: June 14, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria: Patients must meet the following inclusion criteria to be eligible for enrollment in RBD-HPV:

1. Histologically-confirmed squamous cell carcinoma of the head and neck, including subsites of the oropharynx, hypopharynx, larynx, and nasopharynx (with data on EBV)

2. P16+ positivity as measured by IHC in a lab that is verified by the central laboratory or if the slides are available for review by the central laboratory

3. HPV positivity by PCR assessed with either tissue or cytology in the central laboratory

4. Stages I, II, III, or IV according to the AJCC 7th edition without evidence of distant metastases

5. Age > 18

6. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

7. Adequate marrow function as defined by the following parameters:

• Neutrophil count > 1.5 x 109/l

• Platelet count > 100 x 109/l

• Hemoglobin > 10 g/dl

8. Adequate renal function as defined by a creatinine clearance > 60 ml/min (actual or calculated by the Cockcroft-Gault equation)

9. Adequate liver function as defined by the following parameters:

• Total bilirubin < institutional upper limit of normal (ULN) (except patients with Gilbert's Syndrome who have no other liver disease or abnormal liver serologies)

• AST or ALT and alkaline phosphatase within the ranges described below

10. A negative pregnancy test within 7 days of starting therapy in women of childbearing potential

11. Capacity to understand the study protocol

12. Willingness to provide written consent.

Exclusion Criteria: Patients will not be eligible for enrollment in this study if they exhibit any of the following conditions:

1. Women who are currently pregnant or breast-feeding

2. Men or women of childbearing potential who are not using adequate contraception during treatment and at least 3 months after therapy

3. Current or prior malignancy in the last 5 years (excluding basal or squamous cell carcinoma of the skin not requiring systemic or radiation therapies, or prostate CA that is well-controlled and observed, etc)

4. Radiation therapy for prior malignancy (except radioactive iodine for thyroid cancer)

5. Prior chemotherapy for other malignancy or autoimmune disease

6. Metastatic disease at presentation

7. Nasal cavity subsite

8. Active smoking (defined as > 1 cigarette per day within the last five years) or former smoking (has to have quit > 10 years ago) with a cumulative pack year history > 40 pack years

9. Prior radiation therapy or chemotherapy for HNSCC (prior surgery alone is permitted)

10. Active substance use disorder (ETOH or drugs, excluding marijuana)

11. Prior use of IV drugs

12. Significant peripheral neuropathy (> grade 2 according to NCI CTC)

13. Prior hematologic or solid organ transplant

14. Major medical comorbidity including:

• Significant cardiovascular disease.

• Significant neurologic disorder, including dementia and seizures.

• Significant psychiatric disorder.

• Active infection that is uncontrolled.

• PUD (peptic ulcer disease) that is clinically active or unhealed.

• Hypercalcemia.

• COPD with hospitalization in the last 12 months for pneumonia or respiratory failure.

• Interstitial lung disease.

• Autoimmune disease requiring therapy.

• Uncontrolled HIV infection (not on HAART, CD4 < 200).

• Active Hepatitis C (+ RNA).

15. Enrollment in a therapeutic clinical trial within 30 days of study entry

16. Concurrent treatment with any other antineoplastic therapy

17. Significant weight loss (> 25% of TBW) in the 2 months prior to study entry

18. Patient has a history of non-adherence to medical care

19. Patient will not be able to engage in comprehensive follow-up at Mount Sinai.

Related Conditions & MeSH terms

• Head and Neck Squamous Cell Carcinoma (HNSCC)
• Human Papillomavirus (HPV)
• Squamous Cell Carcinoma of Head and Neck

Intervention

Radiation:
• RT 50 Gy
Radiation Therapy (RT) 50 GY
• RT 54 GY
Radiation Therapy (RT) 54 GY
• RT 60 GY
Radiation Therapy (RT) 60 GY

Other:
• Induction Therapy
Induction Therapy: Cisplatin, Docetaxel, Fluorouracil

Drug:
• Carboplatin
Carboplatin AUC 9.0
• Cisplatin 200
200 mg/m2
• Cisplatin 240
240mg/m2

Locations

Country	Name	City	State
United States	Mount Sinai Hospital	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Icahn School of Medicine at Mount Sinai

Country where clinical trial is conducted

United States, 

References & Publications (15)

Braakhuis BJ, Snijders PJ, Keune WJ, Meijer CJ, Ruijter-Schippers HJ, Leemans CR, Brakenhoff RH. Genetic patterns in head and neck cancers that contain or lack transcriptionally active human papillomavirus. J Natl Cancer Inst. 2004 Jul 7;96(13):998-1006. — View Citation

Carlander AF, Grønhøj Larsen C, Jensen DH, Garnæs E, Kiss K, Andersen L, Olsen CH, Franzmann M, Høgdall E, Kjær SK, Norrild B, Specht L, Andersen E, van Overeem Hansen T, Nielsen FC, von Buchwald C. Continuing rise in oropharyngeal cancer in a high HPV prevalence area: A Danish population-based study from 2011 to 2014. Eur J Cancer. 2017 Jan;70:75-82. doi: 10.1016/j.ejca.2016.10.015. Epub 2016 Nov 23. — View Citation

Chaturvedi AK, Anderson WF, Lortet-Tieulent J, Curado MP, Ferlay J, Franceschi S, Rosenberg PS, Bray F, Gillison ML. Worldwide trends in incidence rates for oral cavity and oropharyngeal cancers. J Clin Oncol. 2013 Dec 20;31(36):4550-9. doi: 10.1200/JCO.2013.50.3870. Epub 2013 Nov 18. — View Citation

Chaturvedi AK, Engels EA, Pfeiffer RM, Hernandez BY, Xiao W, Kim E, Jiang B, Goodman MT, Sibug-Saber M, Cozen W, Liu L, Lynch CF, Wentzensen N, Jordan RC, Altekruse S, Anderson WF, Rosenberg PS, Gillison ML. Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol. 2011 Nov 10;29(32):4294-301. doi: 10.1200/JCO.2011.36.4596. Epub 2011 Oct 3. — View Citation

D'Souza G, Kreimer AR, Viscidi R, Pawlita M, Fakhry C, Koch WM, Westra WH, Gillison ML. Case-control study of human papillomavirus and oropharyngeal cancer. N Engl J Med. 2007 May 10;356(19):1944-56. — View Citation

Dayyani F, Etzel CJ, Liu M, Ho CH, Lippman SM, Tsao AS. Meta-analysis of the impact of human papillomavirus (HPV) on cancer risk and overall survival in head and neck squamous cell carcinomas (HNSCC). Head Neck Oncol. 2010 Jun 29;2:15. doi: 10.1186/1758-3284-2-15. Review. — View Citation

Fakhry C, Westra WH, Li S, Cmelak A, Ridge JA, Pinto H, Forastiere A, Gillison ML. Improved survival of patients with human papillomavirus-positive head and neck squamous cell carcinoma in a prospective clinical trial. J Natl Cancer Inst. 2008 Feb 20;100(4):261-9. doi: 10.1093/jnci/djn011. Epub 2008 Feb 12. — View Citation

Gillison ML, Chaturvedi AK, Anderson WF, Fakhry C. Epidemiology of Human Papillomavirus-Positive Head and Neck Squamous Cell Carcinoma. J Clin Oncol. 2015 Oct 10;33(29):3235-42. doi: 10.1200/JCO.2015.61.6995. Epub 2015 Sep 8. Review. — View Citation

Gillison ML, D'Souza G, Westra W, Sugar E, Xiao W, Begum S, Viscidi R. Distinct risk factor profiles for human papillomavirus type 16-positive and human papillomavirus type 16-negative head and neck cancers. J Natl Cancer Inst. 2008 Mar 19;100(6):407-20. doi: 10.1093/jnci/djn025. Epub 2008 Mar 11. — View Citation

Klussmann JP, Mooren JJ, Lehnen M, Claessen SM, Stenner M, Huebbers CU, Weissenborn SJ, Wedemeyer I, Preuss SF, Straetmans JM, Manni JJ, Hopman AH, Speel EJ. Genetic signatures of HPV-related and unrelated oropharyngeal carcinoma and their prognostic implications. Clin Cancer Res. 2009 Mar 1;15(5):1779-86. doi: 10.1158/1078-0432.CCR-08-1463. Epub 2009 Feb 17. — View Citation

Lassen P, Eriksen JG, Hamilton-Dutoit S, Tramm T, Alsner J, Overgaard J. Effect of HPV-associated p16INK4A expression on response to radiotherapy and survival in squamous cell carcinoma of the head and neck. J Clin Oncol. 2009 Apr 20;27(12):1992-8. doi: 10.1200/JCO.2008.20.2853. Epub 2009 Mar 16. — View Citation

Marur S, D'Souza G, Westra WH, Forastiere AA. HPV-associated head and neck cancer: a virus-related cancer epidemic. Lancet Oncol. 2010 Aug;11(8):781-9. doi: 10.1016/S1470-2045(10)70017-6. Epub 2010 May 5. Review. — View Citation

Mork J, Lie AK, Glattre E, Hallmans G, Jellum E, Koskela P, Møller B, Pukkala E, Schiller JT, Youngman L, Lehtinen M, Dillner J. Human papillomavirus infection as a risk factor for squamous-cell carcinoma of the head and neck. N Engl J Med. 2001 Apr 12;344(15):1125-31. — View Citation

Seiwert TY, Zuo Z, Keck MK, Khattri A, Pedamallu CS, Stricker T, Brown C, Pugh TJ, Stojanov P, Cho J, Lawrence MS, Getz G, Brägelmann J, DeBoer R, Weichselbaum RR, Langerman A, Portugal L, Blair E, Stenson K, Lingen MW, Cohen EE, Vokes EE, White KP, Hammerman PS. Integrative and comparative genomic analysis of HPV-positive and HPV-negative head and neck squamous cell carcinomas. Clin Cancer Res. 2015 Feb 1;21(3):632-41. doi: 10.1158/1078-0432.CCR-13-3310. Epub 2014 Jul 23. — View Citation

Westra WH, Taube JM, Poeta ML, Begum S, Sidransky D, Koch WM. Inverse relationship between human papillomavirus-16 infection and disruptive p53 gene mutations in squamous cell carcinoma of the head and neck. Clin Cancer Res. 2008 Jan 15;14(2):366-9. doi: 10.1158/1078-0432.CCR-07-1402. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of Locoregional control (LRC)	The rate of locoregional control (LRC) at 2 years - Local regional control means no recurrence of the cancer in the head or neck area.	2 years