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

NCT04849377 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: GCO 21-0525
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

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

Keywords

Loco Regional Control (LRC); Risk-based De-intensified chemoradio therapy (CRT)

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (4)

Group I - 50 Gy/200 mg/m2

EXPERIMENTAL

Patient Characteristics: \<20 Pack-Years, HPV16, OP, T1,T2 N0 RT 5 days per week for 6 weeks and Cisplatin weekly for 5 weeks

Radiation: RT 50 Gy; Drug: Cisplatin 200

Group II - 54 Gy/200mg/m2

EXPERIMENTAL

Patient Characteristics: \<20 Pack-Years, HPV16, OP, T1-T2, N1-N2b, T3 N0-N2b RT 5 days per week for 6 weeks and Cisplatin weekly for 6 weeks

Radiation: RT 54 GY; Drug: Cisplatin 200

Group III - 60 Gy/240 mg/m2

EXPERIMENTAL

Patient Characteristics: 20-40 Pack-Years, Non-HPV16, Non-OP, T1-T2, N1-N2b, T3 N0-N2b RT 5 days per week for 6 weeks and Cisplatin weekly for 6 weeks

Radiation: RT 60 GY; Drug: Cisplatin 240

Group IV - TPF Induction followed by 60 Gy and Carboplatin AUC 1.5

EXPERIMENTAL

Patient Characteristics: 20-40 Pack-Years, Non-HPV16, Non-OP, T4, N2c, \>3 nodes, ENE, or Matted Nodes Induction Therapy: Cisplatin, Docetaxel, Fluorouracil followed by RT 60 GY + Carboplatin AUC 9.0 Docetaxel every 21 days for 3 cycles, Cisplatin every 21 days for 3 cycles, Fluorouracil continuous infusion over 4 days (every 21 days for 3 cycles). Followed by RT 5 days per week for 6 weeks and Carboplatin weekly for 6 weeks.

Radiation: RT 60 GY; Other: Induction Therapy; Drug: Carboplatin; Drug: Cisplatin 240

Interventions

RT 50 Gy RADIATION

Radiation Therapy (RT) 50 GY

Also known as: Radiation Therapy

Group I - 50 Gy/200 mg/m2

RT 54 GY RADIATION

Radiation Therapy (RT) 54 GY

Also known as: Radiation Therapy

Group II - 54 Gy/200mg/m2

RT 60 GY RADIATION

Radiation Therapy (RT) 60 GY

Also known as: Radiation Therapy

Group III - 60 Gy/240 mg/m2; Group IV - TPF Induction followed by 60 Gy and Carboplatin AUC 1.5

Induction Therapy OTHER

Induction Therapy: Cisplatin, Docetaxel, Fluorouracil

Group IV - TPF Induction followed by 60 Gy and Carboplatin AUC 1.5

Carboplatin DRUG

Carboplatin AUC 9.0

Group IV - TPF Induction followed by 60 Gy and Carboplatin AUC 1.5

Cisplatin 200 DRUG

200 mg/m2

Group I - 50 Gy/200 mg/m2; Group II - 54 Gy/200mg/m2

Cisplatin 240 DRUG

240mg/m2

Group III - 60 Gy/240 mg/m2; Group IV - TPF Induction followed by 60 Gy and Carboplatin AUC 1.5

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically-confirmed squamous cell carcinoma of the head and neck, including subsites of the oropharynx, hypopharynx, larynx, and nasopharynx (with data on EBV)
• 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
• HPV positivity by PCR assessed with either tissue or cytology in the central laboratory
• Stages I, II, III, or IV according to the AJCC 7th edition without evidence of distant metastases
• Age \> 18
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• 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
• Adequate renal function as defined by a creatinine clearance \> 60 ml/min (actual or calculated by the Cockcroft-Gault equation)
• 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
• A negative pregnancy test within 7 days of starting therapy in women of childbearing potential

You may not qualify if:

• Women who are currently pregnant or breast-feeding
• Men or women of childbearing potential who are not using adequate contraception during treatment and at least 3 months after therapy
• 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)
• Radiation therapy for prior malignancy (except radioactive iodine for thyroid cancer)
• Prior chemotherapy for other malignancy or autoimmune disease
• Metastatic disease at presentation
• Nasal cavity subsite
• 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
• Prior radiation therapy or chemotherapy for HNSCC (prior surgery alone is permitted)
• Active substance use disorder (ETOH or drugs, excluding marijuana)
• Prior use of IV drugs
• Significant peripheral neuropathy (\> grade 2 according to NCI CTC)
• Prior hematologic or solid organ transplant
• Major medical comorbidity including:
• Significant cardiovascular disease.

Sponsors & Collaborators

• Icahn School of Medicine at Mount Sinai: lead

Study Sites (1)

Mount Sinai Hospital

New York, New York, 10029, United States

Location

Related Publications (15)

• 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. doi: 10.1056/NEJMoa065497.

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• Carlander AF, Gronhoj Larsen C, Jensen DH, Garnaes E, Kiss K, Andersen L, Olsen CH, Franzmann M, Hogdall E, Kjaer 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.

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• 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.

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• 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.

  PMID: 20451455 BACKGROUND

• 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.

  PMID: 20587061 BACKGROUND

• 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.

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• 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.

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• 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.

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• 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.

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• 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. doi: 10.1093/jnci/djh183.

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• 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.

  PMID: 19289615 BACKGROUND

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

Radiotherapy; Neoadjuvant Therapy; Carboplatin

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Therapeutics; Combined Modality Therapy; Coordination Complexes; Organic Chemicals

Study Officials

• Marshall Posner, MD

  Ichan School of Medicine at Mount Sinai Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Model Details: CRT (Cisplatin with IMRT/IMPT): Group I 50 Gy/200 mg/m2, Group II 54 Gy/200 mg/m2, Group III 60 Gy/240 mg/m2 Sequential Therapy: Group IV TPF Induction followed by 60 Gy and Carboplatin AUC 1.5

Study Record Dates

• First Submitted: April 14, 2021
• First Posted: April 19, 2021
• Study Start: June 14, 2022
• Primary Completion: June 14, 2022
• Study Completion: June 14, 2022
• Last Updated: July 7, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)