Weekly Cetuximab/RT Versus Weekly Cisplatin/RT in HPV-Associated Oropharyngeal Squamous Cell Carcinoma

NCT01855451 | Unknown Phase 3 DMC

• 2 other identifiers: TROG 12.01ACTRN12613000279729
• Study Type: interventional
• Target: 189
• Locations: 2 countries
• Sites: 16

Brief Summary

A standard treatment for patients with head and neck cancer is radiation given with high doses of a chemotherapy drug called cisplatin, given every 3 weeks during the radiation. This treatment is effective but can significantly increase side effects such as difficulty with swallowing, a sore mouth, fatigue, hearing loss, ringing in the ears and kidney failure. In Australia, a commonly used treatment HPV-Associated Oropharyngeal Squamous Cell Carcinoma is a lower dose of cisplatin given weekly during the radiation. The high dose and low dose schedules result in a similar total dose of cisplatin being given during the radiation, but it is thought that the weekly schedule results in fewer side effects while maintaining effectiveness. Another approach widely used around the world for patients with head and neck cancer, is to administer the antibody, cetuximab, weekly during radiation. Cetuximab has a very different side effect profile to cisplatin, and has been reported to result in less exacerbation of radiation related side effects. Both cetuximab and cisplatin can reduce the growth of a cancer and increase the effectiveness of radiation. Both cisplatin and cetuximab appear to be effective treatments in combination with radiation, but have not been directly compared. The purpose of this study is to compare the treatment related side effects (both acute and longer term) between the cisplatin and cetuximab regimens. Both treatments would be given with the same dose of radiation therapy over 7 weeks. The results of this trial will help determine the optimal treatment for patients with HPV-Associated Oropharyngeal Squamous Cell Carcinoma.

Conditions

HPV Positive Oropharyngeal Squamous Cell Carcinoma

Keywords

Human Papilloma Virus; HPV; Oropharyngeal; Squamous Cell; Carcinoma

Outcome Measures

Primary Outcomes (1)

• Symptom Severity

  The area under curve of symptom severity between weekly cisplatin and Radiotherapy Therapy (RT) versus weekly cetuximab and RT from baseline to week 20 (13 weeks post-completion of radiotherapy) as measured by M.D. Anderson Symptom Inventory - Head and Neck Module (MDASI-HN).

  20 weeks

Secondary Outcomes (17)

• Symptom severity

  24 months

• Interference of symptoms with daily life

  24 mths

• Psychological distress

  36 months

• Impact on Health Related Quality of Life

  36 months

• Swallowing dysfunction

  12 months

Study Arms (2)

Radiation Therapy + Cetuximab

ACTIVE COMPARATOR

RT (70 Gy in 35 fractions, 5 days a week over 7 weeks) with weekly Cetuximab (400 mg/m2 loading dose IV prior to radiation, followed by weekly cetuximab 250 mg/m2 for the duration of the radiotherapy)

Drug: Cetuximab; Radiation: RT (70 Gy in 35 fractions)

Radiation Therapy + Cisplatin

ACTIVE COMPARATOR

RT(70 Gy in 35 fractions, 5 days a week over 7 weeks) with weekly Cisplatin (40 mg/m2 IV for the duration of the radiotherapy)

Radiation: RT (70 Gy in 35 fractions); Drug: Cisplatin

Interventions

Cetuximab DRUG

Radiation Therapy + Cetuximab

RT (70 Gy in 35 fractions) RADIATION

Radiation Therapy + Cetuximab; Radiation Therapy + Cisplatin

Cisplatin DRUG

Radiation Therapy + Cisplatin

Eligibility Criteria

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

You may qualify if:

• Aged 18 years or older
• Has provided written Informed Consent for participation in this trial
• Histologically confirmed squamous cell carcinoma of the oropharynx with p16 positive status confirmed locally by immunohistochemistry
• Stage III (excluding T1-2N1) or stage IV (excluding T4, N3, and distant metastasis) if smoking history of \< /=10 pack years. If \> 10 pack years nodal disease must be N0 - N2a.
• If an excisional biopsy has been performed, patients remain eligible for the study provided there is clinically measurable disease prior to commencing RT. The residual disease should still meet the stage criteria required for the trial e.g. excisional biopsy of a node with residual T3 primary, or tonsillectomy for T1 primary with residual \> N2a nodes.
• No prior treatment for oropharyngeal cancer
• Adequate haematological, renal, and hepatic function as defined by,
• Absolute neutrophil count (ANC, segs + bands) \> /= 1.5 x 109/L
• Platelet count \> /= 100 x 109/L
• Total bilirubin \< /= 1.5 x upper normal limit
• ALT \< /= 2.5 x upper normal limit
• Calculated creatinine clearance (Cockcroft-Gault formula) or isotopic GFR \> 55ml/min
• ECOG performance status score of 0-1
• Participants capable of childbearing are using adequate contraception and intend to continue use of contraception for at least 6 months following completion of treatment
• Negative pregnancy test within 72 hours prior to randomisation of women who are of childbearing potential

You may not qualify if:

• History of unknown primary of the head and neck
• T4, N3 or distant metastases
• Smoking history \>10 pack years with N2b or c nodal status
• Women who are pregnant or lactating.
• Previous radiotherapy to the area to be treated (excluding superficial radiotherapy for a cutaneous malignancy)
• Previous cisplatin or carboplatin chemotherapy
• Prior EGFR targeted therapy of any kind
• Primary surgery to the affected area (excisional biopsy allowed)
• Peripheral neuropathy \> /= grade 2 (CTCAE v4.0)
• Tinnitus \> /= grade 2 (CTCAE v4.0)
• History of interstitial lung disease or evidence of interstitial lung disease on pre-registration CT
• History of myocardial infarction within 12 months prior to study entry, uncontrolled congestive heart failure, unstable angina, active cardiomyopathy, unstable arrhythmia, uncontrolled psychotic disorders, active serious infections, active peptic ulcer disease, immunosuppression due to post-organ transplantation or use of immunosuppressants for autoimmune disorders
• Patients known to be HIV positive
• Other cancer that was diagnosed:
• more than 5 years prior to current diagnosis with (i) subsequent evidence of disease recurrence or (ii) clinical expectation of recurrence is greater than 10% or

Sponsors & Collaborators

• Trans Tasman Radiation Oncology Group: lead

Study Sites (16)

Canberra Hospital

Canberra, Australian Capital Territory, Australia

Location

Chris O'Brien Lifehouse

Camperdown, New South Wales, 2050, Australia

Location

Liverpool Hospital

Liverpool, New South Wales, 2170, Australia

Location

St George Hospital

Saint George, New South Wales, 2217, Australia

Location

Riverina Cancer Care Centre

Wagga Wagga, New South Wales, Australia

Location

Calvary Mater Newcastle

Waratah, New South Wales, Australia

Location

Westmead Hospital

Westmead, New South Wales, 2145, Australia

Location

Royal Brisbane and Womens Hospital

Herston, Queensland, 4006, Australia

Location

Townsville Hospital

Townsville, Queensland, 4810, Australia

Location

Princess Alexandra Hospital

Woolloongabba, Queensland, 4102, Australia

Location

Flinders Medical Centre

Bedford Park, South Australia, 5042, Australia

Location

Peter MacCallum Cancer Centre

East Melbourne, Victoria, 3002, Australia

Location

Austin Hospital

Melbourne N., Victoria, 3084, Australia

Location

Sir Charles Gairdner

Nedlands, Western Australia, 6009, Australia

Location

Auckland City Hospital

Auckland, 1344, New Zealand

Location

Palmerston North Hospital

Palmerston, 4442, New Zealand

Location

Related Publications (1)

• Rischin D, King M, Kenny L, Porceddu S, Wratten C, Macann A, Jackson JE, Bressel M, Herschtal A, Fisher R, Fua T, Lin C, Liu C, Hughes BGM, McGrath M, McDowell L, Corry J. Randomized Trial of Radiation Therapy With Weekly Cisplatin or Cetuximab in Low-Risk HPV-Associated Oropharyngeal Cancer (TROG 12.01) - A Trans-Tasman Radiation Oncology Group Study. Int J Radiat Oncol Biol Phys. 2021 Nov 15;111(4):876-886. doi: 10.1016/j.ijrobp.2021.04.015. Epub 2021 Jun 4.

  PMID: 34098030 DERIVED

MeSH Terms

Conditions

Carcinoma

Interventions

Cetuximab; Cisplatin

Condition Hierarchy (Ancestors)

Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• D Rischin, Dr

  TROG and Peter MacCallum Cancer Centre

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 13, 2013
• First Posted: May 16, 2013
• Study Start: June 3, 2013
• Primary Completion: April 30, 2020
• Study Completion: August 23, 2023
• Last Updated: November 18, 2022

Record last verified: 2022-11

Locations

AU (14); NZ (2)