Risk-Directed Postoperative Radiation Therapy and Cisplatin for the Treatment of Stage I-II HPV-Related Oropharynx Squamous Cell Carcinoma, The Minimalist Trial-2 (MINT-2)

Status: active

This phase II trial tests how well giving risk-directed radiation therapy and chemotherapy after surgery works for the treatment of patients with stage I-II human papillomavirus virus (HPV)-related oropharynx squamous cell carcinoma. The current standard practice after surgery is to treat patients with both radiation and a drug called cisplatin. Cisplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of tumor cells. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill tumor cells and shrink tumors. In this trial, patients are assessed for the risk of the cancer returning after surgery. Using patient risk to give a lower dose of radiation therapy and less cisplatin or no cisplatin at all may be able to reduce the occurrence and severity of the associated side effects, while not increasing the chances the disease will come back.

Inclusion Criteria

Histologically or cytologically confirmed HPV-related, clinical stages I-II oropharyngeal squamous cell carcinoma (OPSCC) (8th edition of American Joint Committee on Cancer [AJCC]/Union for International Cancer Control [UICC] Staging Manual) or HPV-related neck node with unknown primary. Clinical T1N0M0 and T2N0M0 disease are excluded. HPV-related may be defined by p16 immunohistochemistry (IHC) stain and/or HPV-High Risk ribonucleic acid (RNA) in situ hybridization (ISH)/HPV deoxyribonucleic acid (DNA) genotyping by polymerase chain reaction (PCR), using standard definitions of positive and negative test results.
Planned resection of the primary tumor site by a transoral approach (transoral robotic surgery [TORS], transoral laser microsurgery [TLM], or conventional surgery)
Planned unilateral or contralateral selective neck dissection
Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2
Creatinine clearance ≥ 50 mL/min
Absolute neutrophil count (ANC) ≥ 1.0 K/cumm
Platelet count ≥ 100 K/cumm
At least 18 years of age
Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately
Ability to understand and willingness to sign an Institutional Review Board (IRB) approved written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants

Exclusion Criteria

Clinical T1N0M0 or T2N0M0 disease
Prior radiation therapy for head and neck squamous cell carcinoma (HNSCC)
Planned free-flap reconstruction of the resected primary site
Cirrhosis with Child-Pugh score B or C
History of prior invasive malignancy diagnosed within 2 years prior to study enrollment; exceptions are malignancies with a low risk of metastasis or death (e.g., expected 5-year OS > 90%) that were treated with curative-intent therapy
Receiving any other investigational agents
Uncontrolled serious inter-current illness or serious psychiatric illness/social situations that would limit compliance with study requirements
Pregnant and/or breastfeeding. A negative serum or urine pregnancy test is required at screening for all female patients of childbearing potential

PRIMARY OBJECTIVE:

I. To determine the 2-year recurrence rate for each arm.

SECONDARY OBJECTIVES:

I. To determine the mean percent weight loss during radiation therapy (RT) in each arm, starting at day 1 of RT and ending on the last day of RT.

II. To evaluate the proportion of patients in each arm who underwent percutaneous endoscopic gastrostomy (PEG) tube placement before RT, during RT, or after RT but within 6 weeks of completion of RT.

III. To determine the duration of need for an indwelling PEG tube (in patients who required one).

IV. To evaluate the proportion of patients in each arm taking narcotics before RT, during RT, or at 6 weeks after completion of RT.

V. To determine the adverse event (AE) profile from the day of surgery until the day before RT and during and after RT in each arm.

VI. To determine the mean change in serum creatinine during RT in each arm, starting at day 1 of RT and ending on the last day of RT.

VII. To determine the progression-free survival (PFS) and overall survival (OS) for each arm.

TERTIARY/EXPLORATORY OBJECTIVES:

I. To document the measures of Quality of Life (QOL) at baseline, during treatment, and through two years after completion of treatment in each arm.

II. To document the proportion of patients with tumor tissue modified viral (TTMV) detected on NavDx Assay at baseline that become undetectable at 4 months after completion of radiation therapy, along with the HPV genotypes detected.

OUTLINE:

Patients undergo surgical tumor resection on study. Following surgery, patients determined to have high-risk disease are assigned to Arm 1, while patients with intermediate-risk disease are randomized to Arm 2A, 2B, or 2C. Patients with the highest- and lowest-risk disease after surgery do not continue study treatment.

ARM 1: Within 28 - 56 days after resection, patients undergo intensity-modulated radiation therapy (IMRT) or intensity-modulated proton therapy (IMPT) once daily (QD) Monday-Friday, with one day of twice daily (BID) treatment, for a total of 21 treatment fractions in the absence of disease progression or unacceptable toxicity. Patients also receive cisplatin intravenously (IV) over 60 minutes once on one of the first 5 days of radiation therapy on study. Additionally, patients undergo laryngoscopy at baseline, as well as computed tomography (CT), fludeoxyglucose-positron emission tomography (FDG-PET)/CT and collection of blood samples throughout the study.

ARM 2A: Within 28 - 56 days after resection, patients undergo IMRT or IMPT QD Monday-Friday, with one day of BID treatment, for a total of 21 treatment fractions in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo laryngoscopy at baseline, as well as CT, FDG-PET/CT and collection of blood samples throughout the study.

ARM 2B: Within 28 - 56 days after resection, patients undergo a lower dose of IMRT or IMPT QD Monday-Friday, with one day of BID treatment, for a total of 21 treatment fractions in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo laryngoscopy at baseline, as well as CT, FDG-PET/CT and collection of blood samples throughout the study.

ARM 2C: Within 28 - 56 days after resection, patients undergo the lowest dose of IMRT or IMPT QD Monday-Friday, with one day of BID treatment, for a total of 15 treatment fractions in the absence of disease progression or unacceptable toxicity. Patients also receive cisplatin IV over 60 minutes once on one of the first 5 days of radiation therapy on study. Additionally, patients undergo laryngoscopy at baseline, as well as CT, FDG-PET/CT and collection of blood samples throughout the study.

After completion of study treatment, patients are followed up at 6 weeks, and then at 4, 6, 12, 18, 24, 36, 48, and 60 months.

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Risk-Directed Postoperative Radiation Therapy and Cisplatin for the Treatment of Stage I-II HPV-Related Oropharynx Squamous Cell Carcinoma, The Minimalist Trial-2 (MINT-2)

Inclusion Criteria

Exclusion Criteria

United States

Missouri

Saint Louis

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Risk-Directed Postoperative Radiation Therapy and Cisplatin for the Treatment of Stage I-II HPV-Related Oropharynx Squamous Cell Carcinoma, The Minimalist Trial-2 (MINT-2)

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