Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT05119036 |
| Other study ID # |
OTHN-CC-IUSCCC-0756 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
Phase 2
|
| First received |
|
| Last updated |
|
| Start date |
May 12, 2022 |
| Est. completion date |
December 31, 2026 |
Study information
| Verified date |
August 2023 |
| Source |
Indiana University |
| Contact |
Leila Partoo |
| Phone |
317-278-1286 |
| Email |
lpartoo[@]iu.edu |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Oropharyngeal squamous cell carcinoma (OPSCC), commonly known as throat cancer or tonsil
cancer, has seen a dramatic rise in incidence over the last twenty years. There are two types
of OPSCC: human papillomavirus-positive (HPV+) and human papillomavirus-negative (HPV-).
People with OPSCC, regardless of their type, typically receive standard treatment with a
combination of chemotherapy, radiation therapy, and surgery. Due to the intensity of standard
treatment, survivors may experience unwanted long-term side effects. The goal of this
research study is to see if intensifying (stopping or scaling back) treatment still provides
the same, or perhaps even better, results when compared to standard treatment.
Description:
Oropharyngeal squamous cell carcinoma (OPSCC) has seen a dramatic rise in incidence over the
last two decades. This is largely due to the increased incidence of human
papillomavirus-positive (HPV+) malignancy within the oropharynx. In fact, HPV-positive (HPV+)
OPSCC has surpassed cervical cancer as the most common HPV related malignancy in the United
States. Thus, with the current widespread prevalence of HPV infection, OPSCC will continue to
be a major factor in cancer treatment in the national healthcare landscape for years to come.
Fortunately, patients with HPV+ OPSCC have substantially improved treatment response and
overall survival (OS) compared to those with HPV-negative malignancy. Prior surgical
procedures to remove tumors within the oropharynx were very invasive and highly morbid,
requiring face and neck incisions along with mandibulotomy and pharyngotomy approaches.
Therefore, treatment paradigms shifted to favor concurrent chemoradiation as the primary
treatment modality over primary surgery. However, the acute and long-term toxicity of
chemoradiation can be significant, including swallow dysfunction, speech disturbance, taste
disturbance, mucositis, xerostomia, fibrosis, osteoradionecrosis, neutropenia, neurotoxicity,
and dental disease. With improved survival rates associated with HPV+ OPSCC, more patients
are surviving their disease and experiencing these side effects, negatively impacting quality
of life (QOL).
With early studies establishing the more favorable prognosis associated with HPV+ OPSCC9, the
staging system for OPSCC was completely changed, with HPV+ OPSCC given its own separate
system from its HPV negative counterpart. Even with higher nodal burden, HPV+ OPSCC has lower
stages, reflecting improved treatment response of this disease. Notably, this
reclassification omitted extranodal extension (ENE) as a component of the N staging.
The advent of transoral robotic surgery (TORS) via the da Vinci Surgical System, and other
minimally invasive techniques, has reaffirmed surgical therapy as a primary treatment option,
as these approaches provide quicker recovery times and confer less morbidity to patients. The
safety and oncologic efficacy of TORS has been well-established for the treatment of OPSCC.
For example, in one large multi-institutional study of 410 patients undergoing TORS, the
2-year locoregional control rate was 91.8%, disease-specific survival rate 94.5%, and overall
survival 91%13. Now, the majority of patients undergo surgery for T1-T2 disease (82%) in the
United States according to an analysis of the National Cancer Data Base.
The goal of primary surgical therapy is to minimize long term toxicity by eliminating the
need for chemotherapy, decreasing radiation intensity to adjuvant doses, and in some cases,
obviating the need for adjuvant therapy altogether while still providing equivalent or even
superior oncologic results compared to standard chemoradiation. The resulting effects are
improvement in functional outcomes and QOL for patients surviving their disease. The
prevailing treatment philosophy within head and neck oncology is that further deintensifying
treatment could still provide equivalent oncologic outcomes, while further lowering toxicity
profiles and improving functional outcomes even more. There are now numerous trials
investigating deintensification in an attempt to minimize the morbidity incurred by patients,
and strategies have varied greatly. But still, there is no level I evidence for
deintensification, and certainly, no consensus on the best strategies for treatment moving
forward in the near future.
One such trial focusing on surgical therapy with de-escalated radiotherapy is ECOG-3311, a
randomized phase II trial which focuses on a primary surgical approach for cT1-2 N1-2b (as
per AJCC 7th edition) HPV+ OPSCC. The study de-escalates the adjuvant radiation dose to 50
gray for intermediate risk patients based on surgical pathology results. But even in this
study, nearly a third of the patients received adjuvant chemoradiation therapy which raises
concerns for even worse functional outcomes in those patients receiving triple modality
therapy (surgery, radiation, and chemotherapy). The final results of this study are still
pending.
In another phase II trial, the Mayo Clinic group randomized patients to either standard
adjuvant treatment or deintensified treatment after TORS, administering between 30 to 36 Gray
of radiation along with concurrent docetaxel infusion in the latter group. In that study, the
most important risk factors for progression were higher T stage, pN2 disease (5 or more
positive nodes), and the presence of ENE. Moreover, those with pN2 and ENE were at high risk
for distant failure. The 3-year progression-free survival (PFS) rate for the deintensified
cohort was 87%, compared to the standard cohort PFS of 90%. The group still concluded that
even patients with high risk features could still benefit from deintensification as both
groups did poorly from a distant disease standpoint.
Other studies have shown the significance of having pN2 disease, as well, with associated
higher risk for distant disease. In a large multi-institutional study, patients with HPV+
OPSCC who underwent primary surgical therapy and found to have 4 or fewer positive nodes had
improved 5-year overall survival compared to those with 5 or more positive nodes (89% vs 71%,
respectively). This was the basis for the change in staging for the AJCC 8th edition in which
pN1 was designated for 1 to 4 positive nodes and pN2 for 5 or more positive nodes. Moreover,
ENE was removed as a stratifying factor in the N staging for HPV+ OPSCC, as previously
mentioned. The significance of ENE remains a point of contention, and there is currently no
level I evidence for the optimal management of ENE in the adjuvant setting for surgically
managed HPV+ OPSCC. Often times, chemotherapy is recommended if ENE is identified, but the
addition of the third modality significantly worsens toxicity profile without assuredly
providing benefit. Recent NCCN guidelines recommend adjuvant radiation of 44 to 50 gray in
low risk, 54 to 63 gray in intermediate risk, and 60 to 66 gray for high risk patients, with
or without the addition of chemotherapy.
There is no doubt about the clinical impact of HPV+ OPSCC in the future of the national
healthcare system. Despite this, there is still no consensus on the best treatment strategies
for this disease. The investigators at IU have performed over 125 TORS operations in the last
four years since the inception of the Robotic Head and Neck Surgery Program with excellent
oncologic outcomes. The investigators anticipate the surgical volume to continue to grow as
the treatment paradigm shifts back to primary surgery and the incidence of HPV+ OPSCC
continues to rise. Thus, the purpose of this phase II prospective trial is to assess the
safety and efficacy of deintensification after surgical therapy in early stage HPV+ OPSCC by
evaluating oncologic outcomes, toxicity profiles, functional outcomes, and QOL measures, and
compare these factors to historical controls. This protocol also seeks to more clearly define
the setting and safety of eliminating of chemotherapy in the adjuvant setting after transoral
surgery for HPV+ OPSCC.
