Reduction of Hematologic Toxicity in Locally Advanced Cervical Cancers

Обзор

Cervical cancer is the fourth most common cancer among women and is mainly linked to infection with high-risk human papillomaviruses (HPV). Although most HPV infections resolve spontaneously, 570,000 women were diagnosed with cervical cancer in 2018, and more than half of them died from the disease. For locally advanced disease, concurrent chemoradiotherapy (RT-CT) followed by brachytherapy is considered the standard therapeutic treatment. Even though progress has been made in chemotherapy, external beam radiotherapy, and brachytherapy over the past decades-on the one hand by reducing the duration of chemotherapy-induced cytotoxicity, and on the other hand by decreasing radiation doses delivered to organs at risk-hematologic toxicity following concurrent chemoradiotherapy remains a frequent complication. The indication and benefit of chemotherapy have been demonstrated in phase III clinical trials; however, grade 3 hematologic toxicity (anemia, leukopenia, and thrombocytopenia) remains between 18.7% and 21.3%. Since total treatment duration is a prognostic factor for local control, brachytherapy must be administered near the end of or immediately after RT-CT so that total treatment time is as short as possible (≤ 50 days). If grade 3 hematologic toxicity persists after RT-CT (prior to brachytherapy), brachytherapy will be delayed, leading to a loss of disease control (Tanderup et al., 2016). Dose reduction to the bone marrow is possible, but to date no randomized trial has evaluated it. The objective of this multicenter French study is to assess whether bone-sparing-contouring of the pelvic and/or lumbosacral osseous structures as an organ at risk (OAR) during external radiotherapy planning-reduces the incidence of grade ≥ 3 hematologic toxicity and the use of leukocyte growth factors, platelet transfusions, and/or blood transfusions, while adhering to current recommendations and without compromising clinical outcomes in patients treated with RT-CT and brachytherapy for locally advanced cervical cancer.

Вмешательства

• Лучевая терапия radiotherapy with bone marrow contouring
  radiotherapy delivered while contouring the bone marrow to reduce hematologic toxicity

Первичные конечные точки

• Number of Participants With Grade ≥3 Hematologic Toxicity (CTCAE v5.0) [Срок оценки: At completion of concurrent chemoradiotherapy (Day 1 of brachytherapy planning visit).]

Вторичные конечные точки (9)

• Number of Participants With Grade ≥3 Hematologic Toxicity at Follow-up [Срок оценки: At 3 months and at 6 months after completion of concurrent chemoradiotherapy.]
• Mean Bone Marrow Dose (Gy) [Срок оценки: At radiotherapy treatment planning]
• Number of Participants Requiring Supportive Treatments [Срок оценки: From Day 1 of chemoradiotherapy initiation up to 90 days after chemoradiotherapy completion.]
• Overall treatment duration [Срок оценки: From date of first radiotherapy fraction until end of brachytherapy]
• Progression-free survival (PFS) [Срок оценки: From randomization up to 3 years of follow-up.]
• Local control [Срок оценки: From end of treatment through all follow-up visits (up to 3 years).]
• Incidence of bone fractures [Срок оценки: During the entire follow-up period (up to 3 years).]
• EORTC QLQ-C30 Global Health Score [Срок оценки: Baseline (Day 1), end of chemoradiotherapy (Week 5), and follow-up at 3, 6, 9, 12, 16, 20, 24, 30, 36 months.]
• Bone marrow metabolic activity [Срок оценки: Baseline (before chemoradiotherapy) and post-chemoradiotherapy (Day of brachytherapy planning CT).]

Критерии участия

Критерии включения

• Signed informed consent specific to the study.
• Age ≥ 18 years. Patients aged over 70 must be screened using the G-8 geriatric assessment tool; if required (G-8 score ≤ 14), an onco-geriatric consultation is mandatory to confirm eligibility.
• Histologically confirmed cervical cancer: squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma.
• Locally advanced cervical cancer according to the FIGO 2018 classification, confirmed by clinical staging and/or imaging.
• FIGO stage IB3 to IVA, for which definitive chemoradiotherapy with curative intent is planned.
• No evidence of metastatic disease outside the para-aortic region at initial staging (clinical exam, pelvic MRI, FDG-PET, and/or para-aortic lymph node staging by laparoscopy if applicable).
• Adequate hematologic and organ function, defined as laboratory results within 15 days prior to first study treatment:

Absolute neutrophil count (ANC) ≥ 1,500/mm³ without G-CSF support Total white blood cells > 2,000/mm³ Lymphocytes ≥ 500/mm³ Platelet count ≥ 100,000/mm³ without transfusion Hemoglobin ≥ 9.0 g/dL (transfusion allowed to meet this criterion)

• Patients eligible to receive cisplatin or carboplatin-based concurrent chemotherapy, with or without prior carbo-taxol neoadjuvant chemotherapy (as discussed in the protocol comments).
• Women of childbearing potential must have a negative pregnancy test (β-HCG) within 7 days before treatment and commit to highly effective contraception until 6 months after chemotherapy.

Критерии исключения

• Histologic types of cervical cancer other than those listed in the inclusion criteria.
• FIGO IB1, IB2, or IIA stages without regional lymph node metastasis (N0).
• FIGO IVB cervical cancer with distant metastases beyond para-aortic lymph nodes.
• Previous surgery for cervical cancer, except conization or para-aortic lymphadenectomy.
• Previous pelvic radiotherapy, other radiotherapy, or immunotherapy, except allowed neoadjuvant chemotherapy.
• Any malignancy other than the study disease within the past 5 years, except non-melanoma skin cancers (BCC, SCC).
• Pregnant or breastfeeding women, or women planning pregnancy during the study.
• For patients ≥70 with G-8 ≤14: non-confirmation of eligibility by the onco-geriatrician.
• Contraindication to cisplatin and/or carboplatin.
• Peripheral neuropathy ≥ grade 2.
• Systemic corticosteroids or systemic immunosuppressive drugs within 2 weeks before randomization (inhaled corticosteroids and mineralocorticoids such as fludrocortisone are allowed).
• Untreated osteoporosis (T-score ≤ -3) diagnosed on bone densitometry performed within 6 months prior to inclusion.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07461142 · RETHEMCOL-IPC 2023-019

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗