Phase I/II Trial Evaluating Carbon Ion Radiotherapy for the Treatment of Recurrent Rectal Cancer

Study Overview
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Brief Summary
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Treatment standard for patients with rectal cancer depends on the initial staging and includes surgical resection, radiotherapy as well as chemotherapy. For stage II and III tumors, radiochemotherapy should be performed in addition to surgery, preferentially as preoperative radiochemotherapy or as short-course hypofractionated radiation. Advances in surgical approaches, especially the establishment of the total mesorectal excision (TME) in combination with sophisticated radiation and chemotherapy have reduced local recurrence rates to only few percent. However, due to the high incidence of rectal cancer, still a high absolute number of patients present with recurrent rectal carcinomas, and effective treatment is therefore needed. Carbon ions offer physical and biological characteristics. Due to their inverted dose profile and the high local dose deposition within the Bragg peak precise dose application and sparing of normal tissue is possible. Moreover, in comparison to photons, carbon ions offer an increase relative biological effectiveness (RBE), which can be calculated between 2 and 5 depending on the cell line as well as the endpoint analyzed. Japanese data on the treatment of patients with recurrent rectal cancer previously not treated with radiation therapy have shown local control rates of carbon ion treatment superior to those of surgery. Therefore, this treatment concept should also be evaluated for recurrences after radiotherapy, when dose application using conventional photons is limited. Moreover, these patients are likely to benefit from the enhanced biological efficacy of carbon ions. In the current Phase I/II-PANDORA-01-Study the recommended dose of carbon ion radiotherapy for recurrent rectal cancer will be determined in the Phase I part, and feasibility and progression-free survival will be assessed in the Phase II part of the study. Within the Phase I part, increasing doses from 12 x 3 Gy E to 18 x 3 Gy E will be applied. The primary endpoint in the Phase I part is toxicity, the primary endpoint in the Phase II part its progression-free survival.

Official Title
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Phase I/II Trial Evaluating Carbon Ion Radiotherapy for the Treatment of Recurrent Rectal Cancer

Conditions
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Recurrent Rectal Cancer

Intervention / Treatment
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* Radiation: Carbon Ion Radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Locally recurrent rectal cancer Inoperable lesion Macroscopic tumor up to 1000ml volume- prior photon radiation of 20-60 Gy time between initial radiotherapy and re-irradiation of at least 12 months age ≥ 18 years of age Karnofsky Performance Score >60 For women with childbearing potential, (and men) adequate contraception. Ability of subject to understand character and individual consequences of the clinical trial Written informed consent (must be available before enrolment in the trial) Exclusion Criteria refusal of the patients to take part in the study advanced metastatic disease Patients who have not yet recovered from acute toxicities of prior therapies Known carcinoma < 5 years ago (excluding Carcinoma in situ of the cervix, basal cell carcinoma, squamous cell carcinoma of the skin) requiring immediate treatment interfering with study therapy- Pregnant or lactating women Participation in another clinical study or observation period of competing trials, respectively.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Carbon Ion Radiotherapy<br> | Radiation: Carbon Ion Radiotherapy<br>* Treatment with carbon ion radiotherapy using the rasterscanning technique<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Efficacy | Phase I part: The primary endpoint is toxicity measured by any Grade IV toxicity related to the study treatment according to CTCAE Grade 41. A maximum of 45 patients are projected for the Phase I part of the study. Patients will be followed for at least 3 months after study treatment to document any toxicity according to CTCAE Version 4.0. Phase II part: The primary endpoint is progression-free survival after re-irradiation at 12 months, therefore patients are followed within the trial protocol for a minimum 12 months after completion of study treatment. | 3 months |