Registry Trial to Evaluate the Safety and Efficacy of Hyperthermia in Locally Advanced Cancers

Study Overview
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Brief Summary
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Mahatma Gandhi Institute of Medical Sciences (MGIMS), Sevagram, District Wardha, Maharashtra, India is located in a rural setup and caters to a very underprivileged patient population with limited resources to even pay for their treatment. As per the latest Indian Cancer Registry Report 2020, of the 28 population based cancer registries (PBCR), the age adjusted incidence rates (AAR) in males and females are 64.9 and 69.9. This makes the AAR in Wardha District (district where MGIMS is located) as one of the lowest ranked AAR both for male (national range: 39.5 - 269.4) and females (national range: 49.4 - 219.8) in the country. However, the %mortality / incidence, is one of the highest for Wardha, both for males (65.9%, national range: 14.7% - 71.9%) and females (53%, national range: 9% - 63%). This indicates that the prognosis of patients in this district is one of the worst in India and thus requires a new approach to their standard therapeutic option. This has to be cost-effective, without any significant additional morbidity, and should used in conjunction to the standard treatment of radiotherapy and/or chemotherapy. Hyperthermia, which is raising the tumor temperature to 40 - 43°C is perhaps one of the oldest forms of treatment for cancer. Hyperthermia, being a potent radiosensitizer, a chemosensitizer, an immunomodulator with no significantly added side effects, could be an effective therapeutic modality that could be expected to improve the outcome in these patients. However, it also needs to be cost-effective and require low capital cost investment so that other centers, especially in low and low-middle income countries could also introduce hyperthermia to the therapeutic armamentarium for cancer. This is a registry trial for patients being treated with hyperthermia along with radiotherapy and/or chemotherapy as per the standard departmental protocol for various locally advanced cancers.

Detailed Description
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To carry out a registry trial to evaluate the safety and efficacy of hyperthermia delivered by a repurposed short wave diathermy unit working at 27.1 MHz along with radiotherapy and/or chemotherapy in patients with locally advanced tumours of head neck cancers, cancer cervix, breast, oesophagus and anorectum attending the department of radiotherapy, MGIMS. This would help to create an organized system that uses observational methods to collect uniform data on safety and efficacy of hyperthermia when used in conjunction with standard therapeutic modalities of radiotherapy and/or chemotherapy. The study would help to, i. Evaluate the specific outcomes with hyperthermia in terms of the following clinical endpoints with hyperthermia Locoregional tumour control Local disease free survival Overall survival ii. Evaluate the safety of hyperthermia along with standard therapeutic modalities of radiotherapy and/or chemotherapy Acute morbidity Late morbidity iii. Evaluate the feasibility of carrying out hyperthermia by repurposing 27.12 MHz short wave diathermy unit that could be cost-effective

Official Title
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Registry Trial to Evaluate the Safety and Efficacy of Hyperthermia With Radiotherapy and/or Chemotherapy in Locally Advanced Cancers at MGIMS

Conditions
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Locally Advanced Malignant Neoplasm

Intervention / Treatment
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* Other: Hyperthermia


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histopathologically proven cases of locally advanced head and neck cancers (LAHNC), TNM stages III and IV and locally advanced cancer cervix (LACC), FIGO stages IIB - IVA, locally advanced (primarily inoperable T3 and T4 stages) and recurrent breast cancers, cancer oesophagus (TNM stages IIA and IVA), anorectal cancers (TNM stages IIA to IIIC) Following work up, patients should have no metastatic disease (M0) Age > 18 years Karnofsky performance status (KPS) ≥ 80 Written informed consent and agree to comply with the protocol Adequate kidney and liver functions as assessed on biochemical investigations Absence of psychological, familial, sociological or geographical condition that could potentially hamper compliance with the study protocol and follow-up schedule Exclusion Criteria: Prior radiotherapy to the site of treatment No prior or concurrent malignancies other than surgically treated squamous cell or basal cell carcinoma of the skin which are not in the area of the present malignancy Psychiatric or addictive disorders or other conditions that, in the opinion of the investigator would preclude the patient from meeting the study requirements. Patients having metal implants, pacemakers or clustered markers. Connective disease disorders that contraindicate radiotherapy, e.g., Scleroderma Any known contraindication or hypersensitivity to the chemotherapeutic agents Pregnancy, lactation period or lack of reliable contraception Any other disease or therapy, which, according to the investigator, present a risk to the patient or which are not compatible with the aims of the clinical trial Indications that the person concerned will possibly not keep to the clinical trial plan because of unwillingness to cooperate or difficulties in keeping the check-up appointments Breast feeding female patients

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Hyperthermia<br>Patients with locally advanced cancers reporting to Department of Radiotherapy at MGIMS who fulfil the eligibility criteria would be included in the study. Depending on the ongoing departmental protocols for various tumors the patients could be treated with either: Radiotherapy and Hyperthermia Concurrent chemoradiotherapy and hyperthermia Neoadjuvant chemotherapy and hyperthermia followed by surgery and/or radiotherapy Hyperthermia would be delivered using a shortwave diathermy unit operating at 27.1 MHz. Tumour response would be evaluated using RECIST criteria 1.1 while the acute and late morbidities would be scored as per CTCAE v5.0 guidelines. Outcome measures for each site would be undertaken and evaluated in terms of Locoregional disease control Disease free survival Overall Survival Acute morbidity Late morbidity | Other: Hyperthermia<br>* Hyperthermia would be delivered once/twice a week for 60 to 90 minutes depending on patient's tolerance. A shortwave diathermy unit operating at 27.1 MHz would be used to deliver locoregional hyperthermia.<br>* Other names: Surgery;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Locoregional tumour control | Locoregional control of the tumour | At 3 months after the completion of primary treatment | 
| Disease free survival | From date of registration until the date of first documented progression or date of death from any cause, whichever came first, assessed till end of the study completion, an average of 1 year | Through study completion, an average of 1 year | 
| Overall survival | From date of registration until the date of death from any cause, assessed till end of the study completion, an average of 1 year | Through study completion, an average of 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute treatment related morbidity | Acute treatment morbidity as per CTCAE 5.0 guidelines | Till 3 months following the completion of primary treatment | 
| Late treatment related morbidity | Late treatment morbidity as per CTCAE 5.0 guidelines | Through study completion, an average of 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hyperthermia, Radiotherapy, Chemotherapy, Registry trial, Short wave diathermy