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

• Conditions: Locally Advanced Malignant Neoplasm
• Interventions: Other: Hyperthermia

• Registration Number: NCT05099809
• Lead Sponsor: Mahatma Gandhi Institute of Medical Sciences

Brief Summary

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

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

1. Locoregional tumour control

2. Local disease free survival

3. Overall survival

ii. Evaluate the safety of hyperthermia along with standard therapeutic modalities of radiotherapy and/or chemotherapy

1. Acute morbidity

2. Late morbidity

iii. Evaluate the feasibility of carrying out hyperthermia by repurposing 27.12 MHz short wave diathermy unit that could be cost-effective

Study Timeline

• Study First Submitted: 2021-10-16
• Study First Submitted QC: 2021-10-21
• Study First Posted: 2021-10-29
• Study Start: 2021-12-01
• Status Verified: 2022-05
• Last Update Submitted: 2022-05-01
• Last Update Posted: 2022-05-05
• Primary Completion: 2022-12-31
• Study Completion: 2023-06-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

1. 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)
2. Following work up, patients should have no metastatic disease (M0)
3. Age > 18 years
4. Karnofsky performance status (KPS) ≥ 80
5. Written informed consent and agree to comply with the protocol
6. Adequate kidney and liver functions as assessed on biochemical investigations
7. Absence of psychological, familial, sociological or geographical condition that could potentially hamper compliance with the study protocol and follow-up schedule

Exclusion Criteria

1. Prior radiotherapy to the site of treatment
2. 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
3. Psychiatric or addictive disorders or other conditions that, in the opinion of the investigator would preclude the patient from meeting the study requirements.
4. Patients having metal implants, pacemakers or clustered markers.
5. Connective disease disorders that contraindicate radiotherapy, e.g., Scleroderma
6. Any known contraindication or hypersensitivity to the chemotherapeutic agents
7. Pregnancy, lactation period or lack of reliable contraception
8. 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
9. 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
10. Breast feeding female patients

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Hyperthermia	Hyperthermia	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: 1. Radiotherapy and Hyperthermia 2. Concurrent chemoradiotherapy and hyperthermia 3. 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 1. Locoregional disease control 2. Disease free survival 3. Overall Survival 4. Acute morbidity 5. Late morbidity

Primary Outcome Measures

Name	Time	Method
Locoregional tumour control	At 3 months after the completion of primary treatment	Locoregional control of the tumour
Disease free survival	Through study completion, an average of 1 year	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
Overall survival	Through study completion, an average of 1 year	From date of registration until the date of death from any cause, assessed till end of the study completion, an average of 1 year

Secondary Outcome Measures

Name	Time	Method
Acute treatment related morbidity	Till 3 months following the completion of primary treatment	Acute treatment morbidity as per CTCAE 5.0 guidelines
Late treatment related morbidity	Through study completion, an average of 1 year	Late treatment morbidity as per CTCAE 5.0 guidelines

Trial Locations

Locations (1)

Mahatma Gandhi Institute of Medical Sciences,; 🇮🇳 Sevagram, Maharashtra, India