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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Locally Advanced Malignant Neoplasm
• Intervention / Treatment: Other: Hyperthermia

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 Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

• Study Contact: Name: Niloy R Datta, MD, DNB, CCST; Phone Number: +91-9717388117; Email: niloydatta@mgims.ac.in
• Study Contact Backup: Name: Bharati M Jain, PhD; Phone Number: +91-9921590897; Email: bharati@mgims.ac.in

Study Locations

• India
  • Maharashtra
    • Sevagram, Maharashtra, India, 442101
      • Recruiting
      • Mahatma Gandhi Institute of Medical Sciences
      • Contact: Niloy R Datta, MD, DNB, CCST; Phone Number: +91-9717388117; Email: niloydatta@mgims.ac.in
      • Contact: Bharati M Jain, PhD; Phone Number: +91-9921590897; Email: bharati@mgims.ac.in
    • Sevagram, Maharashtra, India, 442102
      • Recruiting
      • Mahatma Gandhi Institute of Medical Sciences,
      • Contact: Niloy R Datta, MD, DNB; Phone Number: +919717388117; Email: niloydatta@magims.ac.in
      • Contact: Bharati M Jain, PhD; Phone Number: +919921590897; Email: bharati@mgims.ac.in

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

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)

Description

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 Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

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: 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; 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.; Other Names: Radiotherapy; Surgery; Chemotherapy

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Mahatma Gandhi Institute of Medical Sciences

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2021
• Primary Completion (Anticipated): December 31, 2022
• Study Completion (Anticipated): June 30, 2023

Study Registration Dates

• First Submitted: October 16, 2021
• First Submitted That Met QC Criteria: October 21, 2021
• First Posted (Actual): October 29, 2021

Study Record Updates

• Last Update Posted (Actual): May 5, 2022
• Last Update Submitted That Met QC Criteria: May 1, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Radiotherapy; Chemotherapy; Hyperthermia; Registry trial; Short wave diathermy
• Additional Relevant MeSH Terms: Wounds and Injuries; Body Temperature Changes; Heat Stress Disorders; Neoplasms; Hyperthermia; Fever
• Other Study ID Numbers: MahatmaIGMS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Share with all co-investigators
• IPD Sharing Time Frame: 24 months
• IPD Sharing Access Criteria: Limited only to coinvestigators till the completion of study.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No