- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03332069
Modulated Electro-Hyperthermia Plus Chemo-radiation for Locally Advanced Cervical Cancer Patients in South Africa (mEHT)
A Phase III Randomised Trial Investigating the Benefits of the Addition of Modulated Electro-hyperthermia to Chemo-radiation for Cervical Cancer in HIV Positive and Negative Women in South Africa
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Anticipated)
Phase
- Phase 3
Contacts and Locations
Study Contact
- Name: Carrie A Minnaar, PhD student
- Phone Number: +27721234292
- Email: cazzminn1@gmail.com
Study Contact Backup
- Name: Jeffrey A Kotzen, MBCHB
- Phone Number: +27825747985
- Email: jkotzen@yahoo.com
Study Locations
-
-
Gauteng
-
Johannesburg, Gauteng, South Africa, 2163
- Recruiting
- Charlotte Maxeke Johannesburg Academic Hospital
-
Contact:
- Jeffrey A Kotzen, MBBCH
- Phone Number: +27825747385
-
Contact:
- Carrie A Minnaar, Masters
- Phone Number: +27721234292
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Participants (who have been adequately clinically staged by standard clinical guidelines) with biopsy proven primary, untreated, histologically confirmed invasive squamous and aden-squamous cell carcinoma of the uterine cervix, FIGO (Fédération Internationale de Gynécologie et d'Obstétrique) stages advanced IIB (invasion of the distal half of the parametrium), IIIA and IIIB.
- HIV positive participants will be accepted.
The following laboratory tests will be done prior to enrolment in the study and the values must be in the following ranges:
- Haemoglobin >10 g/dL;
- Platelet count >150/mm3;
- Absolute neutrophil count (ANC) >3000/mm3
- Creatinine clearance>60 mL/min
- Liver function tests
- Females between the ages of 18 and 70 years.
- Ability to understand and the willingness to sign a written informed consent document.
- Eastern Cooperative Oncology Group (ECOG) score of not more than 2.
- Participants of childbearing potential must have a negative urine or serum pregnancy test prior to enrolment and use an effective form of contraception (e.g. barrier contraception, highly effective hormonal contraception).
- At the investigators' discretion, participants must be suitable for treatment with radical intent using concurrent chemotherapy and pelvic radiation. Subjects who undergo emergency RT in the form of brachytherapy for haemostasis, prior to enrolment will be allowed to be screened and enrolled provided they meet all other eligibility criteria.
- Life expectancy of greater than 12 months.
Participants must have a body mass index (BMI) that is within normal ranges.
-
Exclusion Criteria:
- Participants who have undergone hysterectomy.
- Exclude para-aortic lymph involvement on planning CT (without contrast)
- Patients with life-threatening AIDS defining illnesses (other than cervical carcinoma) will be excluded, as will patients with a CD4 count < 200/µL and not on ARVs.
- Patients with acute active (such as tuberculosis or malaria), serious, uncontrolled infections will be excluded.
- Participants will be excluded if there is evidence of resistance to antiretroviral therapy (i.e. HIV viral load > 400 copies/mL despite combination antiretroviral therapy for at least 4 months).
- Prior invasive malignancy other than cervical cancer, diagnosed within the past 24 months, excluding in situ anal dysplasia or carcinoma in situ, non-melanoma skin carcinoma, or Kaposi's sarcoma that has not required systemic chemotherapy within the past 24 months.
- Pregnant or breast-feeding women.
- A medical or psychiatric illness that prevents the participant from being able to sign an informed consent or would affect the participant's ability to comply with the protocol stipulations.
- Participants with circumstances that will not permit completion of the study or required follow-ups. For instance if travel to and from treatment site is an issue.
- Participants with carcinoma of the cervical stump.
Participants with a history of cardiovascular disease manifested as
- History of myocardial infarction
- Unstable angina
- Currently taking medication for treatment of angina
- History of coronary artery bypass surgery
Participants with contraindications to modulated electro-hyperthermia treatment:
- Pace makers and other implanted devices which rely on current and charges.
- Large metal implants, such as hip replacements.
- Inability to feel temperature in the region.
- Inability to express or vocalise discomfort or heat at the treatment site.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Study
50 Gy external beam radiation administered in fractions of 2 Gy 3 Doses of 8 Gy High Dose Rate brachytherapy up to 3 doses of 80mg/m2 of Cisplatin 10 modulated electro-hyperthermia treatments (55 minutes at a maximum of 150W)
|
Other Names:
Other Names:
Modulated electro-hyperthermia device used is the EHY 2000 by Oncotherm GmbH
Other Names:
High Dose Rate
Other Names:
|
Active Comparator: Control
50 Gy external beam radiation administered in fractions of 2 Gy 3 Doses of 8 Gy High Dose Rate brachytherapy up to 3 doses of 80mg/m2 of Cisplatin
|
Other Names:
Other Names:
High Dose Rate
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Local Disease Control
Time Frame: 6 months post treatment
|
Assessed by PET/CT using the RESIST/PERSIST criteria: complete response, complete metabolic response, partial response, stable disease, progressive disease.
|
6 months post treatment
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progression Free Survival
Time Frame: 24 months post treatment
|
To determine the progression-free survival (PFS) at 6, 12, 18 and 24 months after the last treatment date.
|
24 months post treatment
|
2 Year Survival
Time Frame: 24 months post treatment
|
Determine the overall survival at two years and the cause of death (i.e.
cancer-related, HIV-related, treatment related or other).
|
24 months post treatment
|
Incidence of Adverse Events Attributed to mEHT as assessed by CTCAE version 4.0
Time Frame: 6 months post treatment
|
To evaluate the adverse events that can be directly attributed to mEHT treatments.
|
6 months post treatment
|
Incidence of Treatment Related Adverse Events Attributed to Cisplatin as assessed by CTCAE version 4.0
Time Frame: Up to 3 months post treatment completion
|
The incidence of treatment-emergent adverse events which can be attributed to Cisplatin in each arm will be compared in order to identify any potential effect of mEHT on the frequency and severity of adverse events attributed to Cisplatin.
|
Up to 3 months post treatment completion
|
Number of participants with Early Treatment Related Adverse Events as assessed by CTCAE version 4.0
Time Frame: Up to 6 months post treatment completion
|
The incidence of early toxicity symptoms (graded using the CTCAE version 4 criteria) associated with radiotherapy in each arm of the study will be compared to identify any potential effect of the mEHT on the incidence and severity of early toxicity.
|
Up to 6 months post treatment completion
|
Number of participants with Late Treatment Related Adverse Events as assessed by CTCAE version 4.0
Time Frame: Up to 24 months post treatment completion
|
The incidence of late toxicity symptoms (graded using the CTCAE version 4 criteria) associated with radiotherapy in each arm of the study will be compared to identify any potential effect of the mEHT on the incidence of late toxicity in the sample group.
|
Up to 24 months post treatment completion
|
Visual Analogue Scale On the EuroQoL EQ-5D-5L form
Time Frame: Up to 24 months post treatment completion
|
To evaluate the changes from baseline value at set time points (6 weeks, 3 months, 6 months, 9 months, 12 months,18 months, 24 months) of the Visual Analogue Scale on the EuroQoL EQ-5D-5L form
|
Up to 24 months post treatment completion
|
Mobility On the EuroQoL EQ-5D-5L form
Time Frame: Up to 24 months post treatment completion
|
To evaluate the changes from baseline value at set time points (6 weeks, 3 months, 6 months, 9 months, 12 months,18 months, 24 months) of Mobility on the EuroQoL EQ-5D-5L form
|
Up to 24 months post treatment completion
|
Self-Care On the EuroQoL EQ-5D-5L form
Time Frame: Up to 24 months post treatment completion
|
To evaluate the changes from baseline value at set time points (6 weeks, 3 months, 6 months, 9 months, 12 months,18 months, 24 months) of Self-Care on the EuroQoL EQ-5D-5L form
|
Up to 24 months post treatment completion
|
Usual Activities On the EuroQoL EQ-5D-5L form
Time Frame: Up to 24 months post treatment completion
|
To evaluate the changes from baseline value at set time points (6 weeks, 3 months, 6 months, 9 months, 12 months,18 months, 24 months) of Usual Activities on the EuroQoL EQ-5D-5L form
|
Up to 24 months post treatment completion
|
Pain/Discomfort On the EuroQoL EQ-5D-5L form
Time Frame: Up to 24 months post treatment completion
|
To evaluate the changes from baseline value at set time points (6 weeks, 3 months, 6 months, 9 months, 12 months,18 months, 24 months) of Pain/Discomfort on the EuroQoL EQ-5D-5L form
|
Up to 24 months post treatment completion
|
Anxiety/Depression On the EuroQoL EQ-5D-5L form
Time Frame: Up to 24 months post treatment completion
|
To evaluate the changes from baseline value at set time points (6 weeks, 3 months, 6 months, 9 months, 12 months,18 months, 24 months) of Anxiety/Depression on the EuroQoL EQ-5D-5L form
|
Up to 24 months post treatment completion
|
Score on the EORTC-QLQ 30 for Global Health Status
Time Frame: Up to 24 months post treatment completion
|
To evaluate the changes from baseline scores at set time points (6 weeks, 3 months, 6 months, 9 months, 12 months,18 months, 24 months) of the Score on the EORTC-QLQ 30 for Global Health Status
|
Up to 24 months post treatment completion
|
Score on the EORTC-QLQ 30 for Physical Functioning
Time Frame: Up to 24 months post treatment completion
|
To evaluate the changes from baseline scores at set time points (6 weeks, 3 months, 6 months, 9 months, 12 months,18 months, 24 months) of the Score on the EORTC-QLQ 30 for Physical Functioning
|
Up to 24 months post treatment completion
|
Score on the EORTC-QLQ 30 for Role Functioning
Time Frame: Up to 24 months post treatment completion
|
To evaluate the changes from baseline scores at set time points (6 weeks, 3 months, 6 months, 9 months, 12 months,18 months, 24 months) of the Score on the EORTC-QLQ 30 for Role Functioning
|
Up to 24 months post treatment completion
|
Score on the EORTC-QLQ 30 for Emotional Functioning
Time Frame: Up to 24 months post treatment completion
|
To evaluate the changes from baseline scores at set time points (6 weeks, 3 months, 6 months, 9 months, 12 months,18 months, 24 months) of the Score on the EORTC-QLQ 30 for Emotional Functioning
|
Up to 24 months post treatment completion
|
Score on the EORTC-QLQ 30 for Cognitive Functioning
Time Frame: Up to 24 months post treatment completion
|
To evaluate the changes from baseline scores at set time points (6 weeks, 3 months, 6 months, 9 months, 12 months,18 months, 24 months) of the Score on the EORTC-QLQ 30 for Cognitive Functioning
|
Up to 24 months post treatment completion
|
Score on the EORTC-QLQ 30 for Social Functioning
Time Frame: Up to 24 months post treatment completion
|
To evaluate the changes from baseline scores at set time points (6 weeks, 3 months, 6 months, 9 months, 12 months,18 months, 24 months) of the Score on the EORTC-QLQ 30 for Social Functioning
|
Up to 24 months post treatment completion
|
Score on the EORTC-QLQ 30 for Fatigue
Time Frame: Up to 24 months post treatment completion
|
To evaluate the changes from baseline scores at set time points (6 weeks, 3 months, 6 months, 9 months, 12 months,18 months, 24 months) of the Score on the EORTC-QLQ 30 for Fatigue
|
Up to 24 months post treatment completion
|
Score on the EORTC-QLQ 30 for Nausea and Vomiting
Time Frame: Up to 24 months post treatment completion
|
To evaluate the changes from baseline scores at set time points (6 weeks, 3 months, 6 months, 9 months, 12 months,18 months, 24 months) of the Score on the EORTC-QLQ 30 for Nausea and Vomiting
|
Up to 24 months post treatment completion
|
Score on the EORTC-QLQ 30 for Pain
Time Frame: Up to 24 months post treatment completion
|
To evaluate the changes from baseline scores at set time points (6 weeks, 3 months, 6 months, 9 months, 12 months,18 months, 24 months) of the Score on the EORTC-QLQ 30 for Pain
|
Up to 24 months post treatment completion
|
Score on the EORTC-QLQ 30 for Dyspnoea
Time Frame: Up to 24 months post treatment completion
|
To evaluate the changes from baseline scores at set time points (6 weeks, 3 months, 6 months, 9 months, 12 months,18 months, 24 months) of the Score on the EORTC-QLQ 30 for Dyspnoea
|
Up to 24 months post treatment completion
|
Score on the EORTC-QLQ 30 for Insomnia
Time Frame: Up to 24 months post treatment completion
|
To evaluate the changes from baseline scores at set time points (6 weeks, 3 months, 6 months, 9 months, 12 months,18 months, 24 months) of the Score on the EORTC-QLQ 30 for Insomnia
|
Up to 24 months post treatment completion
|
Score on the EORTC-QLQ 30 for Appetite Loss
Time Frame: Up to 24 months post treatment completion
|
To evaluate the changes from baseline scores at set time points (6 weeks, 3 months, 6 months, 9 months, 12 months,18 months, 24 months) of the Score on the EORTC-QLQ 30 for Appetite Loss
|
Up to 24 months post treatment completion
|
Score on the EORTC-QLQ 30 for Constipation
Time Frame: Up to 24 months post treatment completion
|
To evaluate the changes from baseline scores at set time points (6 weeks, 3 months, 6 months, 9 months, 12 months,18 months, 24 months) of the Score on the EORTC-QLQ 30 for Constipation
|
Up to 24 months post treatment completion
|
Score on the EORTC-QLQ 30 for Diarrhoea
Time Frame: Up to 24 months post treatment completion
|
To evaluate the changes from baseline scores at set time points (6 weeks, 3 months, 6 months, 9 months, 12 months,18 months, 24 months) of the Score on the EORTC-QLQ 30 for Diarrhoea
|
Up to 24 months post treatment completion
|
Score on the EORTC-QLQ 30 for Financial Difficulties
Time Frame: Up to 24 months post treatment completion
|
To evaluate the changes from baseline scores at set time points (6 weeks, 3 months, 6 months, 9 months, 12 months,18 months, 24 months) of the Score on the EORTC-QLQ 30 for Financial Difficulties
|
Up to 24 months post treatment completion
|
Score on the EORTC-QLQ 24 for Symptom Experiences
Time Frame: Up to 24 months post treatment completion
|
To evaluate the changes from baseline scores at set time points (6 weeks, 3 months, 6 months, 9 months, 12 months,18 months, 24 months) of the Score on the EORTC-QLQ 30 for Symptom Experiences
|
Up to 24 months post treatment completion
|
Collaborators and Investigators
Sponsor
Investigators
- Study Chair: Carrie A Minnaar, Msc, Student - PhD Candidate
- Principal Investigator: Jeffrey A Kotzen, MBBCH, Senior Radiation Oncologist
- Study Chair: Ans Baeyes, PhD, Head of Department of Radiobiology
Publications and helpful links
General Publications
- Fiorentini G, Szasz A. Hyperthermia today: electric energy, a new opportunity in cancer treatment. J Cancer Res Ther. 2006 Apr-Jun;2(2):41-6. doi: 10.4103/0973-1482.25848.
- van der Zee J, Gonzalez GD. The Dutch Deep Hyperthermia Trial: results in cervical cancer. Int J Hyperthermia. 2002 Jan-Feb;18(1):1-12. doi: 10.1080/02656730110091919. Erratum In: Int J Hyperthermia. 2003 Mar-Apr;19(2):213.
- Minnaar CA, Kotzen JA, Naidoo T, Tunmer M, Sharma V, Vangu MD, Baeyens A. Analysis of the effects of mEHT on the treatment-related toxicity and quality of life of HIV-positive cervical cancer patients. Int J Hyperthermia. 2020;37(1):263-272. doi: 10.1080/02656736.2020.1737253.
- Minnaar CA, Kotzen JA, Ayeni OA, Naidoo T, Tunmer M, Sharma V, Vangu MD, Baeyens A. The effect of modulated electro-hyperthermia on local disease control in HIV-positive and -negative cervical cancer women in South Africa: Early results from a phase III randomised controlled trial. PLoS One. 2019 Jun 19;14(6):e0217894. doi: 10.1371/journal.pone.0217894. eCollection 2019.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- LACC-OT
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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