Clinical trial NCT06137833: Wide Spectrum Micronutrients Supplementation in Patients with Cancer Related Fatigue During Neoadjuvant and Adjuvant Chemotherapy
Official title: Clinical Study on Wide Spectrum Micronutrients Supplementation in Patients with Cancer Related Fatigue During Neoadjuvant and Adjuvant Chemotherapy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Fatigue
Breast Cancer
Lead sponsor: Pharmanutra S.p.a.
Sponsor class: INDUSTRY
Collaborators: name: Latis S.r.l.
First posted: 2023-11-18
Enrollment: 92
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: The goal of this clinical trial is to test the effect of the administration of APPORTAL® in addition to the SoC (recommended physical exercise), in patients with breast cancer, suffering from fatigue during neoadjuvant and adjuvant chemotherapy. The main questions it aims to answer are:

* if the food supplement APPORTAL® can be of help in supporting the physiological energy level, against the fatigue symptom in cancer patients undergoing adjuvant chemotherapy;
* if the supplementation with APPORTAL® can optimize the nutritional status, the muscular strength, the quality of life of the patient.

Also, the patients' satisfaction on the product received, the adherence to treatment will be evaluated and the overall safety and tolerability of the study product.

The patients will be asked to perform 3 study visits from baseline to the end of treatment (at 4 and 8 weeks after baseline) and a follow-up visit after 12 weeks from baseline.

The main assessments at each visit will be:

* physical examination, weight, Body Mass Index (BMI), body temperature (°C), heart rate, respiratory frequency, and systolic and diastolic blood pressure;
* previous and concomitant treatments;
* fatigue assessment through BFI questionnaire;
* quality of life through questionnaire SF-12;
* muscular strength (dynamometer)
* Adverse Event check (from Visit 2) Moreover, at visit 1 (baseline) and at visit 3 (end of treatment) a blood sample will be collected to evaluate the blood metabolites.

Telephonic follow-up will be done at 2 weeks, 6 weeks, 10 weeks to assess compliance and to recommendations on physical activity and to study treatment (only at 2 and 6 weeks) and tolerability/safety.

Participants will receive the nutrition supplement or the placebo, in addition to the SoC (recommended physical exercise), for 8 weeks.

Researchers will compare Apportal® and Placebo groups to see if the physiological energy level against the fatigue symptom, the nutritional status, the muscular strength, the quality of life of the patient improve after 8 weeks of treatment with APPORTAL® in addition to SoC (recommended physical exercise).

Detailed description: SAMPLE SIZE DETERMINATION Considering the average of the BFI 5 in the placebo group and the average 3 in the treated group, with standard deviation of 3, power at 80% and alpha 0.05, we obtain 37 patients per group, thus a total of 74 patients. If a drop-out rate of 20% is fixed, 92 patients in total are obtained. So, a sample of 92 subjects would be sufficient.

DATA SAFETY MONITORING BOARD / DATA MONITORING COMMITTEE No Data Safety Monitoring Board (DSMB) or Data Monitoring Committee (DMC) will be convened for the evaluation of safety data during the study. However, the Network Italiano Cure di Supporto in Oncologia (NICSO) society will be in charge of the evaluation of safety information. In fact, a Scientific Committee, composed by NICSO members, has been established to support the Sponsor in the continuous evaluation of safety data emerging from the study.

MONITORING AND QUALITY ASSURANCE The study will be monitored by adequately qualified and trained clinical monitors. Before the start of the study, the CRO (Contract Research Organization) responsible for the study site has the task to assess the adequacy of the study site and the staff involved. After start, the study will be monitored to ensure the proper conduct of the clinical study.

DATA COLLECTION An Electronic Case Report Form (e-CRF) will be used for recording patient's study data.

The Investigator will maintain a list of all persons authorized to make entries and/or corrections on the CRFs. Each authorized person will be provided with a user-specific ID (Identification) protected by a renewable password. Data entries and corrections will be made only by the authorized persons. The e-CRF system will record date and time of any entry and /or correction and the user ID of the person making the entry/correction. The system will keep track of all old and new values (audit trail).

Eligibility criteria: Inclusion Criteria:

1. Females aged 18 or higher.
2. Patients diagnosed with histologically confirmed breast cancer.
3. Patients having done at least one cycle of neoadjuvant or adjuvant chemotherapy (independently from type of chemotherapy) and who are on active chemotherapy treatment throughout the duration of the study (\*).
4. Patients with ECOG performance status ≤1 at screening.
5. Patients with cancer related fatigue of moderate-severe intensity (Numerical Rating Scale NRS \> 4).
6. Patients able to follow the recommendations on the physical exercise to do.
7. Patients who accept to use adequate contraceptive methods, if they are of child-bearing potential.
8. Patients willing and able to give signed informed consent and, in the opinion of the Investigator, to comply with the protocol tests and procedures.

(\*)Examples of chemotheraphy and standard therapeutic regimens in the neoadjuvant and adjuvant phase in breast cancer and on the basis of the biological characteristics of the neoplasm are as follows:

Neoadjuvant Chemotheraphy

* Epirubicin + Cyclophosphamide, 3 cycles -\> Taxol\* weekly for 12 weeks;
* Epirubicin + Cyclophosphamide -\> Pertuzumab + Trastuzumab (or Phesgo) 3 cycles + Taxol weekly for 12 weeks;
* Carboplatin + Taxol\* weekly for 12 weeks -\> Epirubicin + Cyclophosphamide;

  * Taxol could be replaced by Taxotere

Adjuvant Chemotheraphy

* Epirubicin + Cyclophosphamide, 4 cycles, every 21 days -\> Taxol weekly for 12 weeks
* Epirubicin + Cyclophosphamide, 4 cycles, every 14 days -\> Taxol, 4 cycles every 14 days
* Epirubicin + Cyclophosphamide, 4 cycles every 21 days -\> Taxol weekly + Trastuzumab with or without Pertuzumab for 1 year
* Taxotere + Cyclophosphamide, 4 cycles, every 21 days.

These lists are not to be considered exclusive

Exclusion Criteria:

1. Women who are pregnant or breast-feeding.
2. Neoplastic disease other than primary breast cancer.
3. Had major surgery other than breast cancer surgery (central venous access placement and tumor biopsies are not considered major surgery) within 4 weeks prior to randomization. Patients must be well recovered from acute effects of surgery prior to screening. Patients should not have plans to undergo major surgical procedures during the treatment period.
4. Patients with known or symptomatic metastases.
5. Patients unable to readily swallow. Patients with severe gastrointestinal disease (including esophagitis, gastritis, malabsorption, or obstructive symptoms) or intractable or frequent vomiting are excluded.
6. Patients with known or suspected allergy or hypersensitivity to the study products or any of their excipients.
7. Patients with an active, uncontrolled infection.
8. Patients with uncontrolled diabetes mellitus.
9. Patients with untreated clinically relevant hypothyroidism.
10. Patients with concomitant not-correctable alterations, present before chemotherapy, possible determinants of fatigue (NRS ≥ 4), such as anemia, not well controlled pain (NRS \> 4), insomnia, electrolyte imbalance, dehydration, anorexia/cachexia, hepatic, renal or heart failure, adrenocortical failure, neurological deficit.
11. Other clinical diagnosis, serious chronic diseases (renal failure with creatinine clearance \<30 ml / min; liver failure, heart failure with NYHA -New York Heart Association- class\> 2), ongoing or intercurrent illness that in the Investigator's opinion would prevent the patient's participation.
12. Patients receiving opioids or corticosteroids (except as replacement therapy at physiological dose, in subjects with adrenal insufficiency or to prevent emesis on the chemotherapy day).
13. Patients receiving parenteral nutrition (either total or partial).
14. Use of other investigational drug(s) within 30 days before study entry or during the study.
15. Triple negative patients in neoadjuvant treatment with Pembrolizumab.

Primary outcomes:
measure: The change of fatigue perception by the patient through the BFI questionnaire
timeFrame: Change from baseline to 8 weeks of treatment (Visit 3), in active and placebo groups.
Secondary outcomes:
measure: The change of fatigue perception by the patient through the BFI questionnaire
timeFrame: Change after 4, 8 and 12 weeks with respect to baseline in both the active and placebo groups
measure: Change in Iron status through hemoglobin assessment
timeFrame: Change after 8 weeks of study treatment with respect to baseline, in both the active and placebo groups
measure: Change in Iron status through ferritin assessment
timeFrame: Change after 8 weeks of study treatment with respect to baseline, in both the active and placebo groups
measure: Change in Iron status through transferrin saturation assessment
timeFrame: Change after 8 weeks of study treatment with respect to baseline in both the active and placebo groups
measure: Change in nutritional status through albumin assessment
timeFrame: Change after 8 weeks of study treatment with respect to baseline in both the active and placebo groups
measure: Change in nutritional status through assessment of total cholesterol, HDL, LDL and triglycerides
timeFrame: Change after 8 weeks of study treatment with respect to baseline in both the active and placebo groups
measure: Change in oxidative status through homocysteine assessment
timeFrame: Change after 8 weeks of study treatment with respect to baseline in both the active and placebo groups
measure: Change in oxidative status through uric acid assessment
timeFrame: Change after 8 weeks of study treatment with respect to baseline in both the active and placebo groups
measure: Change in oxidative status through C-Reactive Protein (CRP) assessment
timeFrame: Change after 8 weeks of study treatment with respect to baseline in CRP in both the active and placebo groups
measure: Change in serum L-arginina levels
timeFrame: Change after 8 weeks of study treatment with respect to baseline in both the active and placebo groups
measure: Changes in QoL through SF-12 Questionnaire
timeFrame: Change after 4, 8 and 12 weeks with respect to baseline in both the active and placebo groups
measure: Change in muscular strength (hand grip test),
timeFrame: Change after 4, 8 and 12 weeks with respect to baseline in both the active and placebo groups
measure: Overall patient's satisfaction with the product received, through a 5-points Likert scale
timeFrame: End of treatment (after 8 weeks of study treatment), in both the active and placebo groups
measure: Adherence to treatment
timeFrame: After 4 weeks and after 8 weeks from baseline
Other outcomes:
measure: Study product tolerability
timeFrame: Through study completion, an average of 12 weeks, in active and placebo groups
measure: Change in Physical Examination through weight measurement
timeFrame: Change after 4, 8 and 12 weeks from baseline in both the active and placebo groups
measure: Change in Physical Examination through BMI evaluation
timeFrame: Change after 4, 8 and 12 weeks from baseline in both the active and placebo groups
measure: Change in Physical Examinations through clinical evaluation by system
timeFrame: After 4, 8 and 12 weeks from baseline in both the active and placebo groups
measure: Change in vital signs through body temperature measurement
timeFrame: Change after 4, 8 and 12 weeks from baseline in Body temperature, in both the active and placebo groups
measure: Change in vital signs through Respiratory Frequency measurement
timeFrame: Change after 4, 8 and 12 weeks from baseline in Heart Rate, in both the active and placebo groups
measure: Change in vital signs through Heart Rate measurement
timeFrame: Change after 4, 8 and 12 weeks from baseline in both the active and placebo groups
measure: Change in vital signs through blood pressure measurement
timeFrame: Change after 4, 8 and 12 weeks from baseline in both the active and placebo groups
Locations:
city: Rozzano
country: Italy
facility: Cancer Center U.O. Oncologia Medica ed Ematologia IRCCS Humanitas Research Hospital
state: Milano
city: Brescia
country: Italy
facility: U.O.C. Oncologia medica ASST Spedali Civili di Brescia
city: Pisa
country: Italy
facility: U.O. Oncologia 2 Universitaria A.O.U. Pisana
city: Rome
country: Italy
facility: UOSD di Medicina di Precisione e Senologia, Policlinico Universitario A. Gemelli
city: Udine
country: Italy
facility: Dipartimento di Oncologia Azienda Sanitaria Universitaria Integrata di Udine
Study officials:
affiliation: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
name: Alessandra Fabi
role: PRINCIPAL_INVESTIGATOR
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