Fasting on Newly Diagnosed Breast Cancer (STEFNE)

A Pilot Study of Short-term Fasting on Neoadjuvant Chemotherapy in Patients With Newly Diagnosed Breast Cancer (STEFNE Study)

This study is to see how safe the use of short-term fasting is in breast cancer patients who will receive chemotherapy before undergoing surgery and to examine if the use of short-term fasting will decrease the side effects of chemotherapy and how much a tumor shrinks while receiving chemotherapy.

Study Overview

• Status: Terminated
• Conditions: HER2-positive Breast Cancer
• Intervention / Treatment: Drug: Doxorubicin; Drug: cyclophosphamide; Drug: paclitaxel; Drug: docetaxel; Drug: Trastuzumab; Drug: Pertuzumab

Detailed Description

Patients will fast 24 hours before and 24 hours after the administration of chemotherapy which will consist of doxorubicin plus cyclophosphamide every 2 weeks for four cycles followed by paclitaxel every 2 weeks for four cycles (dose-dense AC + T) or docetaxel (T) every 3 weeks for four cycles. Trastuzumab (H) and Pertuzumab (P) will be given concurrently with docetaxel for a total of 4 cycles before surgery. For patients who do not achieve pathological complete remission (pCR), adjuvant chemotherapy with doxorubicin (A) plus cyclophosphamide (C) every 3 weeks for four cycles will be given, followed by trastuzumab every 3 weeks to complete 1 year of treatment. For patients with pCR, only trastuzumab every 3 weeks will be given adjuvantly to complete 1 year of treatment (TPH + AC).

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Goodyear, Arizona, United States, 85338
      • Western Regional Medical Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients ≥ 18 years of age with histologically, and radiographically confirmed non-metastatic breast cancer with minimal tumor size over 1 cm (≥T1c lesion) to receive neoadjuvant chemotherapy recommended by the treating physician
• For estrogen receptor (ER) strongly positive, human epithelial receptor (HER2) negative breast cancer, Oncotype Dx study is required. Patients with low recurrence score will be excluded in the study.
• Eastern Cooperative Oncology Group (ECOG) performance status score < 1
• Absolute neutrophil count > 1500 mm3, platelet count ≥ 100×109 L, hemoglobin ≥ 8.5 g/dL
• Serum creatinine ≤1.5 times the upper limit of the normal range, total bilirubin ≤ 1.5 X ULN (≤ 3 mg/dL if clinically diagnosed with Gilbert syndrome) AST/ALT ≤ 2.5 X ULN (AST/ALT ≤ 5X ULN if clinically diagnosed with Gilbert syndrome)
• Willing to provide blood samples for correlative research purposes
• Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically sterile) must be willing to use an acceptable contraceptive method (abstinence, oral contraceptive or double barrier method) for the duration of the study and for 30 days following the last dose of study drug, and must have a negative urine or serum pregnancy test within 2 weeks prior to beginning treatment on this trial.

Exclusion Criteria:

1. Uncontrolled cardiac disease, such as angina, hypertension or significant arrhythmias, congestive heart failure (NYHA grade 2 or more or LVEF < 40% on any prior assessment). Note: Assessment of LVEF is done before and after anthracycline-based or trastuzumab-based chemotherapy as standard of care
2. Pregnant or lactating females
3. Known history of diabetes mellitus. If screening fasting glucose is ≥126 mg/dL, an HbA1C must be < 6.5%.
4. History of syncope with calorie restriction in the past
5. Body mass index (BMI) < 19 kg/m2
6. Clinical signs or symptoms of GI obstruction and/or requirement for parenteral hydration or nutrition
7. Inability to complete informed consent process and adhere to the protocol treatment plan and follow-up requirements
8. Concurrent severe illness such as active infection, or psychiatric illness/social situations that would limit safety and compliance with study requirements
9. Any other medical comorbidity that requires daily medication(s) that may not be safely taken without food.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: HER2 negative breast cancer; Doxorubicin and cyclophosphamide every two weeks for four cycles (one cycle is defined as 14 days). After completing fourth cycle, paclitaxel every two weeks for an additional four cycles. The appropriate surgery will be done three to six weeks after completing the last cycle of paclitaxel.	Drug: Doxorubicin; doxorubicin (A) 60 mg/m2 plus cyclophosphamide (C) 600 mg/m2 every 2 weeks for four cycles followed by paclitaxel (T) 75 mg/m2 every 2 weeks for four cycles (dose-dense AC + T).20; Other Names: (dose-dense AC + T).2; Drug: cyclophosphamide; doxorubicin (A) 60 mg/m2 plus cyclophosphamide (C) 600 mg/m2 every 2 weeks for four cycles followed by paclitaxel (T) 75 mg/m2 every 2 weeks for four cycles (dose-dense AC + T).20; Other Names: (dose-dense AC + T).20; Drug: paclitaxel; For patients with HER2 negative breast cancer: doxorubicin (A) 60 mg/m2 plus cyclophosphamide (C) 600 mg/m2 every 2 weeks for four cycles followed by paclitaxel (T) 75 mg/m2 every 2 weeks for four cycles (dose-dense AC + T).20; Other Names: (dose-dense AC + T).20
Active Comparator: HER2 positive breast cancer; Docetaxel, trastuzumab, and pertuzumab every three weeks for four cycles. Pegfilgrastim after docetaxel. Surgery three to six weeks after completing the last docatexel. If additional chemotherapy is needed patients will receive both doxorubicin and cyclophosphamide every three weeks for four cycles and after the fourth cycle then trastuzumab for one year	Drug: docetaxel; For patients with HER2 positive breast cancer: docetaxel (T) 75 mg/m2 every 3 weeks for four cycles. Trastuzumab (H, 8mg/kg for 1st cycle, then 6 mg/kg in subsequent 3 cycles), Pertuzumab (P, 840 mg for 1st cycle, then 420 mg in subsequent 3 cycles) will be given concurrently with docetaxel for a total of 4 cycles before surgery. For patients who do not achieve pCR, adjuvant chemotherapy with doxorubicin (A) 60 mg/m2 plus cyclophosphamide (C) 600 mg/m2 every 3 weeks for four cycles will be given, followed by trastuzumab 6 mg/kg every 3 weeks to complete 1 year of treatment. For patients with pCR, only trastuzumab 6 mg/kg every 3 weeks will be given adjuvantly to complete 1 year of treatment (TPH + AC).21; Other Names: (TPH + AC).21; Drug: Trastuzumab; docetaxel (T) 75 mg/m2 every 3 weeks for four cycles. Trastuzumab (H, 8mg/kg for 1st cycle, then 6 mg/kg in subsequent 3 cycles), Pertuzumab (P, 840 mg for 1st cycle, then 420 mg in subsequent 3 cycles) will be given concurrently with docetaxel for a total of 4 cycles before surgery. For patients who do not achieve pCR, adjuvant chemotherapy with doxorubicin (A) 60 mg/m2 plus cyclophosphamide (C) 600 mg/m2 every 3 weeks for four cycles will be given, followed by trastuzumab 6 mg/kg every 3 weeks to complete 1 year of treatment. For patients with pCR, only trastuzumab 6 mg/kg every 3 weeks will be given adjuvantly to complete 1 year of treatment (TPH + AC).21; Other Names: (TPH + AC).21; Drug: Pertuzumab; docetaxel (T) 75 mg/m2 every 3 weeks for four cycles. Trastuzumab (H, 8mg/kg for 1st cycle, then 6 mg/kg in subsequent 3 cycles), Pertuzumab (P, 840 mg for 1st cycle, then 420 mg in subsequent 3 cycles) will be given concurrently with docetaxel for a total of 4 cycles before surgery. For patients who do not achieve pCR, adjuvant chemotherapy with doxorubicin (A) 60 mg/m2 plus cyclophosphamide (C) 600 mg/m2 every 3 weeks for four cycles will be given, followed by trastuzumab 6 mg/kg every 3 weeks to complete 1 year of treatment. For patients with pCR, only trastuzumab 6 mg/kg every 3 weeks will be given adjuvantly to complete 1 year of treatment (TPH + AC).21; Other Names: (TPH + AC).21

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological Response Rate at the Time of Surgery or at the Time of Biopsy	Evaluate pathological complete remission rate at the time of surgery, or partial pathological response rate (defined as residual invasive disease of 1cm) at the time of surgery or at the time of biopsy upon completion of planned chemotherapy.	4-6 cycles (up to 12 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fasting on the Toxicity of Neoadjuvant Chemotherapyaccording to the NCI	The effect of short-term fasting on the toxicity of neoadjuvant chemotherapy in breast cancer patients according to the NCI common toxicity criteria (Version 4.03)	4-6 cycles (up to 12 weeks)
Pathological Response Rate at the Time of Surgery or Time of Biopsy Upon Completion of Planned Chemotherapy	To evaluate pathological complete remission rate (defined as disappearance of all invasive tumor in the breast; ypT0-is) at the time of surgery, or partial pathological response rate (defined as residual invasive disease of 1cm, ypT1a-b) at the time of surgery or at the time of biopsy upon completion of planned chemotherapy for triple-negative breast cancer.	4-6 cycles
Insulin Abnormalities	Changes in plasma insulin abnormalities after short-term fasting and chemotherapy	4-6 cycles (up to 12 weeks)
Biomarker Changes Before and After Chemotherapy	Biomarker changes in breast cancer (biopsy or residual tumor) before and after neoadjuvant chemotherapy	4-6 cycles (up to 12 weeks)
Nutritional Assessment Before and After Neoadjuvant Chemotherapy	Nutritional status assessment with Patient Generated Subjective Global Assessment (aPG-SGA) before and after neoadjuvant chemotherapy	4-6 cycles (up to 12 weeks)
Glucose After Fasting and Chemotherapy	To investigate changes in glucose after short-term fasting and chemotherapy	4-6 cycles (up to 12 weeks)
Changes in Insulin-like Growth Factor-1	To investigate changes in Insulin-like growth factor-1 (IGF1) after short-term fasting and chemotherapy	4-6 cycles (up to 12 weeks)
Plasma Blood-based Tumor-related Abnormalities in DNA	To investigate changes in plasma blood-based tumor-related abnormalities in DNA after short-term fasting and chemotherapy	4-6 cycles (up to 12 weeks)

Collaborators and Investigators

• Sponsor: Western Regional Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2013
• Primary Completion (Actual): August 1, 2015
• Study Completion (Actual): August 1, 2015

Study Registration Dates

• First Submitted: January 12, 2015
• First Submitted That Met QC Criteria: March 4, 2015
• First Posted (Estimate): March 5, 2015

Study Record Updates

• Last Update Posted (Actual): April 24, 2018
• Last Update Submitted That Met QC Criteria: March 26, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Antibiotics, Antineoplastic; Docetaxel; Cyclophosphamide; Paclitaxel; Trastuzumab; Doxorubicin; Pertuzumab
• Other Study ID Numbers: 1145332

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No