Anatomic Stage III Breast Cancer AJCC v8 Clinical Trial
Official title:
Phase I/II Safety and Efficacy Study of Autophagy Inhibition With Hydroxychloroquine to Augment the Antiproliferative and Biological Effects of Pre-Operative Palbociclib Plus Letrozole for Estrogen Receptor-Positive and HER2-Negative Breast Cancer
Verified date | April 2024 |
Source | M.D. Anderson Cancer Center |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
This phase I/II trial studies the side effects and best dose of hydroxychloroquine when given together with palbociclib and letrozole before surgery in treating patients with estrogen receptor positive, HER2 negative breast cancer. Hydroxychloroquine is a substance that decreases immune responses in the body. Palbociclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Estrogen can cause the growth of breast cancer cells. Drugs, such as letrozole, may lessen the amount of estrogen made by the body. Giving hydroxychloroquine, palbociclib, and letrozole before surgery may work better than palbociclib and letrozole in treating patients with breast cancer.
Status | Completed |
Enrollment | 15 |
Est. completion date | April 17, 2024 |
Est. primary completion date | April 17, 2024 |
Accepts healthy volunteers | No |
Gender | Female |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: - Signed written informed consent - Diagnosis of estrogen positive breast cancer, estrogen receptor-positive and HER2-negative by American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) criteria - Eastern Cooperative Oncology Group (ECOG) performance status 0-1 - Postmenopausal defined by: a. Age >= 55 years and 1 year or more of amenorrhea b. Age < 55 years and 1 year or more of amenorrhea with luteinizing hormone (LH) and/or follicle stimulating hormone (FSH) levels in the postmenopausal range c. Age < 55 with prior hysterectomy but intact ovaries with LH and/or FSH levels in the postmenopausal range d. Chemotherapy or medically induced ovarian suppression with 1 year or more of amenorrhea and with LH and/or FSH levels in the postmenopausal range e. Status after bilateral oophorectomy (>= 28 days prior to first study treatment) - Absolute neutrophil count (ANC) >= 1500 cells/ul - Platelet count >= 100,000/ul - Serum creatinine concentration < 1.5 x upper limit of normal (ULN) - Bilirubin level < 1.5 x ULN - Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 3 x ULN - Alkaline phosphatase =< 2.5 ULN - Metastatic cohorts (Phase I): Diagnosis of stage IV estrogen positive breast cancer, estrogen receptor-positive and HER2-negative by ASCO/CAP criteria - Metastatic cohorts (Phase I): Must be a candidate for treatment with CDK4/6 inhibitor and hormonal therapy with an aromatase inhibitor as standard of care - Metastatic cohorts (Phase I): No prior exposure to CDK 4/6 inhibitors - Neoadjuvant cohorts (Phase II): Diagnosis of stage I-III estrogen positive breast cancer, estrogen receptor-positive and HER2-negative by ASCO/CAP criteria. If stage I, clinical tumor size must be >= 1.5 cm - Neoadjuvant cohorts (Phase II): Baseline tumor Ki67 > 5% - Neoadjuvant cohorts (Phase II): Surgical candidate and appropriate for pre-operative endocrine therapy Exclusion Criteria: - Prior exposure to CDK 4/6 inhibitor therapy - History of retinal disease or active visual disturbances (normal baseline study-specified retinal exam required) - Acute illness, including infections requiring medical therapy, known bleeding diathesis or need for anticoagulation - Treatment with any of the following medications within 4 weeks before the baseline diagnostic biopsy is taken: a. Oral estrogens, including hormone replacement therapy (but prior depot estrogen use not allowed). b. Investigational agents (or 5 half-lives, whichever is longer) - Required concomitant use of any drug that is a strong CYP3A inhibitor or inducer - Psychological, familial, sociological or geographical conditions that do not permit compliance with the study protocol - Life expectancy of less than 6 months - Pregnancy, lactation or planning to be pregnant. - Neo-adjuvant cohorts (Phase II): Prior therapy for breast cancer (medical, surgical or radiation therapy) - Neo-adjuvant cohorts (Phase II): Clinical T4 disease - Neo-adjuvant cohorts (Phase II): Inoperable or metastatic breast cancer based on standard evaluation |
Country | Name | City | State |
---|---|---|---|
United States | M D Anderson Cancer Center | Houston | Texas |
Lead Sponsor | Collaborator |
---|---|
M.D. Anderson Cancer Center |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Incidence of adverse events (Phase I) | Assessed continuously using Common Terminology Criteria for Adverse Events version 4.03, with physical examination and laboratory assessments. | Up to 30 days post-treatment | |
Primary | Change in breast tumor proliferation index (Ki67) (Phase II, Part I) | Will determine the dose responsiveness of 2 dose levels (400 mg and recommended phase 2 dose) of hydroxychloroquine added to low dose palbociclib and letrozole. | Baseline up to 30 days post-treatment | |
Primary | Change in autophagy (Phase II, Part I) | Will determine the dose responsiveness of 2 dose levels (400 mg and recommended phase 2 dose) of hydroxychloroquine added to low dose palbociclib and letrozole. | Baseline up to 30 days post-treatment | |
Primary | Change in senescence (Phase II, Part I) | Will determine the dose responsiveness of 2 dose levels (400 mg and recommended phase 2 dose) of hydroxychloroquine added to low dose palbociclib and letrozole. | Baseline up to 30 days post-treatment | |
Primary | Change in cell cycle control (Phase II, Part I) | Will determine the dose responsiveness of 2 dose levels (400 mg and recommended phase 2 dose) of hydroxychloroquine added to low dose palbociclib and letrozole. | Baseline up to 30 days post-treatment | |
Primary | Change in proportion of patients achieving tumoral complete cell cycle arrest (Phase II, Part II) | Defined as the Ki67 =< 2.7%. | At weeks 2 and 4 | |
Secondary | Longer term clinical tumor responsiveness (tumor volume) (Phase II Part I) | Up to 1 year | ||
Secondary | Tumor biomarker indices (for patients who have extended pre-operative therapy, maximum 24 weeks) (Phase II Part I and II) | Up to 1 year | ||
Secondary | Blood-based tumor protein, deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) biomarkers (Phase II Part I and II) | Will perform exploratory studies on blood-based tumor protein, DNA and RNA biomarkers with a focus on pathways of cell proliferation, autophagy, senescence and cell cycle control. | Up to 1 year | |
Secondary | Breast tumor indices of proliferation, autophagy, senescence, cell cycle control and other intersecting pathways (Phase II Part II) | Up to 1 year | ||
Secondary | Dose responsiveness hydroxychloroquine (400 mg versus recommended phase 2 dose) (Phase II Part II) | Up to 1 year |
Status | Clinical Trial | Phase | |
---|---|---|---|
Not yet recruiting |
NCT06113016 -
Prevention of Frailty With Fisetin and Exercise (PROFFi) in Breast Cancer Survivors
|
Phase 2 | |
Recruiting |
NCT05673200 -
Testing the Addition of an Anti-cancer Drug, ASTX727 (Cedazuridine, Decitabine), to Chemotherapy (Paclitaxel) and Immunotherapy (Pembrolizumab) for Metastatic Triple-Negative Breast Cancer
|
Phase 1 | |
Active, not recruiting |
NCT03218826 -
PI3Kbeta Inhibitor AZD8186 and Docetaxel in Treating Patients Advanced Solid Tumors With PTEN or PIK3CB Mutations That Are Metastatic or Cannot Be Removed by Surgery
|
Phase 1 | |
Completed |
NCT04535323 -
Platelet Rich Plasma for the Treatment of Genitourinary Syndrome of Menopause in Patients With Stage 0-III Breast Cancer
|
Phase 1 | |
Recruiting |
NCT05464810 -
Letrozole With and Without Simvastatin for the Treatment of Stage I-III Hormone Receptor Positive, HER2 Negative Breast Cancer
|
Early Phase 1 | |
Active, not recruiting |
NCT04249622 -
Rifaximin for the Treatment of Gastrointestinal Toxicities Related to Pertuzumab-Based Therapy in Patients With Stage I-III HER2 Positive Breast Cancer
|
Phase 2 | |
Withdrawn |
NCT03666819 -
Carbon Dioxide Fractional Laser in Treating Participants With Stage 0-III Hormone Receptor-Positive Breast Cancer With Vulvovaginal Atrophy
|
Phase 2 | |
Recruiting |
NCT04862585 -
Safely Stopping Pre-medications in Patients With Breast Cancer Who Are Receiving Paclitaxel
|
Phase 2/Phase 3 | |
Withdrawn |
NCT05967286 -
Olaparib and Alpelisib for Treatment of Metastatic Breast Cancer, A ComboMATCH Treatment Trial
|
Phase 2 | |
Recruiting |
NCT04593277 -
Interactive Survivorship Program for the Improvement of Healthcare Resources in Adolescent and Young Adult Cancer Survivors, INSPIRE-AYA Study
|
N/A | |
Active, not recruiting |
NCT05086731 -
Mobile Health to Improve Oral Chemotherapy Adherence Among Women With Breast Cancer
|
N/A | |
Recruiting |
NCT05368428 -
Transcutaneous Electrical Nerve Stimulation in Chemotherapy Induced Peripheral Neuropathy in Patients With Stage I-III Early Stage Breast Cancer
|
N/A | |
Recruiting |
NCT04673448 -
Niraparib and TSR-042 for the Treatment of BRCA-Mutated Unresectable or Metastatic Breast, Pancreas, Ovary, Fallopian Tube, or Primary Peritoneal Cancer
|
Phase 1 | |
Not yet recruiting |
NCT05539365 -
Dendritic Cell-Based Treatment Plus Immunotherapy for the Treatment of Metastatic or Unresectable Triple Negative Breast Cancer
|
Phase 2 | |
Active, not recruiting |
NCT04086875 -
A Text-based Intervention in Improving Adherence to Hormone Therapy in Patients With Stage I-III Hormone Receptor Positive Breast Cancer
|
N/A | |
Completed |
NCT00507923 -
Tibetan Yoga in Improving Fatigue and Sleep in Participants With Stage I-III Breast Cancer
|
N/A | |
Recruiting |
NCT06058377 -
Adding an Immunotherapy Drug, MEDI4736 (Durvalumab), to the Usual Chemotherapy Treatment (Paclitaxel, Cyclophosphamide, and Doxorubicin) for Stage II-III Breast Cancer
|
Phase 3 | |
Active, not recruiting |
NCT04514484 -
Testing the Combination of the Anti-cancer Drugs XL184 (Cabozantinib) and Nivolumab in Patients With Advanced Cancer and HIV
|
Phase 1 | |
Recruiting |
NCT05455658 -
STEMVAC in Patients With Early Stage Triple Negative Breast Cancer
|
Phase 2 | |
Recruiting |
NCT05674578 -
Health Coaching-Based Navigation at the Conclusion of Treatment for the Support of Black Breast Cancer Survivors
|
N/A |