PD0332991 + Anastrozole for Breast Cancer

Not currently recruiting at 4 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Washington University School of Medicine

Must be taking: Endocrine therapy

Must not be taking: Cdk4 inhibitors, Anticoagulants, CYP3A4 inhibitors, CYP3A4 inducers

Disqualifiers: Metastatic disease, HIV, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for early-stage breast cancer that is ER+ (estrogen receptor-positive) and HER2- (human epidermal growth factor receptor 2-negative). Researchers are testing whether combining PD 0332991, a potential new drug, with anastrozole can improve treatment outcomes compared to anastrozole alone. Participants are divided into groups based on specific genetic markers and previous treatment responses. Women with ER+ and HER2- breast cancer who have not yet undergone surgery, radiation, or chemotherapy might be suitable candidates. The trial aims to determine if this combination can better control the cancer before surgery. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires that you do not use certain medications that are strong CYP3A4 inhibitors or inducers, such as grapefruit juice, certain antibiotics, and some other drugs. If you are taking any of these, you may need to stop or switch medications before participating.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that patients generally tolerate the combination of palbociclib and anastrozole well. In earlier studies, some patients experienced side effects such as tiredness and low white blood cell counts, but these were mostly manageable. Some needed to adjust doses or take breaks from treatment due to these effects, yet many continued treatment successfully.

The FDA has already approved palbociclib for other types of breast cancer, indicating its well-known safety profile. Anastrozole is also a common breast cancer treatment. Together, these drugs have demonstrated a promising safety record, making them a viable option for those considering joining a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of PD 0332991 and anastrozole for breast cancer because it offers a new way to tackle the disease. While standard treatments often include hormone therapy or chemotherapy, PD 0332991, also known as palbociclib, works by inhibiting specific proteins called CDK4/6, which are crucial for cancer cell growth. This mechanism is unique compared to typical hormone therapies that target hormone receptors directly. Additionally, the combination with anastrozole, an aromatase inhibitor, aims to enhance the treatment's effectiveness by further reducing estrogen levels, potentially leading to better outcomes for patients, especially those with specific genetic mutations like PIK3CA.

What evidence suggests that this trial's treatments could be effective for breast cancer?

Research has shown that using PD 0332991 (palbociclib) with anastrozole can help treat estrogen receptor-positive (ER+) breast cancer. In this trial, participants will receive PD 0332991 combined with anastrozole, and some may also receive goserelin if premenopausal. Studies have found that adding palbociclib to hormone treatments like fulvestrant helps patients live longer without their cancer growing or spreading. When combined with letrozole, another hormone treatment, palbociclib improves patient response. Anastrozole works by reducing estrogen levels, which can slow the growth of certain breast cancers. Together, these treatments aim to fight breast cancer more effectively than hormone therapy alone. ^{1 3 4 6 7}

Who Is on the Research Team?

Cynthia X Ma, M.D., Ph.D.

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

This trial is for premenopausal women over 18 with early-stage ER+ HER2- breast cancer, who have not received prior treatment for this cancer. They must be willing to use contraception and have a life expectancy over 4 months. Participants need adequate organ function and no history of certain cancers or conditions that would interfere with the study.

Inclusion Criteria

Premenopausal, patient must be willing to comply with pregnancy requirements

I can take care of myself and am up and about more than half of my waking hours.

My last blood test shows I am in menopause.

Exclusion Criteria

I have had a condition where my lymphocytes grow abnormally.

I have a history of cancer.

I haven't had cancer in the last 5 years, except for skin cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive PD 0332991 combined with anastrozole (and goserelin if premenopausal) for 4 cycles of 28 days each, followed by a 5th cycle of 10-12 days

16-18 weeks

Cycle 1 Day 15 visit for tumor biopsy

Surgery

Standard surgery performed per institutional standards 2-4 weeks following the completion of Cycle 4 or on Day 11, 12, or 13 of Cycle 5

2-4 weeks after treatment

Adjuvant Therapy

Participants who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated

23 cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Anastrozole
• PD 0332991
• Surgery
• Tumor biopsy

Trial Overview The trial tests if PD0332991 combined with anastrozole improves response rates in breast cancer compared to aromatase inhibitors alone. It also checks if fewer patients have high levels of Ki67, indicating cell proliferation, after treatment. The study includes surgery as standard care and tumor biopsies.

How Is the Trial Designed?

Group I: Arm 3: Endocrine Resistant Cohort Experimental Treatment 5 Interventions

* Tumor biopsy for testing/research at baseline and Cycle 1 Day 15 * Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery) * Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5. * Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.

Group II: Arm 2: PIK3CA Mutant Type Cohort Experimental Treatment 5 Interventions

* Tumor biopsy for testing/research at baseline and Cycle 1 Day 15 * Cycle 0 is 28 days of anastrozole PO daily and, if premenopausal, goserelin SC every 28 days. * Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery) * Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5. * Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.

Group III: Arm 1: PIK3CA Wild Type Cohort Experimental Treatment 5 Interventions

* Tumor biopsy for testing/research at baseline and Cycle 1 Day 15 * Cycle 0 is 28 days of anastrozole PO daily and, if premenopausal, goserelin SC every 28 days. * Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery) * Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5. * Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.

Anastrozole is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Arimidex for:

• Breast cancer
• Early breast cancer in postmenopausal women

Approved in United States as Arimidex for:

• Adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer
• First-line treatment of postmenopausal women with hormone receptor-positive or hormone receptor unknown locally advanced or metastatic breast cancer

Approved in Canada as Arimidex for:

• Adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer
• Treatment of postmenopausal women with hormone receptor-positive advanced breast cancer

Approved in Japan as Arimidex for:

• Breast cancer

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Pfizer

Industry Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Published Research Related to This Trial

Anastrozole, a selective aromatase inhibitor, was evaluated in a phase II trial involving 53 women with recurrent müllerian cancer, showing modest toxicity and primarily resulting in stable disease rather than significant tumor shrinkage.

While 42% of patients experienced stable disease for over 90 days, the overall tumoricidal activity was minimal, indicating that anastrozole may not be effective as a primary treatment for this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of anastrozole in women with asymptomatic müllerian cancer. del Carmen, MG., Fuller, AF., Matulonis, U., et al.[2019]

Anastrozole is as effective as tamoxifen for treating advanced breast cancer in postmenopausal women, showing a slightly higher objective response rate (21% vs. 17%) and a significant clinical benefit in 59% of patients compared to 46% for tamoxifen.

Anastrozole offers a significant advantage in time to progression (median of 11.1 months vs. 5.6 months for tamoxifen) and has a lower incidence of side effects, such as thromboembolic events and vaginal bleeding, making it a preferable first-line therapy option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anastrozole is superior to tamoxifen as first-line therapy for advanced breast cancer in postmenopausal women: results of a North American multicenter randomized trial. Arimidex Study Group. Nabholtz, JM., Buzdar, A., Pollak, M., et al.[2022]

Anastrozole, an aromatase inhibitor, significantly reduced cell viability and proliferation in estrogen receptor-positive FM3A cells, indicating its potential effectiveness in treating estrogen-sensitive breast cancer.

The study identified a dose of 1μM as the most effective for inhibiting cell growth, with statistically significant results across all tested doses and time points, suggesting a strong antiproliferative effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of anastrozole on the proliferation of FM3A cells. Topcul, M., Cetin, I., Ozlem Kolusayin Ozar, M.[2018]

In a study of 6241 postmenopausal women with early-stage breast cancer, anastrozole was found to have significantly fewer treatment-related adverse events compared to tamoxifen, indicating better tolerability.

Anastrozole also demonstrated a more favorable risk-benefit profile, with lower rates of serious adverse events and recurrence compared to tamoxifen, making it a preferable option for adjuvant treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comprehensive side-effect profile of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: long-term safety analysis of the ATAC trial. Buzdar, A., Howell, A., Cuzick, J., et al.[2022]

Anastrozole is a potent and selective third-line aromatase inhibitor that offers a significant advancement in the treatment of hormone-sensitive breast cancer, particularly for postmenopausal women.

This review highlights anastrozole's biochemical properties and clinical efficacy, indicating its widespread use as a first- and second-line treatment option, potentially providing better outcomes and safety compared to traditional therapies like tamoxifen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anastrozole: pharmacological and clinical profile in postmenopausal women with breast cancer. Köberle, D., Thürlimann, B.[2018]

In a study involving 668 postmenopausal women with advanced breast cancer, anastrozole was found to be as effective as tamoxifen, with similar median time to progression (8.2 months for anastrozole vs. 8.3 months for tamoxifen).

Anastrozole demonstrated a lower incidence of side effects, such as thromboembolic events (4.8% vs. 7.3%) and vaginal bleeding (1.2% vs. 2.4%), suggesting it may be a safer first-line treatment option for advanced breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anastrozole versus tamoxifen as first-line therapy for advanced breast cancer in 668 postmenopausal women: results of the Tamoxifen or Arimidex Randomized Group Efficacy and Tolerability study. Bonneterre, J., Thürlimann, B., Robertson, JF., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9553912/

Real-world study of overall survival with palbociclib plus ... The 5-year survival rate for de novo MBC is only 29.0%. The majority (68%) of breast cancer cases have a hormone receptor–positive (HR+)/human ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa1505270

Palbociclib in Hormone-Receptor–Positive Advanced ... Palbociclib combined with fulvestrant resulted in longer progression-free survival than fulvestrant alone.

3. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2012-02202

PD 0332991 and Anastrozole for Stage 2 or 3 Estrogen ... Hormone therapy using anastrozole may fight breast cancer by lowering the amount of estrogen the body makes. Giving palbociclib isethionate together with ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT01684215

NCT01684215 | A Study Of Oral Palbociclib (PD-0332991), ... Palbociclib-letrozole as first-line treatment for advanced breast cancer: Updated results from a Japanese phase 2 study. Cancer Med. 2020 Jul;9(14):4929 ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4924326/

Efficacy and safety of palbociclib in combination with ... A clinically meaningful improvement in median PFS and clinical benefit response (CBR) rate was seen with palbociclib + letrozole in every subgroup evaluated.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8569699/

Palbociclib in combination with aromatase inhibitors ... Palbociclib is a safe and effective treatment in patients ≥75 years. · Higher rates of treatment discontinuation and dose reductions were noted.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4537809/

Palbociclib for the Treatment of Estrogen Receptor ... CDK 4/6 inhibitor palbociclib (PD0332991) in Rb+ advanced breast cancer: phase II activity, safety, and predictive biomarker assessment. Clin Cancer Res.