PD0332991 + Anastrozole for Breast Cancer

Recruiting at 3 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

84 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug Anastrozole for breast cancer?

Anastrozole has been shown to be effective as a first-line treatment for advanced breast cancer in postmenopausal women, with studies indicating it is superior to tamoxifen in improving disease-free survival and time to recurrence for patients with hormone receptor-positive breast cancer. ^{1 2 3 4 5}

Is the combination of PD0332991 and Anastrozole safe for humans?

Anastrozole, also known as Arimidex, has been studied extensively and is generally considered safe for treating breast cancer in postmenopausal women, with side effects similar to other treatments like tamoxifen. However, specific safety data for the combination of PD0332991 and Anastrozole is not provided in the available research. ^{1 2 3 6 7}

How does the drug PD0332991 + Anastrozole differ from other breast cancer treatments?

The combination of PD0332991 (a CDK4/6 inhibitor) and Anastrozole (an aromatase inhibitor) is unique because it targets both cell cycle regulation and estrogen production, potentially offering a more comprehensive approach to treating hormone-sensitive breast cancer compared to using Anastrozole alone. ^{1 3 4 8 9}

What is the purpose of this trial?

A Phase II study to investigate the potential utility of PD 0332991 in the treatment of early stage ER+ Human epidermal growth factor receptor 2 (HER2)- breast cancer, to investigate whether the combination of PD 0332991 and anastrozole is able to: 1) improve the pathologic complete response rate when compared to the historical control of single agent aromatase inhibitors, 2) result in fewer patients with on therapy Ki67\>10% compared to historical control.

Research Team

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

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

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

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

Premenopausal, patient must be willing to comply with pregnancy requirements

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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 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, 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, 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]

References

1. England pubmed.ncbi.nlm.nih.gov

Anastrozole: pharmacological and clinical profile in postmenopausal women with breast cancer. [2018]

2. United States 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. [2022]

3. England 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. [2022]

4. United States 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. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Retrospective analysis of time to recurrence in the ATAC trial according to hormone receptor status: an hypothesis-generating study. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Influence of comorbidities and age on risk of death without recurrence: a retrospective analysis of the Arimidex, Tamoxifen Alone or in Combination trial. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Phase II trial of anastrozole in women with asymptomatic müllerian cancer. [2019]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Arimidex inhibition on proliferation of human breast solid tumors measured by ATP bioluminescence. [2018]

9. Cyprus pubmed.ncbi.nlm.nih.gov

The effects of anastrozole on the proliferation of FM3A cells. [2018]