Capivasertib + Paclitaxel for Breast Cancer

(CAPItello-290 Trial)

Recruiting at 218 trial locations

Overseen By AZ Breast Cancer Study Navigators BreastCancerStudyLocator.com

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must not be taking: AKT inhibitors, PI3K inhibitors

Disqualifiers: Recent chemotherapy, Cardiac issues, Diabetes, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: 28-day cycles, repeated

923 Participants Needed

Trial Summary

What is the purpose of this trial?

Phase III Study of Capivasertib + Paclitaxel versus Placebo + Paclitaxel as First line Treatment for Patients with Locally Advanced or Metastatic Triple-negative Breast Cancer (TNBC)

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before starting, such as AKT, PI3K, and mTOR inhibitors, and any chemotherapy, immunotherapy, or immunosuppressant medications within 3 weeks of the first dose. You also need to avoid potent inhibitors or inducers of CYP3A4 within 2 weeks prior to the first dose.

What data supports the effectiveness of the drug Capivasertib + Paclitaxel for breast cancer?

Paclitaxel has been shown to be effective in treating metastatic breast cancer, with significant antitumor activity and a well-documented safety profile. Additionally, combining paclitaxel with other drugs like bevacizumab has demonstrated a high response rate and prolonged progression-free survival in similar cases. ^{1 2 3 4 5}

Is the combination of Capivasertib and Paclitaxel safe for humans?

Paclitaxel, a drug used in combination with Capivasertib, has been shown to have a demonstrated safety profile in treating breast cancer, with less toxicity in its newer formulation (nab-paclitaxel) compared to the traditional form. It has been approved by the FDA for use in breast cancer, indicating it is generally considered safe for humans. ^{3 6 7 8 9}

What makes the Capivasertib + Paclitaxel treatment unique for breast cancer?

This treatment combines Capivasertib, a newer drug that targets specific cancer cell pathways, with Paclitaxel, a well-established chemotherapy drug known for its effectiveness in breast cancer. The combination aims to enhance the overall treatment effect by attacking cancer cells in different ways. ^{1 3 10 11 12}

Research Team

Peter Schmid, MD,PhD,FRCP

Principal Investigator

Centre for Experimental Cancer Medicine (CECM), Barts Cancer Institute

Eligibility Criteria

This trial is for adults with advanced or metastatic Triple-negative Breast Cancer (TNBC) who haven't had certain recent treatments. They should be relatively fit, have a tumor sample available, and not planning surgery to remove the cancer. People can't join if they've had specific drugs recently, including chemotherapy within 6 months, AKT/PI3K/mTOR inhibitors, or are experiencing significant neuropathy.

Inclusion Criteria

My cancer can be measured or seen on scans.

FFPE tumour sample from primary/recurrent cancer

My cancer has spread or returned and cannot be removed with surgery.

Exclusion Criteria

Prior treatment with any of the treatments listed below. Patients are not eligible to enter the study if they have received any of the medications specified below or are unable to meet the cautions and restrictions: AKT, PI3K, and/or mTOR inhibitors; Capivasertib in the present study (ie, any dosing with capivasertib due to previous participation in this study); Any other chemotherapy, immunotherapy, immunosuppressant medication (other than corticosteroids) or anticancer agents within 3 weeks of the first dose of study treatment. A longer washout may be required for drugs with a long halflife (eg, biologics) as agreed by the sponsor; Potent inhibitors or inducers of CYP3A4 within 2 weeks prior to the first dose of study treatment (3 weeks for St John's wort), or drugs that are sensitive to CYP3A4 inhibition within 1 week prior to the first dose of study treatment; Radiotherapy with a wide field of radiation within 4 weeks before the first dose of study treatment (capivasertib/placebo); Pre-existing sensory or motor polyneuropathy ≥grade 2 according to NCI CTCAE v5; With the exception of alopecia, any unresolved toxicities from prior therapy greater than CTCAE grade 1 at the time of starting study treatment

I have had treatment for cancer that couldn't be removed by surgery.

I finished chemotherapy less than 6 months ago, or taxane chemotherapy less than 12 months ago.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Capivasertib + Paclitaxel or Placebo + Paclitaxel. Paclitaxel is administered as intravenous infusions weekly for 3 weeks followed by 1 week off, and Capivasertib or Placebo is taken orally on an intermittent weekly schedule.

28-day cycles, repeated

Weekly visits for infusions

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments including clinical benefit rate, overall survival, and progression-free survival.

Up to approximately 42 months

Treatment Details

Interventions

• Capivasertib
• Paclitaxel
• Placebo

Trial Overview The study compares Capivasertib combined with Paclitaxel against a placebo plus Paclitaxel in treating TNBC. It's a Phase III trial where patients are randomly assigned to either treatment group as their first line of therapy.

Participant Groups

Group I: Capivasertib + Paclitaxel Experimental Treatment 2 Interventions

Paclitaxel: Intravenous infusion. 3 consecutive weekly infusions of 80 mg/m2 (given on Day 1 of Weeks 1, 2, and 3), followed by 1 week off-treatment within each 28-day treatment cycle. Capivasertib: Oral tablets. 400 mg of Capivasertib (2 tablets) BD given on an intermittent weekly dosing schedule. Dosed on Days 2 to 5 of Weeks 1, 2, and 3 followed by 1 week off-treatment within each 28-day treatment cycle.

Group II: Placebo + Paclitaxel Placebo Group 2 Interventions

Paclitaxel: Intravenous infusion. 3 consecutive weekly infusions of 80 mg/m2 (given on Day 1 of Weeks 1, 2, and 3), followed by 1 week off-treatment within each 28-day treatment cycle. Placebo: Oral tablets. 400 mg of Placebo (2 tablets) BD given on an intermittent weekly dosing schedule. Dosed on Days 2 to 5 of Weeks 1, 2, and 3 followed by 1 week off-treatment within each 28-day treatment cycle.

Capivasertib is already approved in United States, European Union for the following indications:

Approved in United States as Truqap for:

• Hormone receptor-positive, HER2-negative locally advanced or metastatic breast cancer with one or more PIK3CA/AKT1/PTEN-alterations

Approved in European Union as Truqap for:

• Locally advanced or metastatic breast cancer with one or more PIK3CA/AKT1/PTEN alterations

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Findings from Research

In a study of 30 women with advanced breast cancer, the combination of doxorubicin and paclitaxel resulted in a high overall response rate of 83%, with 24% achieving complete remission, indicating strong efficacy for this treatment regimen.

However, the treatment was associated with significant toxicities, including neutropenia and cardiotoxicity, with 50% of patients experiencing reduced heart function and 20% developing congestive heart failure, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined doxorubicin and paclitaxel in advanced breast cancer: effective and cardiotoxic. Gehl, J., Boesgaard, M., Paaske, T., et al.[2020]

A panel of expert oncologists reached consensus that the combination of bevacizumab and paclitaxel is effective as a first-line treatment for HER2-negative metastatic breast cancer, showing a significant progression-free survival benefit compared to paclitaxel alone.

Despite the absence of an overall survival benefit in clinical trials, the panel acknowledged the regimen's effectiveness and safety based on real-world data, although opinions varied on its use in specific patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Delphi consensus and open debate on the role of first-line bevacizumab for HER2-negative metastatic breast cancer. Puglisi, F., Bisagni, G., Ciccarese, M., et al.[2017]

In a study involving 255 metastatic breast cancer patients, maintenance therapy with paclitaxel did not significantly improve progression-free survival compared to no additional chemotherapy, with median times of 8.0 months versus 9.0 months, respectively.

The study was halted early due to a futility analysis indicating only an 8.6% chance of achieving a meaningful improvement in survival, suggesting that additional paclitaxel treatment after initial chemotherapy may not be beneficial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lack of benefit of maintenance paclitaxel in first-line chemotherapy in metastatic breast cancer. Gennari, A., Amadori, D., De Lena, M., et al.[2015]

A 68-year-old woman with metastatic breast cancer who was resistant to taxane treatment showed a partial response when treated with a combination of weekly paclitaxel and bevacizumab, indicating potential effectiveness of this regimen in taxane-resistant cases.

This case suggests that combining bevacizumab with taxanes may provide a valuable treatment option for patients with metastatic breast cancer who have developed resistance to standard taxane therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel-resistant advanced recurrent breast cancer: a case of partial response due to addition of bevacizumab to paclitaxel therapy: a case report. Ishizuna, K., Ninomiya, J., Kojima, M., et al.[2021]

Nab-paclitaxel (Abraxane(®)) has been approved by the FDA for treating breast cancer after chemotherapy failure, showing superior efficacy compared to traditional paclitaxel (Taxol(®)).

This new formulation not only demonstrates better effectiveness but also has less toxicity, which enhances its safety profile and therapeutic index, making it a promising option for combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nab-paclitaxel in the treatment of metastatic breast cancer: a comprehensive review. Montero, AJ., Adams, B., Diaz-Montero, CM., et al.[2021]

In a study involving 74 patients with metastatic melanoma, nab-Paclitaxel showed a response rate of 21.6% in chemotherapy-naive patients and 2.7% in previously treated patients, indicating better efficacy in those who had not undergone prior treatment.

The treatment was well tolerated, with 78% of previously treated patients and 49% of chemotherapy-naive patients able to complete therapy without dose reductions, suggesting a favorable safety profile compared to standard therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 2 clinical trial of nab-paclitaxel in previously treated and chemotherapy-naive patients with metastatic melanoma. Hersh, EM., O'Day, SJ., Ribas, A., et al.[2020]

Paclitaxel (Taxol) is a significant new chemotherapy drug for breast cancer, showing promise in both single-agent and combination treatments.

Ongoing research at Memorial Sloan-Kettering Cancer Center aims to optimize the use of paclitaxel in various treatment settings, including metastatic and adjuvant therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Memorial Sloan-Kettering Cancer Center experience with paclitaxel in the treatment of breast cancer. Seidman, AD., Hudis, CA., Fennelly, D., et al.[2015]

In a study of 40 patients with HER2-positive metastatic breast cancer, the combination of trastuzumab, paclitaxel, and capecitabine resulted in a high overall response rate of 81.1%, with 24.3% achieving complete responses and 56.8% partial responses.

The treatment was well-tolerated, with manageable grade 3 adverse events, indicating that this combination therapy is both effective and safe for first-line treatment in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and toxicity of Trastuzumab and Paclitaxel plus Capecitabine in the first-line treatment of HER2-positive metastatic breast cancer. Tonyali, O., Benekli, M., Berk, V., et al.[2021]

References

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

Combined doxorubicin and paclitaxel in advanced breast cancer: effective and cardiotoxic. [2020]

2. England pubmed.ncbi.nlm.nih.gov

A Delphi consensus and open debate on the role of first-line bevacizumab for HER2-negative metastatic breast cancer. [2017]

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

Memorial Sloan-Kettering Cancer Center experience with paclitaxel in the treatment of breast cancer: from advanced disease to adjuvant therapy. [2015]

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

Lack of benefit of maintenance paclitaxel in first-line chemotherapy in metastatic breast cancer. [2015]

5. England pubmed.ncbi.nlm.nih.gov

Paclitaxel-resistant advanced recurrent breast cancer: a case of partial response due to addition of bevacizumab to paclitaxel therapy: a case report. [2021]

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

Paclitaxel in breast cancer. [2016]

7. England pubmed.ncbi.nlm.nih.gov

Nab-paclitaxel in the treatment of metastatic breast cancer: a comprehensive review. [2021]

8. China pubmed.ncbi.nlm.nih.gov

[Paclitaxel (Tesu) as a single agent in the treatment of breast cancer]. [2015]

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

A phase 2 clinical trial of nab-paclitaxel in previously treated and chemotherapy-naive patients with metastatic melanoma. [2020]

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

Memorial Sloan-Kettering Cancer Center experience with paclitaxel in the treatment of breast cancer. [2015]

11. England pubmed.ncbi.nlm.nih.gov

Cutaneous photosensitivity induced by paclitaxel and trastuzumab therapy associated with aberrations in the biosynthesis of porphyrins. [2015]

12. Germany pubmed.ncbi.nlm.nih.gov

Efficacy and toxicity of Trastuzumab and Paclitaxel plus Capecitabine in the first-line treatment of HER2-positive metastatic breast cancer. [2021]