Capivasertib + Paclitaxel for Breast Cancer

(CAPItello-290 Trial)

Not currently recruiting at 278 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment combination for individuals with a specific type of breast cancer called triple-negative breast cancer (TNBC) that has spread or cannot be surgically removed. Researchers aim to determine if adding Capivasertib, an experimental drug, to the standard chemotherapy drug Paclitaxel can improve outcomes compared to Paclitaxel with a placebo (a pill with no active medication). This trial is suitable for those with TNBC who cannot undergo surgery to remove the cancer. Participants should not have received certain treatments before, such as chemotherapy for advanced cancer or specific types of medications. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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.

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

Research shows that combining Capivasertib with Paclitaxel is generally well-tolerated. One study found that the side effects of this combination resemble those seen when each drug is used alone.

Capivasertib pairs well with Paclitaxel, a common chemotherapy drug. Previous trials reported some expected side effects, such as tiredness and nausea, but these were manageable. This suggests that the treatment is relatively safe for patients.

Capivasertib is being tested with Paclitaxel specifically for triple-negative breast cancer (TNBC). While more research is needed to fully understand the long-term safety, current data offers promising evidence of its tolerability. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for breast cancer?

Researchers are excited about Capivasertib in combination with Paclitaxel for breast cancer because it offers a unique approach to treatment. Unlike standard therapies that typically target cancer cell growth in general, Capivasertib specifically inhibits the AKT pathway, which is crucial for cancer cell survival and proliferation. This targeted action has the potential to enhance the effectiveness of Paclitaxel, a well-established chemotherapy, by making cancer cells more susceptible to its effects. Additionally, the oral administration of Capivasertib provides a more convenient treatment option compared to other intravenous therapies, potentially improving patient compliance and quality of life.

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

In this trial, participants will receive either a combination of capivasertib with paclitaxel or a placebo with paclitaxel. Research has shown that capivasertib with paclitaxel may help treat triple-negative breast cancer (TNBC). One study found that this combination allowed patients to live longer without their cancer worsening and improved overall survival compared to paclitaxel alone. Capivasertib blocks a protein that aids cancer cell growth. In TNBC, which is often aggressive, this targeted approach can help slow the disease. Although more research is needed, these findings suggest the combination might be effective for this challenging cancer. ^{2 3 4 5 6}

Who Is on the Research Team?

Peter Schmid, MD,PhD,FRCP

Principal Investigator

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

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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]

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]

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11365631/

Efficacy and safety analysis of AKT inhibitor in triple- ... AKT inhibitors showed slightly better efficacy in the treatment of TNBC. However, further studies are needed to evaluate its long-term safety and optimal ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02423603

PAKT: AZD5363 in Combination With Paclitaxel in Triple- ... Capivasertib Plus Paclitaxel Versus Placebo Plus Paclitaxel As First-Line Therapy for Metastatic Triple-Negative Breast Cancer: The PAKT Trial. J Clin Oncol ...

3. astrazeneca.com astrazeneca.com/media-centre/press-releases/2024/update-on-capitello-290-phase-iii-trial.html

Update on the CAPItello-290 Phase III trial for Truqap plus ... While the CAPItello-290 trial results have not shown what we hoped, they provide important information to further understand this aggressive ...

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa2214131

Capivasertib in Hormone Receptor–Positive Advanced ... In the overall population, the median progression-free survival was 7.2 months in the capivasertib–fulvestrant group, as compared with 3.6 ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2018.36.15_suppl.1007

AZD5363 plus paclitaxel versus placebo ... Conclusions: The trial met its primary endpoint. Addition of AZD5363 to 1st-line paclitaxel therapy for TNBC resulted in significantly longer PFS and OS.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT01625286

Investigating Safety, Tolerability and Efficacy of AZD5363 ... The purpose of this study is to investigate the safety and efficacy of different doses and schedules of AZD5363, when in combination with paclitaxel, ...