Shorter Chemo-Immunotherapy Without Anthracyclines for Breast Cancer
Recruiting in Palo Alto (17 mi)
+432 other locations
Overseen byPriyanka Sharma
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: SWOG Cancer Research Network
Must not be taking: Anti-PD-1, Anti-PD-L1
Disqualifiers: Metastatic disease, Uncontrolled diabetes, others
No Placebo Group
Pivotal Trial (Near Approval)
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This phase III trial compares the effects of shorter chemotherapy (chemo)-immunotherapy without anthracyclines to usual chemo-immunotherapy for the treatment of early-stage triple negative breast cancer. Paclitaxel is in a class of medications called anti-microtubule agents. It stops cancer cells from growing and dividing and may kill them. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of cancer cells. Cyclophosphamide is in a class of medications called alkylating agents. It works by damaging the cell's deoxyribonucleic acid (DNA) and may kill cancer cells. It may also lower the body's immune response. Docetaxel is in a class of medications called taxanes. It stops cancer cells from growing and dividing and may kill them. Doxorubicin is an anthracycline chemotherapy drug that damages DNA and may kill cancer cells. Pembrolizumab may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Shorter treatment without anthracycline chemotherapy may work the same as the usual anthracycline chemotherapy treatment for early-stage triple negative breast cancer.
Will I have to stop taking my current medications?
The trial information does not specify whether you need to stop taking your current medications. However, you cannot use other investigational agents or have uncontrolled diabetes or hypertension. It's best to discuss your specific medications with the trial team.
What data supports the effectiveness of the drug combination used in the clinical trial for breast cancer?
Research shows that docetaxel, one of the drugs in the trial, has a high response rate of about 60% in treating metastatic breast cancer and is superior to doxorubicin in terms of response rate. Additionally, combinations of doxorubicin with taxanes like docetaxel have shown impressive response rates in advanced breast cancer, suggesting potential effectiveness in the trial's drug combination.
12345Is the combination of doxorubicin and docetaxel safe for breast cancer treatment?
The combination of doxorubicin and docetaxel has been studied for breast cancer treatment and is generally considered safe, with the main concern being neutropenia (a low level of white blood cells), which can lead to infections. However, significant heart-related side effects (cardiotoxicity) were not observed, making it a viable option for many patients.
678910What makes the drug combination of Cyclophosphamide, Docetaxel, Doxorubicin, Paclitaxel, and Pembrolizumab unique for breast cancer treatment?
This treatment is unique because it combines multiple drugs, including docetaxel and pembrolizumab, which have shown high activity in breast cancer, without using anthracyclines, which are known for their heart-related side effects. This approach aims to maintain effectiveness while potentially reducing the risk of heart damage associated with traditional anthracycline-based therapies.
1361112Eligibility Criteria
This trial is for adults with early-stage triple negative breast cancer who haven't had systemic or radiation therapy, or breast surgery for their current cancer. They must have good heart function and no severe allergies to the study drugs. Participants can't be pregnant/nursing and must agree to use contraception. No live vaccines 30 days before joining, no uncontrolled diseases like diabetes or hypertension, and they shouldn't have a history of certain infections or other cancers that could affect the trial.Inclusion Criteria
I have never needed steroids for non-infectious lung inflammation.
Participants must not be currently participating in or have participated in a study of an investigational agent or used an investigational device within 28 days prior to randomization
I am 18 years old or older.
+44 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive neoadjuvant chemotherapy with pembrolizumab, followed by surgery. Arm I includes paclitaxel, carboplatin, doxorubicin, and cyclophosphamide. Arm II includes docetaxel and carboplatin.
Up to 18 months
Follow-up
Participants are monitored for safety and effectiveness after treatment
5 years
Every 6 months for the first 2 years, then annually
Optional Pembrolizumab Extension
Participants may receive pembrolizumab after surgery
Participant Groups
The trial tests if shorter chemo-immunotherapy without anthracycline drugs (like Doxorubicin) is as effective as usual treatment in early-stage triple negative breast cancer. It involves medications such as Paclitaxel, Carboplatin, Cyclophosphamide, Docetaxel, and Pembrolizumab which target different aspects of cancer cell growth.
2Treatment groups
Experimental Treatment
Active Control
Group I: Arm II (shorter chemo-immunotherapy)Experimental Treatment7 Interventions
Patients receive docetaxel IV, carboplatin IV, and pembrolizumab IV on study. Patients then undergo surgery. Patients may receive pembrolizumab after surgery. Patients may optionally undergo collection of blood samples throughout the trial.
Group II: Arm I (usual chemo-immunotherapy)Active Control9 Interventions
Patients receive paclitaxel IV, carboplatin IV, and pembrolizumab IV on study. Patients then receive doxorubicin IV, cyclophosphamide IV, and pembrolizumab IV on study. Patients then undergo surgery. Patients may receive pembrolizumab after surgery. Patients may optionally undergo collection of blood samples throughout the trial.
Cyclophosphamide is already approved in United States, European Union, Canada, Japan for the following indications:
🇺🇸 Approved in United States as Cytoxan for:
- Breast cancer
- Ovarian cancer
- Multiple myeloma
- Leukemia
- Lymphoma
- Rheumatoid arthritis
🇪🇺 Approved in European Union as Endoxan for:
- Breast cancer
- Ovarian cancer
- Multiple myeloma
- Leukemia
- Lymphoma
- Rheumatoid arthritis
🇨🇦 Approved in Canada as Neosar for:
- Breast cancer
- Ovarian cancer
- Multiple myeloma
- Leukemia
- Lymphoma
- Rheumatoid arthritis
🇯🇵 Approved in Japan as Endoxan for:
- Breast cancer
- Ovarian cancer
- Multiple myeloma
- Leukemia
- Lymphoma
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Hickman Cancer CenterAdrian, MI
Crossroads Cancer CenterEffingham, IL
Central Care Cancer Center - Garden CityGarden City, KS
Greater Regional Medical CenterCreston, IA
More Trial Locations
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Who Is Running the Clinical Trial?
SWOG Cancer Research NetworkLead Sponsor
National Cancer Institute (NCI)Collaborator
References
Compilation of phase I and II trial data of docetaxel and doxorubicin in the treatment of advanced breast cancer and other malignancies. [2018]Doxorubicin and docetaxel (Taxotere; Rhône-Poulenc Rorer, Antony, France) are the most active cytotoxic agents in the treatment of advanced breast cancer. In the pre-taxane era, randomized trials demonstrated that doxorubicin-containing chemotherapy regimens are associated with higher response rates and improved survival compared with non-doxorubicin-containing regimens. Doxorubicin-containing regimens were therefore considered the standard of care at that time. Because of the substantial activity of the taxanes in anthracyline-resistant breast cancer, there is a clear rationale for combining doxorubicin with the taxanes as initial therapy for patients with metastatic disease. The combination of doxorubicin plus paclitaxel has been extensively studied. Impressive response rates were noted in at least two studies, although the treatment also resulted in an unacceptably high risk of congestive heart failure. Paclitaxel is known to perturb the metabolism of doxorubicin, thereby increasing drug exposure and augmenting the cardiotoxicity of the anthracycline. The cardiotoxicity of the combination may be ameliorated by restricting the cumulative doxorubicin dose to less than 360 mg/m2, by increasing the interval between administration of the two drugs to at least 4 hours, or by adding the cardioprotective agent dexrazoxane. The Eastern Cooperative Oncology Group performed a randomized phase III trial comparing doxorubicin alone, paclitaxel alone, or the doxorubicin/paclitaxel combination in patients with metastatic breast cancer. Although the response rate and time to treatment failure improved with the combination, survival did not. There have been two phase II trials investigating the combination of doxorubicin plus docetaxel. The regimen was highly effective and did not seem to be associated with an increased risk of congestive heart failure. These findings justify further evaluation of the doxorubicin/docetaxel combination in patients with advanced and operable breast cancer. Such trials are currently in progress and will define the role for this combination in the management of patients with breast cancer.
[Chemotherapy of metastatic breast cancer]. [2009]The most powerful prognostic factor in the treatment of metastatic breast cancer continues to be the response to induction chemotherapy. The range of drugs which are widely used in the treatment of advanced disease, the anthracyclines, the taxanes and vinorelbine, have all shown interesting activity in terms of their ability to obtain both high response rates and long duration of response. The anthracyclines, doxorubicin (DX) and epiadriamycin (EPI) constitute the established reference agents in the treatment of metastatic disease, and combinations of these drugs with vinorelbine (VRB) and the taxanes, paclitaxel (PTX) and docetaxel (DCT), have produced major increases in objective response rates: PTX-DX (58%), DCT-EPI (69.4%), PTX-EPI (71.1%), VRB-DX (75%), VRB-EPI (77.1%). Suggestions for other combinations of chemotherapeutic agents which do not include anthracyclines available with well tolerated and effective drugs. The way forward after a response has been obtained remains an open question in which the limited efficacy of the available drugs and their cumulative toxicity needs to be balanced against the quality of life of patients during their disease. Defining the optimal strategy for the management of disease after induction treatment is a problem which needs to draw on the results of research, analysis of experience and insight into the needs of patients.
A review of the efficacy and safety of docetaxel as monotherapy in metastatic breast cancer. [2018]To date, although statistically significant, the overall impact of adjuvant chemotherapy on the survival of women with nonmetastatic breast cancer has been disappointing. Hence, new agents that have shown good activity against metastatic disease should be assessed quickly in the adjuvant setting. Docetaxel (Taxotere; Rhône-Poulenc Rorer, Antony, France) is one of the most promising drugs that has emerged in recent years, with phase II studies in previously untreated metastatic breast cancer indicating a high overall response rate of approximately 60%. A recent large, randomized comparison demonstrated docetaxel to be superior to doxorubicin with regard to response rate, and it is the only agent to have shown this superiority. Docetaxel was also tolerated better. A second randomized trial in patients who had already failed an anthracycline-containing regimen showed that docetaxel-treated patients survived significantly longer than those treated with the combination of mitomycin C and vinblastine. The apparent superiority of docetaxel over doxorubicin and the lack of complete cross-resistance between these drugs, which has been demonstrated in trials involving anthracycline-resistant patients, suggest a possible future role for docetaxel, either alone or in combination with the anthracycline, in earlier stages of metastatic breast cancer and indeed in the adjuvant treatment of early stage disease. The combination of docetaxel with doxorubicin appears particularly promising in this regard and, unlike the doxorubicin/paclitaxel doublet, has not been reported to produce clinically significant cardiomyopathy. The high activity of docetaxel provides a compelling rationale for its study as a component of adjuvant therapies. Investigators in Brussels and Dublin have recently demonstrated the feasibility of two candidate adjuvant programs. Large phase II adjuvant trials involving docetaxel are now being assessed.
New developments in chemotherapy of advanced breast cancer. [2016]Anthracyclines and taxanes are the two most active classes of chemotherapy for the treatment of advanced breast cancer. Recent studies have investigated combination therapy including doxorubicin (Dox) and paclitaxel. The efficacy of this combination has been established in a phase III study conducted by ECOG, comparing Dox/paclitaxel versus Dox versus paclitaxel. The combination is superior to Dox or paclitaxel with respect to response rate and time to disease progression, indicating that the combination provides a new standard for the first line treatment of metastatic breast cancer [1]. Phase II studies using higher doses of Dox and using shorter infusions of paclitaxel have suggested the combination can be further optimized; Gianni reported a 94% objective response rate using Dox 60 mg/m2 followed by paclitaxel 175 mg/m2 given over three hours [2]. The more active regimens are associated with enhanced cardiotoxicity; this toxicity can be avoided, however, by limiting the exposure to doxorubicin. The newer regimens have now been moved into phase III studies. Future progress for this disease will depend on the introduction of new agents. Two novel drugs are currently being investigated in randomised phase III trials as potentiators of Dox and/or paclitaxel. One is a monoclonal antibody from Genentech (Herceptin, trastuzumab) directed at the HER-2/neu oncogene, which is overexpressed in > 25% of breast cancers [3]. Recent results indicate that Herceptin in combination with paclitaxel (or with a Dox plus cyclophosphamide regimen) induces a higher response rate (RR) and prolongs the time to disease progression when compared to chemotherapy alone. The second agent N,N-diethyl-2[4-(phenylmethyl)-phenoxy] ethanamine.HCl (DPPE, BMS-217380-01), when combined with Dox, was associated with a higher RR than previously observed with Dox alone [4]. A randomized trial of Dox versus Dox plus DPPE is ongoing. The possible mechanisms underlying chemo-potentiation by these agents are discussed. As new anthracycline/taxane combinations establish themselves in earlier stages of the disease, the need for effective, non-cross resistant salvage regimens will emerge.
Docetaxel in the treatment of breast cancer: an update on recent studies. [2019]Recently there has been great interest in developing combination regimens involving taxanes and anthracyclines for the treatment of advanced breast cancer. Docetaxel in particular has substantial activity when combined with doxorubicin. In one randomized trial, the combination of doxorubicin 50 mg/m(2) and docetaxel 75 mg/m(2) showed significantly greater activity than doxorubicin plus cyclophosphamide (AC), producing a higher response rate (60% v 47%) and longer time to progression. In a second study, 484 patients were randomized to receive either docetaxel plus doxorubicin and cyclophosphamide (TAC) or 5-florouracil plus doxorubicin and cyclophosphamide. The response rate was significantly higher in the TAC arm (54% v 42%), including patients with unfavorable prognostic factors. Febrile neutropenia occurred more frequently in patients receiving TAC, but the incidence of infection and septic death was low and no greater than in the 5-florouracil/doxorubicin/cyclophosphamide arm. TAC was not associated with an increased risk of cardiotoxicity. Data on time to progression and survival are not yet available. The TAC and doxorubicin/docetaxel regimens have been compared with non-docetaxel-containing programs in randomized adjuvant trials which have completed accrual but are not yet mature. A second generation of adjuvant trials compares sequential versus synchronous docetaxel-based polychemotherapy. In addition, based on preclinical data suggesting a synergistic interaction between docetaxel, platinum salts, and trastuzumab, as well as preliminary data from pilot studies in patients with HER2-positive metastatic disease showing tolerability and activity, adjuvant studies of this novel three-agent combination are in progress in patients with HER2-positive early breast cancer.
Long-survival in responding patients with metastatic breast cancer treated with doxorubicin-docetaxel combination. A multicentre phase II trial. [2018]The doxorubicin-docetaxel combination is active in breast cancer; the aim of the present study was to evaluate the complete response rate and safety profile of the doxorubicin and docetaxel regimen as first-line chemotherapy in metastatic breast cancer patients.
Docetaxel/doxorubicin/cyclophosphamide in the treatment of metastatic breast cancer. [2018]A pilot phase II study examined the feasibility of 75 mg/m2 of docetaxel (Taxotere) in combination with 50 mg/m2 of doxorubicin and 500 mg/m2 of cyclophosphamide (Cytoxan, Neosar) in the first-line treatment of metastatic breast cancer. This study was designed to evaluate the efficacy and toxicity of the docetaxel/doxorubicin/cyclophosphamide combination both alone and as induction before high-dose chemotherapy, supplemented by autologous peripheral blood stem-cell transplantation. Patients were divided into three groups: one group received 8 courses of docetaxel/doxorubicin/cyclophosphamide; the second received 4 to 6 courses of the same combination with cell sampling, followed by high-dose chemotherapy with autologous peripheral blood stem-cell transplantation; and the third group's regimen was identical to that of the second, with additional granulocyte-colony stimulating factor (G-CSF, filgrastim [Neupogen]). Of 28 patients (149 courses) evaluable for toxicity and response, the overall response rate was 82%, with 5 (18%) complete responses and 18 (64%) partial responses. The most frequent hematologic toxicity was neutropenia; grade 4 neutropenia occurred in 86% of patients, with febrile neutropenia in 9 patients (18%). There was no incidence of infection, possibly because of the administration of oral ciprofloxacin (Cipro) from days 5 to 15 of each cycle. Nonhematologic adverse events were not severe; there was no significant cardiotoxicity. Future randomized trials of docetaxel/doxorubicin/cyclophosphamide as first-line adjuvant therapy of high-risk patients and as induction chemotherapy are in development.
Phase I trial of pegylated liposomal doxorubicin and docetaxel in advanced breast cancer. [2018]To develop a combination of pegylated liposomal doxorubicin (Doxil; Alza Pharmaceuticals, Palo Alto, CA) and docetaxel (Taxotere; Aventis Pharmaceutical, Parsipanny, NJ) that can be safely used for the treatment of advanced breast cancer.
Docetaxel and anthracycline polychemotherapy in the treatment of breast cancer. [2018]Given the single-agent activity of docetaxel and doxorubicin in metastatic breast cancer and their potential non-cross-resistance, several phase I/II pilot studies of either docetaxel/doxorubicin (TA) or TA plus cyclophosphamide (TAC) were conducted. The results of these studies show that the main toxicity is related to neutropenia and its consequences, although documented infections are rarely reported. Other toxicities are mild, while docetaxel-specific toxicities (fluid retention, nail changes, etc) are seldom seen. No significant cardiotoxicity, even when patients are exposed to a cumulative doxorubicin dose greater than 360 mg/m2, has been observed. In terms of efficacy, response rates in the range of 70% to 80% were noted in all studies, even for patients with visceral metastases. Preliminary data suggest that the combination of docetaxel with epirubicin is also feasible, with manageable toxicities and significant activity. Several phase III randomized trials using TA or TAC are presently being performed in first-line metastatic breast cancer and, most importantly, in the adjuvant setting to assess whether TA-based combinations will change the natural history of breast cancer.
Doxorubicin and taxane combination regimens for metastatic breast cancer: focus on cardiac effects. [2018]Investigation of the combination of the taxanes with doxorubicin in the treatment of breast cancer has logically progressed, with the ultimate goal of identifying a safe and effective regimen for use in the adjuvant setting. Initial phase II findings of the concurrent doxorubicin/paclitaxel combination resulted in substantial response rates, but at a high cost. A much higher percentage of patients than expected developed anthracycline-induced cardiomyopathy. Subsequent phase II and phase III trials have determined administration schedules of doxorubicin/paclitaxel that reduce the risk for cardiotoxicity. However, the overall response rate is only modestly improved over sequential single-agent therapy or standard doxorubicin-containing combination therapy. The lack of cardiotoxicity with docetaxel, its high antitumor activity, and its linear pharmacokinetics have made it an attractive taxane for combination with doxorubicin. In addition, it is easily administered in the outpatient setting. Phase I/II trials of the combination of doxorubicin/docetaxel resulted in high response rates with a lack of adverse modification of anthracycline-induced cardiomyopathy. These findings have been confirmed in a large phase III randomized trial where overall response rates and time to disease progression were significantly improved, but the incidence of cardiomyopathy was not different for the doxorubicin/docetaxel versus doxorubicin/cyclophosphamide (AC) regimen. Ongoing studies are underway to assess the role of the doxorubicin/docetaxel combination in the adjuvant setting as primary chemotherapy in the neoadjuvant setting. It is here that the most benefit on survival of breast cancer patients is likely to be shown. At the same time, it is in the adjuvant setting where the absence of potentially late cardiac and other toxicities must be assured.
Combining new agents with anthracyclines in metastatic breast cancer: an overview of recent findings. [2018]Historically, doxorubicin has been the most effective single agent in metastatic breast cancer, and the combination of doxorubicin with other active agents (as in the 5-fluorouracil/doxorubicin/cyclophosphamide protocol) has improved patient outcome. Results from phase II and several recent phase III studies provide evidence that new agents are also highly active in the treatment of metastatic breast cancer and suggest that they would be active in combination regimens with the anthracyclines. In particular, docetaxel (Taxotere; Rhône-Poulenc Rorer, Antony, France) has achieved a significantly higher response rate than doxorubicin in phase III randomized clinical trials. Studies to date indicate that this high response rate is achieved without accompanying cardiotoxicity. Several other new agents, notably, paclitaxel, vinorelbine, and gemcitabine, also have been evaluated in combination with the anthracyclines.
Docetaxel (Taxotere) in combination with anthracyclines in the treatment of breast cancer. [2018]Considering the single-agent activity of docetaxel (Taxotere; Rhône-Poulenc Rorer, Antony, France) and doxorubicin in breast cancer and their potential non-cross-resistance, several docetaxel/anthracycline-based combination chemotherapies were developed in phase I and II programs for metastatic breast cancer patients. The rationale for these combinations was also reinforced by the fact that docetaxel showed significant activity in phase III trials in patients previously exposed or having failed anthracycline chemotherapy. In a pivotal randomized phase III study of doxorubicin plus docetaxel versus doxorubicin plus cyclophosphamide as first-line chemotherapy for 429 patients with metastatic breast cancer, doxorubicin/docetaxel emerged as the more effective regimen. Despite a lower-dose intensity of doxorubicin, patients receiving doxorubicin/docetaxel experienced a higher response rate as well as a significantly longer time to progression and time to treatment failure. This difference was seen even in patients with poor-prognosis disease. Febrile neutropenia was more common in doxorubicin/docetaxel-treated patients. However, there were no septic deaths among 213 patients receiving doxorubicin/ docetaxel. Extrahematologic toxicity appeared mild for both regimens and the combination docetaxel/doxorubicin did not increase the cardiac toxicity expected for an anthracycline-containing regimen. Docetaxel plus doxorubicin is the first regimen, involving a newly developed agent, proven superior to a standard anthracycline-containing combination in metastatic breast cancer and its potential is now being investigated in the adjuvant setting.