Drug Combination Therapy for Breast Cancer
(NeoADAPT Trial)
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Female
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Must not be taking: Paclitaxel, Carboplatin, Checkpoint inhibitors
Disqualifiers: Metastatic disease, Inflammatory breast cancer, others
Stay on Your Current Meds
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?Eligible patients with stage 2 and 3 triple negative breast cancer will be treated with 4 cycles of neoadjuvant paclitaxel/carboplatin/pembrolizumab. A PET scan will be performed at baseline and after 1 cycle of therapy. A breast MRI will be performed after treatment completion. Patients with complete clinical response will proceed to surgery. Patients with clinical residual disease will complete neoadjuvant rescue with 4 cycles of doxorubicin/cyclophosphamide prior to surgery. If residual disease identified after surgery, adjuvant therapy to be determined by the treating oncologist (may include doxorubicin/cyclophosphamide/pembrolizumab, capecitabine etc).
Will I have to stop taking my current medications?
The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.
What data supports the effectiveness of the drug combination therapy for breast cancer?
Research shows that the combination of paclitaxel and carboplatin is effective in treating advanced breast cancer, with response rates of 40-60% and manageable side effects. Additionally, pembrolizumab combined with carboplatin has shown promise in BRCA-related metastatic breast cancer.
12345Is the drug combination therapy generally safe for humans?
Pembrolizumab (Keytruda), part of the drug combination, has been associated with some side effects, including pneumonitis (lung inflammation) in 1%-5% of patients and a rare risk of type 1 diabetes in 0.2% of cases. These side effects have been observed in treatments for various cancers.
678910What makes the drug combination therapy of Carboplatin, Paclitaxel, and Pembrolizumab unique for breast cancer?
This drug combination is unique because it combines Carboplatin and Paclitaxel, which are known to be effective in breast cancer, with Pembrolizumab, an immunotherapy that may enhance the body's immune response against cancer cells, particularly in BRCA-related metastatic breast cancer.
2451112Eligibility Criteria
This trial is for individuals with stage 2 or 3 triple negative breast cancer. Participants will undergo specific chemotherapy and immunotherapy treatments, followed by imaging tests like PET scans and MRI to monitor response. Those showing complete clinical response go straight to surgery; others receive additional chemo before surgery.Inclusion Criteria
I am 18 years old or older.
I can take care of myself and am up and about more than half of my waking hours.
My doctor agrees I can handle chemo-immunotherapy without major health risks.
+2 more
Exclusion Criteria
My cancer has spread or returned in the chest area.
I have been diagnosed with inflammatory breast cancer.
Patients unable to undergo PET or MRI
+1 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
1 visit (in-person)
Neoadjuvant Treatment
Participants receive 4 cycles of paclitaxel, carboplatin, and pembrolizumab. PET scan at baseline and after 1 cycle, MRI after treatment completion.
12 weeks
4 visits (in-person)
Surgery
Patients with clinical complete response proceed to surgery. Patients with residual disease may receive additional neoadjuvant therapy before surgery.
4 weeks
1 visit (in-person)
Adjuvant Therapy
Patients with pathologic complete response may receive pembrolizumab. Patients with residual disease may receive additional adjuvant therapy.
16 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment
3 years
Participant Groups
The study tests a combination of neoadjuvant therapies (paclitaxel, carboplatin, pembrolizumab) in patients with TNBC, using PET scans for early treatment adaptation. It explores whether changing therapy based on PET scan results can improve outcomes before surgery.
1Treatment groups
Experimental Treatment
Group I: Neoadjuvant therapyExperimental Treatment7 Interventions
4 cycles of paclitaxel/carboplatin/pembrolizumab
Carboplatin is already approved in United States, European Union, Canada for the following indications:
🇺🇸 Approved in United States as Paraplatin for:
- Ovarian cancer
- Testicular cancer
- Lung cancer
- Head and neck cancer
- Brain cancer
🇪🇺 Approved in European Union as Carboplatin for:
- Ovarian cancer
- Small cell lung cancer
🇨🇦 Approved in Canada as Carboplatin for:
- Ovarian cancer
- Small cell lung cancer
- Testicular cancer
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsBaltimore, MD
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Who Is Running the Clinical Trial?
Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsLead Sponsor
Breast Cancer Research FoundationCollaborator
References
Paclitaxel-carboplatin combination chemotherapy in advanced breast cancer: accumulating evidence for synergy, efficacy, and safety. [2018]Patients with metastatic breast cancer receive multiple lines of cytotoxic chemotherapy, with taxane and anthracycline-based regimens being the most active. Anthracyclines carry the risk of significant cardiotoxicity at high cumulative doses and when combined with trastuzumab, an anti-HER2 antibody. Carboplatin has shown promising single-agent activity in advanced breast cancer, is not a P-glycoprotein substrate, and is conveniently administered on an outpatient basis. Preclinical experiments demonstrated schedule-dependent synergistic cytotoxic effects of the paclitaxel first/carboplatin last (PC) combination. Pharmacokinetic parameters of paclitaxel and carboplatin were studied by Hellenic Cooperative Oncology Group (HECOG) and no significant interaction or correlation with clinical parameters were found. We assessed PC both as salvage as well as first-line treatment of advanced breast cancer patients in phase II studies which disclosed 40-60% response rates and median survival times of 12-20 mo with manageable toxicity. These results were confirmed by other groups and prompted us to the first randomized phase III trial comparing PC to the standard of epirubicin/paclitaxel (EP), a trial that showed equivalent efficacy and tolerable toxicity for PC. Registry retrospective analysis identified factors prognostic for improved outcome: good performance status, low tumor burden, lack of anthracycline exposure and of hormonal maintenance therapy. PC combinations with HER1 or HER2 modulators are being evaluated both by HECOG and by international groups. Paclitaxel coupled with carboplatin provides an alternative therapeutic option for anthracycline-exposed patients and warrants further clinical research in the direction of anthracycline-free management of metastatic breast cancer.
Paclitaxel and carboplatin for advanced breast cancer. [2015]This report evaluates the activity of paclitaxel alone (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), carboplatin alone, and their combination in the treatment of patients with advanced breast cancer. The preliminary safety information of this combination in other tumor types also is discussed. Finally, the overall rationale for ongoing study of the efficacy of paclitaxel and carboplatin, along with appropriate translational studies, as first-line chemotherapy in patients with metastatic breast cancer is examined. Both paclitaxel and carboplatin have well-established single-agent activity in the treatment of women with breast cancer. The tolerability of this combination, using the sequence paclitaxel followed by carboplatin infusion, already has been established in patients with lung cancer and ovarian cancer. In addition, this therapy has the novel attribute of a relative platelet-sparing effect. A phase II trial evaluating the efficacy of the paclitaxel/carboplatin combination, along with an evaluation of thrombopoietin levels and quality of life, has been initiated recently through the North Central Cancer Treatment Group. In this trial, intravenous paclitaxel 200 mg/m2 infused over 3 hours is followed by carboplatin at a calculated area under the concentration-time curve dose of 6, with cycles repeated every 21 days. Results from this trial will help document the role of the paclitaxel/carboplatin combination in the treatment of women with breast cancer.
Frequent pathologic complete responses in aggressive stages II to III breast cancers with every-4-week carboplatin and weekly paclitaxel with or without trastuzumab: a Brown University Oncology Group Study. [2022]To evaluate the efficacy and safety of neoadjuvant carboplatin and weekly paclitaxel +/- weekly trastuzumab in resectable and locally advanced breast cancer.
Combined doxorubicin and paclitaxel in advanced breast cancer: effective and cardiotoxic. [2020]Paclitaxel has shown activity in metastatic breast cancer, including anthracycline-resistant breast cancer. The efficacy, toxicity and optimal scheduling of the combination of the two drugs needs to be defined.
A phase II study of pembrolizumab plus carboplatin in BRCA-related metastatic breast cancer (PEMBRACA). [2023]BRCA1/2-related metastatic breast cancers (mBC) are sensitive to DNA-damage agents and show high tumor-infiltrated lymphocytes. We hypothesized that the association between pembrolizumab and carboplatin could be active in BRCA-related mBC.
Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]Pembrolizumab (Keytruda) is a monoclonal antibody against the programmed cell death-1 (PD-1) receptor on lymphocytes, which is one of the immune checkpoint inhibitors (ICIs) approved for multiple solid and hematologic malignancies. Although ICIs have proven to be more effective and less toxic compared to chemotherapy, there are reports of adverse side effects with ICIs. For example, pneumonitis is a potentially lethal side effect occurring in 1%-5% of patients who received ICIs in clinical trials, and there are case reports with clinical and radiological features of checkpoint inhibitor-pneumonitis (CIP).
Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. [2022]Pembrolizumab (Keytruda; Merck Sharp & Dohme) is a humanized IgG4 monoclonal antibody used in cancer immunotherapy. It targets the programmed cell death-1 (PD-1) receptor, which is important in maintaining self-tolerance. However, immune checkpoint blockade is associated with a risk for immune-related adverse events (irAEs) potentially affecting the endocrine organs. Type 1 diabetes mellitus is a rare irAE of PD-1 inhibitors, occurring in 0.2% of cases.
New Approved Use for Keytruda. [2022]Pembrolizumab (Keytruda) is now approved as a single agent to treat advanced endometrial carcinoma that is microsatellite instability-high or mismatch repair deficient in those whose disease has progressed following prior systemic therapy in any setting and who are not candidates for curative surgery or radiation.
Pembrolizumab Approved for Esophageal or Gastroesophageal Cancer. [2023]Pembrolizumab (Keytruda) has been approved to treat metastatic or locally advanced esophageal or gastroesophageal junction cancer. It is used in combination with platinum- and fluoropyrimidine-based chemotherapy.
Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]A phase II trial investigating the therapeutic effect of neoadjuvant programmed cell death 1 (PD-1) inhibitor pembrolizumab (MK-3475, KEYTRUDA®) administered prior to surgery for the treatment of non-small cell lung cancer (NSCLC) has been conducted (NCT03197467). We report the first clinical results of a planned interim safety analysis after 15 patients were enrolled.
Paclitaxel and doxorubicin in metastatic breast cancer. [2015]For the past decades the anthracyclines have been regarded as among the most active drugs for the treatment of metastatic breast cancer. However, the 5-year survival rate in patients with stage IV breast cancer continues to be below 20%, and new active drugs and drug combinations clearly must be explored. Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has been demonstrated to be highly effective in treating patients with advanced breast cancer, including those with anthracycline-resistant breast cancer, a fact that has led to efforts to combine paclitaxel and anthracyclines. Several studies aiming to define the optimal dose and schedule of combination paclitaxel/doxorubicin have now been completed or are ongoing. Phase I/II studies have yielded encouraging preliminary response rates but quite variable toxicity profiles depending on the schedule used. These clinical trials involving combination paclitaxel/doxorubicin are reviewed, with special emphasis on the short-infusion trials.
Paclitaxel-containing combination chemotherapy for metastatic breast cancer. [2018]After demonstration of the marked antitumor activity against metastatic breast cancer of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), other clinical trials explored the possibility of combining this new active agent with other cytotoxic drugs with proven efficacy against breast carcinoma. Paclitaxel plus doxorubicin, thought to be the most effective single agents against breast cancer, yielded remission rates ranging from 60% to 80%, including some complete remissions. Schedule-dependent toxic interactions were observed when paclitaxel preceded the administration of doxorubicin. Paclitaxel by 3-hour infusion plus doxorubicin by bolus proved to be a highly tolerable regimen, with overall remission rates in excess of 90% and complete remission rates approaching 50%. A paclitaxel plus cisplatin combination has been studied at numerous schedules and doses with variable activity and tolerability, although one group in Vancouver, Canada, reported an 85% overall response rate with the combination administered on a 14-day schedule in previously treated patients, most of whom had received doxorubicin. Paclitaxel also has been combined with cyclophosphamide, mitoxantrone, edatrexate, 5-fluorouracil, and other agents for the treatment of breast cancer. Of interest are recent reports on paclitaxel and vinorelbine, showing this combination to be clearly active, with good tolerability and rapid recovery after myelosuppression. Trials of this combination are ongoing with granulocyte colony-stimulating factor support, on an every-14-day schedule. The doxorubicin/paclitaxel doublet remains the most promising in terms of activity, although other combinations with a high degree of activity and good tolerance are being sought.