Carboplatin +/- Tocilizumab for Breast Cancer
Recruiting in Palo Alto (17 mi)
+3 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Kathy Miller
Must not be taking: Methotrexate, Corticosteroids, PARP inhibitors
Disqualifiers: Active infection, HER2+ disease, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Approved in 3 Jurisdictions
Trial Summary
What is the purpose of this trial?This is a randomized Phase II study of standard of care (SOC) chemotherapy monotherapy vs. SOC chemotherapy combined with tocilizumab in in Black and non-Black patients with metastatic triple negative or ER low breast cancer.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications, but you cannot use methotrexate or certain corticosteroids. Hormone therapy must be stopped at least 2 weeks before joining the trial.
What data supports the effectiveness of the drug Carboplatin in treating breast cancer?
Research shows that Carboplatin, when used in combination with other drugs like paclitaxel, has shown promising results in treating advanced breast cancer, with response rates of 40-60% and manageable side effects. Additionally, Carboplatin has been effective in increasing complete response rates in aggressive breast cancers, especially in patients with certain genetic mutations.
12345Is the combination of Carboplatin and Tocilizumab safe for humans?
Carboplatin is generally well-tolerated in humans, with mild side effects like nausea and low blood cell counts. Tocilizumab, used for other conditions, is also considered safe but can cause side effects like infections and liver enzyme changes. While specific safety data for the combination of Carboplatin and Tocilizumab in breast cancer is limited, both drugs have been used safely in humans for other conditions.
13678What makes the drug combination of Carboplatin and Tocilizumab unique for breast cancer treatment?
The combination of Carboplatin and Tocilizumab is unique because it pairs a chemotherapy drug (Carboplatin) with an immunotherapy drug (Tocilizumab), which is typically used to treat inflammation in conditions like rheumatoid arthritis. This novel approach aims to enhance the immune response against breast cancer, potentially offering a new treatment option for patients.
123910Eligibility Criteria
This trial is for adults with metastatic triple negative or ER-low breast cancer who have completed prior therapy at least a year ago. They must be in good physical condition, have adequate organ function, and not be pregnant. Participants need to consent to biopsies and agree to use effective contraception. Those with treated brain metastases may join if stable.Inclusion Criteria
I am 18 years old or older.
I agree to a biopsy for this study.
Ability to provide written informed consent and HIPAA authorization
+9 more
Exclusion Criteria
My cancer is HER2 positive based on specific test results.
I have not started hormone therapy in the last 2 weeks.
I have active or symptomatic brain or spinal cord problems.
+6 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants are randomized to receive either SOC chemotherapy monotherapy or SOC chemotherapy combined with tocilizumab
up to 2 years
Follow-up
Participants are monitored for safety and effectiveness after treatment
4-8 weeks
Participant Groups
The study compares carboplatin alone versus carboplatin combined with tocilizumab in patients with certain types of advanced breast cancer. It's randomized, meaning participants are assigned to one of the two treatment groups by chance.
4Treatment groups
Experimental Treatment
Active Control
Group I: Non-Black Combination treatmentExperimental Treatment2 Interventions
Group II: Black Combination treatmentExperimental Treatment2 Interventions
Group III: Black MonotherapyActive Control1 Intervention
Group IV: Non-Black MonotherapyActive Control1 Intervention
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:
Roswell Park Comprehensive Cancer CenterBuffalo, NY
IU Health Joe and Shelly Schwarz Cancer CenterCarmel, IN
Indiana University Melvin and Bren Simon Comprehensive Cancer CenterIndianapolis, IN
Sidney and Lois Eskenazi HospitalIndianapolis, IN
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Who Is Running the Clinical Trial?
Kathy MillerLead Sponsor
Breast Cancer Research FoundationCollaborator
Susan G Koman for the Cure Breast Cancer FoundationCollaborator
Genentech, Inc.Industry Sponsor
References
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.
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.
Phase II study of carboplatin in advanced breast cancer: preliminary results. [2013]The antitumor activity of carboplatin (400 mg/m2 intravenously every 4 weeks) in advanced breast cancer was evaluated in two consecutive trials enrolling patients with and without prior exposure to chemotherapy, respectively. All patients had measurable disease in at least one site. The first trial included patients who had received prior chemotherapy (adjuvant, neoadjuvant, or chemotherapy for metastatic disease). All but one of these patients had previously received doxorubicin-containing combinations. There were no objective responses among the first 14 evaluable patients, although 7 of them had stable disease, including 2 with minor responses. The second trial, carried out with patients who had no prior exposure to chemotherapy, is ongoing. Currently, 6 of 19 evaluable patients have obtained a complete (1) or partial (5) response to carboplatin, resulting in an overall response rate of 32%. In both studies, toxicity was mild, mainly consisting of emesis (88%), leukopenia (22%), and thrombocytopenia (12%). Thus, by standard criteria, carboplatin was not found to be active in breast cancer patients with prior exposure to chemotherapy. Preliminary results in patients without such exposure are encouraging, although additional patients are needed to confirm these data.
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.
Assessing the role of platinum agents in aggressive breast cancers. [2022]As anticipated by their structure and mechanism of action, platinum analogs exhibit clinically significant antitumor activity in the more aggressive forms of breast cancer, both alone and in combination with other cytotoxic agents and targeted therapies. In early-stage human epidermal growth factor receptor-2 (HER2)-positive breast cancer, the administration of carboplatin together with a taxane (usually docetaxel) and trastuzumab (and pertuzumab in the neoadjuvant setting) is a standard of care regimen. In BRCA1 mutation carriers, neoadjuvant treatment with single-agent cisplatin results in a high pathologic complete response (pCR) rate. In both BRCA-mutated and sporadic triple-negative breast cancer, the addition of carboplatin to neoadjuvant chemotherapy significantly increases pCR rates. Despite these encouraging results, many questions remain about the role of platinum analogs in these patient populations, including their optimal doses and schedules, and utility in patients with advanced stage disease. A number of these questions are addressed by ongoing trials.
Atezolizumab plus carboplatin and nab-paclitaxel versus carboplatin and nab-paclitaxel as treatments for Chinese, treatment-naïve, stage IV, non-squamous, non-small-cell lung cancer patients: A retrospective analysis. [2022]The IMpower trials reported significant effects of atezolizumab-containing chemotherapies on Caucasian patients. Chinese patients differ from their Western counterparts in terms of driver mutations, etiologies, and regimen tolerance. In China, atezolizumab-containing chemotherapies are not cost-effective. Atezolizumab addition triggers grade >3 adverse events. Here, we evaluated the effectiveness and the safety profile of atezolizumab plus carboplatin and nab-paclitaxel compared to carboplatin and nab-paclitaxel in treatment-naïve Chinese patients with confirmed stage IV, non-squamous, non-small-cell lung cancer. All patients completed six cycles of 1200 mg of atezolizumab/3 weeks plus 6 mg/ml/min area-under-the-curve carboplatin/3 weeks plus 100 mg/m2 nab-paclitaxel/week (n = 115; ACN cohort) or 6 mg/ml/min area-under-the-curve carboplatin/3 weeks plus 100 mg/m2 nab-paclitaxel/week (n = 130; CNP cohort). The progression-free survival (12.98 ± 2.57 months vs. 10.89 ± 2.18 months, p < .0001) and overall survival (38.04 ± 19.8 months vs. 33.59 ± 87 months, p = .012) of patients in the ACN cohort were higher than those of patients in the CNP cohort after 48 weeks of follow-up. A total of 97 (84%) patients in the ACN cohort and 94 (72%) in the CNP cohort developed grade ≥3 adverse events (p = .030). A total of 84 (73%) patients from the ACN cohort and 107 (82%) from the CNP cohort died during 48 weeks of follow-up (p = .091). The addition of atezolizumab to carboplatin and nab-paclitaxel enhanced progression-free and overall survival but increased the risk of grade ≥3 adverse events in Chinese, treatment-naïve, stage IV, non-squamous, non-small-cell lung cancer patients who completed treatment (Level of Evidence: III; Technical Efficacy Stage: 4).
Carboplatin and nab-paclitaxel chemotherapy with or without atezolizumab as front-line management for treatment-naïve metastatic nonsquamous non-small cell lung cancer with PD-L1 staining: a retrospective study. [2023]The aim of this retrospective review was to compare the efficacy and safety of the atezolizumab plus carboplatin and nab-paclitaxel regimen versus the carboplatin and nab-paclitaxel regimen as front-line management for treatment-naïve, metastatic nonsquamous programmed death-ligand 1 (PD-L1)-positive non-small cell lung cancer (NSCLC) in a selected population.
Probable cutaneous hypersensitivity to carboplatin single-agent chemotherapy in a dog. [2013]Carboplatin is usually a well-tolerated drug and has many applications in veterinary oncology. The side effects of carboplatin described in the veterinary literature include myelotoxicity, nephrotoxicity, digestive and appetite disorders. In 114 dogs treated by single-agent chemotherapy with carboplatin, we observed a rate of non-haematological toxicities of 19·3% (personal observation). This case report describes the first case of cutaneous delayed-hypersensitivity to carboplatin in a dog, diagnosed according to the official ABON-system, which determines a causal association between a suspected product and a reported reaction (A=probable, B=possible, O=unclassifiable and N=unlikely), and an experimental intradermal skin test. Antihistamines were used to treat the reaction, and future carboplatin treatments were adjusted by premedication with corticosteroids, prolonged infusion and a reduction of 20% of the first dose of carboplatin. No further reactions were noted during the following treatments.
A phase II study of pemetrexed and carboplatin in patients with locally advanced or metastatic breast cancer. [2015]Pemetrexed and carboplatin have demonstrated activity in breast cancer. Their potential synergism in experimental models and the proven efficacy of pemetrexed/platinum in other indications make pemetrexed/carboplatin an attractive combination in breast cancer. Thus, this two-stage, sequential, open-label, multicenter, phase II study assessed the efficacy and safety of pemetrexed plus carboplatin as first-line therapy in patients with locally advanced breast cancer (LABC) or metastatic breast cancer (MBC).
Paclitaxel and carboplatin as first-line chemotherapy for advanced breast cancer. [2015]In a phase II study, 66 patients with advanced breast cancer (median age 56 years; range, 28 to 75 years) were treated with paclitaxel (Taxol), 175 mg/m2 infused over 3 hours, and carboplatin (Paraplatin), dosed to attain an area under the concentration-time curve (AUC) of 6 mg x min/mL; treatment was repeated every 3 weeks. A total of 38 (58%) patients had received prior adjuvant chemotherapy, 21 with a regimen containing an anthracycline or mitoxantrone (Novantrone). As of May 1997, 295 cycles of paclitaxel-carboplatin have been administered, 248 (84%) at full dose. The relative dose intensity of paclitaxel is 0.9 (range, 0.5 to 1.2). Of the 66 patients, 8 (12%) have achieved a complete response and 27 (41%) a partial response, for a total response rate of 53%. Grade 3 to 4 toxicities have included anemia (5%), leukopenia (25%), thrombocytopenia (5%), nausea/vomiting (7%), myalgias/arthralgias (4%), allergic reaction, neurotoxicity, and infection (2% each). Alopecia has been universal. Median time to progression is 8.9 months; median survival has not yet been reached. We conclude that the combination of paclitaxel and carboplatin has significant activity in advanced breast cancer and can easily be administered on an outpatient basis with manageable toxicity.