Pembrolizumab + Carboplatin for Recurrent Gynecologic Cancer
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Female
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: University of Washington
Must not be taking: Steroids, Immunosuppressants
Disqualifiers: Immunodeficiency, Active infection, Autoimmune, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This phase II trial investigates how well pembrolizumab and carboplatin work in treating patients with ovarian, fallopian tube, or primary peritoneal cancer that has come back (recurrent). Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving pembrolizumab together with carboplatin may work better in treating patients with recurrent ovarian, fallopian tube, or primary peritoneal cancer.
Will I have to stop taking my current medications?
The trial protocol does not specify if you need to stop taking your current medications. However, if you are on systemic steroid therapy or any form of immunosuppressive therapy, you may need to stop or adjust it before starting the trial. It's best to discuss your specific medications with the trial team.
What data supports the effectiveness of the drug Pembrolizumab + Carboplatin for recurrent gynecologic cancer?
Research shows that pembrolizumab combined with carboplatin has been effective in treating recurrent ovarian cancer, and pembrolizumab alone is approved for advanced endometrial cancer. Additionally, pembrolizumab with chemotherapy is a standard treatment for advanced lung cancer, suggesting potential benefits in similar cancer types.
12345Is the combination of Pembrolizumab and Carboplatin safe for treating recurrent gynecologic cancer?
Carboplatin, a key drug in treating gynecologic cancers, is generally well-tolerated but can cause hypersensitivity reactions (allergic reactions) in some patients, especially after multiple doses. These reactions can often be managed by slowing the infusion rate and using anti-allergy medications. Pembrolizumab, another drug in this combination, is not specifically mentioned in the provided research, so its safety profile in this context is not detailed here.
678910How is the drug combination of Pembrolizumab and Carboplatin unique for treating recurrent gynecologic cancer?
This drug combination is unique because Pembrolizumab, an immunotherapy drug, works by helping the immune system recognize and attack cancer cells, while Carboplatin, a chemotherapy drug, enhances this effect by promoting T-cell activity. This combination is particularly promising for cancers that are resistant to platinum-based treatments, offering a novel approach compared to traditional therapies.
123411Eligibility Criteria
This trial is for patients with recurrent ovarian, fallopian tube, or primary peritoneal cancer who've had platinum-based chemo. They must have a certain level of CA-125 antigen and no measurable disease by specific criteria. Participants need to be sexually active individuals agreeing to contraception, have a life expectancy over 3 months, good performance status (0 or 1), and meet blood count and organ function requirements.Inclusion Criteria
Total bilirubin =< 1.5 X ULN OR direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 X ULN (performed within 14 days of treatment initiation)
My blood clotting time is normal or managed with medication.
I have ovarian, fallopian tube, or peritoneal cancer and have had chemotherapy including platinum-based treatment.
+14 more
Exclusion Criteria
I haven't had cancer treatment in the last 2 weeks or have recovered from its side effects.
I have stable brain metastases, not on steroids for 14 days, and no carcinomatous meningitis.
I have not received a live vaccine within the last 30 days.
+18 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Patients receive carboplatin IV on day -2 of cycle 1 and pembrolizumab IV on day 1 of each cycle. Cycles repeat every 6 weeks for up to 2 years.
Up to 2 years
Every 6 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment completion, with follow-ups at 30 days, then every 3 months for year 1, and every 6 months for year 2.
2 years
1 visit at 30 days, then every 3 months for year 1, every 6 months for year 2
Participant Groups
The trial tests pembrolizumab (an immunotherapy drug) combined with carboplatin (a chemotherapy drug) on patients whose cancer has returned. Pembrolizumab may boost the immune system's attack on cancer cells while carboplatin aims to stop tumor growth by killing cells or preventing their division.
1Treatment groups
Experimental Treatment
Group I: Treatment (carboplatin, pembrolizumab)Experimental Treatment5 Interventions
Patients receive carboplatin IV over 30 minutes on day -2 of cycle 1 only. Patients also receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 6 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo CT or MRI throughout the trial. Patients also undergo blood sample collection on the trial.
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:
Fred Hutch/University of Washington Cancer ConsortiumSeattle, WA
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Who Is Running the Clinical Trial?
University of WashingtonLead Sponsor
United States Department of DefenseCollaborator
National Cancer Institute (NCI)Collaborator
References
Pembrolizumab with low-dose carboplatin for recurrent platinum-resistant ovarian, fallopian tube, and primary peritoneal cancer: survival and immune correlates. [2022]Anti-programmed death 1 (PD1)/programmed cell death ligand 1 (PD-L1) therapies have shown modest activity as monotherapy in recurrent ovarian cancer. Platinum chemotherapies induce T-cell proliferation and enhance tumor recognition. We assessed activity and safety of pembrolizumab with carboplatin in recurrent platinum-resistant ovarian cancer.
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.
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.
Pembrolizumab plus pemetrexed-carboplatin combination in first-line treatment of advanced non-squamous non-small cell lung cancer: a multicenter real-life study (CAP29). [2023]Pembrolizumab combined with chemotherapy is now first-line standard of care in advanced non-small cell lung cancer. This real-life study aimed to assess efficacy and safety of carboplatin-pemetrexed plus pembrolizumab in advanced non-squamous non-small cell lung cancer.
Clinical and Biological Activity of Chemoimmunotherapy in Advanced Endometrial Adenocarcinoma: A Phase II Trial of the Big Ten Cancer Research Consortium. [2023]The objective of this study was to assess the efficacy and safety of pembrolizumab in combination with standard carboplatin/paclitaxel in patients with advanced endometrial cancer (EC).
Incidence of Carboplatin-related hypersensitivity reactions in Japanese patients with gynecologic malignancies. [2018]Carboplatin is one of the most commonly used and well-tolerated agents for gynecologic malignancies. The rate of hypersensitivity reactions (HSRs) in the overall population of patients receiving carboplatin has been reported to increase after multiple doses of the agent. We retrospectively analyzed the incidence, clinical features, management, or outcome of carboplatin-related HSRs in 113 Japanese patients with gynecologic malignancies and the possibility of rechallenge with the drug. We intravenously administered carboplatin after paclitaxel or docetaxel. Mild HSRs are resolved by temporary interruption of carboplatin infusion, an additional antihistamine, and/or a corticosteroid. If HSRs arose, carboplatin was diluted, not exceeding 1 mg/mL, and slowly infused over 2 hours in subsequent cycles. Ten patients experienced carboplatin HSRs, with an overall incidence of 8.85%. The first HSR episode was mild in all cases. When retreated with carboplatin, 4 exhibited severe HSRs. More than 9 cycles and/or more than 5000 mg of carboplatin administration significantly increased the incidence of HSRs. In particular, carboplatin treatment beyond 15 cycles and/or 8000 mg increased the risk of severe HSRs (P
Combination therapy with gemcitabine and carboplatin in recurrent ovarian cancer. [2022]Many patients with advanced ovarian cancer will develop recurrent disease. For those patients who have recurrence of disease at least 6 months after initial therapy, the paclitaxel-platinum combination has been shown to be a superior treatment to platinum monotherapy. However, many patients develop clinically relevant neurotoxicity, frequently resulting in treatment discontinuation. The efficacy and safety of an alternative regimen that does not show significant neurotoxicity were evaluated by comparing gemcitabine-carboplatin with carboplatin in platinum-sensitive recurrent ovarian cancer patients in a Gynecologic Cancer InterGroup trial of the Arbeitsgemeinschaft Gynakologische Onkologie Ovarian Cancer Study Group, the National Cancer Institute of Canada Clinical Trials Group, and the European Organisation for Research and Treatment of Cancer Gynaecological Cancer Group. Participants with recurrent platinum-sensitive ovarian cancer were randomly assigned to receive either gemcitabine-carboplatin or carboplatin every 21 days. The primary objective was to compare progression-free survival (PFS) between the groups. From September 1999 to April 2002, 356 patients (178 participants received gemcitabine-carboplatin, 178 received carboplatin only) were randomized to treatment. Patients received six cycles of either gemcitabine-carboplatin or carboplatin. With a median follow-up of 17 months, median PFS was 8.6 months for gemcitabine-carboplatin (95% confidence interval [CI] 7.9-9.7 months) and 5.8 months for carboplatin (95% CI 5.2-7.1 months; hazard ratio [HR] 0.72 [95% CI 0.58-0.90; P = 0.0032]). The response rate for the gemcitabine-carboplatin group was 47.2% (95% CI 39.9-54.5%) and 30.9% for carboplatin group (95% CI 24.1-37.7%; P = 0.0016). The HR for overall survival was 0.96 (95% CI 0.75-1.23; P = 0.7349). Patients treated with gemcitabine-carboplatin reported significantly faster palliation of abdominal symptoms and a significantly improved global quality of life. Gemcitabine-carboplatin treatment significantly improves the PFS of patients with platinum-sensitive recurrent ovarian cancer.
Clinical pharmacology of carboplatin. [2013]Experimental and clinical data indicate that carboplatin is as effective as cisplatin in the treatment of ovarian cancer patients with advanced bulky disease. It has an improved toxicity profile with a low incidence of ototoxicity, neuropathy, and nephropathy. In the absence of severe myelosuppression, the dose of carboplatin should be escalated in patients who have good renal function. Over the next few years, carboplatin will either replace cisplatin, or will be easier to use in a dose-intensive fashion.
Risk Factors of Hypersensitivity to Carboplatin in Patients with Gynecologic Malignancies. [2020]We evaluated the prevalence of and risk factors for hypersensitivity reactions related to carboplatin, which is commonly used to treat gynecological malignancies. All women with pathologically documented ovarian, fallopian tube, or primary peritoneal cancer treated with carboplatin alone or a carboplatin-based combination chemotherapy regimen at a single hospital between January 2006 and December 2013 were retrospectively recruited. We analyzed the incidence, characteristics, risk factors, management, and outcomes of carboplatin-related hypersensitivity reactions among these patients. Among 735 eligible women, 75 (10.2%) experienced a total of 215 carboplatin-related hypersensitivity reaction events. The annual incidence of carboplatin-related hypersensitivity reactions gradually increased from 0.88% in 2006 to 5.42% in 2013. The incidence of carboplatin-related hypersensitivity was higher in patients with advanced stage disease (P < 0.001, Kruskal-Wallis test), serous and mixed histological types (P = 0.003, Kruskal-Wallis test), malignant ascites (P = 0.009, chi-square test), and history of other drug allergy (P < 0.001, chi-square test). Compared to women without hypersensitivity reactions, women who experienced hypersensitivity reactions had a significantly greater median cycle number (12 vs. 6, P < 0.001, independent sample t-test) and dose (6,816 vs. 3,844 mg, P < 0.001, independent sample t-test). The cumulative incidence of carboplatin-related hypersensitivity reactions dramatically increased with >8 cycles or dose >3,500 mg. Therefore, disease severity, histological type, malignant ascites, past drug allergies, and cumulative carboplatin dose are risk factors for carboplatin-related hypersensitivity reactions. Such reactions could potentially be reduced or prevented by slowing the infusion rate and using a desensitization protocol involving anti-allergy medications.
Efficacy and Adverse Events of Carboplatin Desensitisation Therapy for Gynaecological Cancer: A Retrospective Study. [2022]Carboplatin, the key drug used in treating gynaecological cancer, has an approximately 12-16% risk of hypersensitivity reactions. We aimed to investigate the efficacy and adverse effects of carboplatin desensitisation therapy for gynaecological cancer.
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.