Trial Summary
What is the purpose of this trial?This trial is testing a new drug, CPI-0209, combined with chemotherapy in patients with recurrent ovarian cancer. The goal is to see if CPI-0209 can make chemotherapy work better and prevent the cancer from returning by blocking resistance and spread.
What data supports the idea that CPI-0209 + Carboplatin for Ovarian Cancer is an effective treatment?The available research shows that carboplatin, when used in combination with other drugs, has been effective in treating ovarian cancer. For example, in one study, carboplatin combined with other drugs showed response rates between 44% to 75% in patients with advanced ovarian cancer. Additionally, carboplatin has been found to have similar effectiveness to another drug, cisplatin, but with fewer side effects. However, there is no specific data provided on the combination of CPI-0209 with carboplatin for ovarian cancer in the available research.134913
Is the drug Carboplatin, used with CPI-0209, a promising treatment for ovarian cancer?Yes, Carboplatin is a promising drug for ovarian cancer. It has shown a good response rate, especially in patients who haven't had chemotherapy before. When combined with other drugs, it has been effective in reducing tumor markers significantly. It can be used safely in outpatient settings and has a manageable side effect profile.125611
What safety data exists for the treatment of CPI-0209 and Carboplatin in ovarian cancer?The safety data for Carboplatin, used in various studies, indicates that its primary toxicity is hematologic, particularly myelosuppression and thrombocytopenia. In a phase II study for ovarian cancer, severe thrombocytopenia was observed in one-third of patients at a 400 mg/m2 dose. Another study combining Carboplatin with cisplatin and G-CSF in ovarian cancer found the maximum tolerated dose to be AUC 7 mg/ml x min, with an 80% response rate. Intraperitoneal administration of Carboplatin also showed myelosuppression as the dose-limiting toxicity, with a recommended starting dose of 400 mg/m2 for pretreated patients. Overall, Carboplatin has a manageable safety profile, but careful dose management is necessary to minimize hematologic toxicity.2781012
Do I need to stop taking my current medications to join the trial?The trial protocol does not specify if you need to stop taking your current medications. However, you cannot take warfarin or other coumadin-derived anticoagulants, and you must stop using herbal supplements and certain foods like grapefruit 7 days before starting the study drug. It's best to discuss your current medications with the trial team.
Eligibility Criteria
This trial is for women with ovarian cancer that has returned more than 6 months after platinum-based chemotherapy. They must be able to take oral medication, have a life expectancy of at least 3 months, and agree to use effective contraception. Exclusions include certain medical conditions, recent treatments or surgeries, and those not recovered from previous therapy side effects.Inclusion Criteria
I had brain metastasis treated over 8 weeks ago, am off steroids for 4 weeks, and my condition is stable or improved.
I have been on the same birth control pill for at least 3 months.
I can care for myself and my doctor expects me to live at least 3 more months.
I can swallow pills or liquid medicine.
Exclusion Criteria
I haven't had major surgery in the last 2 weeks or still have major side effects from it.
I had radiotherapy recently and still experience side effects.
I have a history of HIV infection.
My cancer is considered to be of low aggressiveness.
I have severe nerve damage.
My liver disease is moderately to severely advanced.
I am currently taking warfarin or a similar blood thinner.
I do not have any severe health conditions that would make it unsafe for me to join the study.
I am currently being treated for an infection.
Treatment Details
The study tests CPI-0209 combined with Carboplatin followed by maintenance CPI-0209 in patients with recurrent ovarian cancer who responded well previously to platinum-based treatment. The goal is to see if this combination helps control the cancer better than current treatments.
3Treatment groups
Experimental Treatment
Group I: CPI-0209 (250 mg) + carboplatinExperimental Treatment2 Interventions
CPI-0209: 250 mg (oral dosing) carboplatin administered intravenously as per institutional standards
Group II: CPI-0209 (200 mg) + carboplatinExperimental Treatment2 Interventions
CPI-0209: 200 mg (oral dosing) carboplatin administered intravenously as per institutional standards
Group III: CPI-0209 (150 mg) + carboplatinExperimental Treatment2 Interventions
CPI-0209: 150 mg (oral dosing) carboplatin administered intravenously as per institutional standards
Carboplatin is already approved in United States, European Union, Canada for the following indications:
πΊπΈ Approved in United States as Paraplatin for:
- Ovarian cancer
- Testicular cancer
- Lung cancer
- Head and neck cancer
- Brain cancer
πͺπΊ Approved in European Union as Carboplatin for:
- Ovarian cancer
- Small cell lung cancer
π¨π¦ 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:
Magee-Womens Research Institute / UPMC Magee Womens HospitalPittsburgh, PA
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Who is running the clinical trial?
Lan CoffmanLead Sponsor
MorphoSys AGIndustry Sponsor
National Cancer Institute (NCI)Collaborator
References
[Role of carboplatin in treating patients with advanced ovarian cancer]. [2017]Results of Carboplatin treatment of ovarian cancer were presented. Drug resistance was observed during therapy of first course type. Objective response to treatment was observed with 5 patients from 27 ones (19%).
Intraperitoneal carboplatin: rationale and experience. [2018]We conducted a phase I/II trial of intraperitoneal (IP) carboplatin in 27 patients with advanced gynecologic malignancies. This was based on the known activity of carboplatin in ovarian cancer and pharmacologic measurements that predict a favorable ratio of IP to plasma drug exposure when carboplatin is administered by the IP route. All patients had extensive prior therapy with cisplatin (mean dose, 554 mg/m2). Starting dose was 200 mg/m2, which was escalated to 500 mg/m2. Patients with compromised renal function (creatinine clearance 30 to 60 mL/min) had slower escalations than patients with creatinine clearances greater than 60 mL/min. Myelosuppression, especially thrombocytopenia, was the dose-limiting toxicity. In pretreated patients, we recommend a starting dose of 400 mg/m2. Patients with creatinine clearances of 30 to 60 mL/min should start at the lower dose of 200 mg/m2. This is in general agreement with the results of other trials of IP carboplatin. Measurements of IP carboplatin in preclinical studies predict less tissue penetration by carboplatin than the parent compound cisplatin. Nevertheless, in our series of heavily pretreated patients receiving IP carboplatin, eight patients remained free of disease progression for more than 2 years. Further trials of IP carboplatin are indicated.
Carboplatin in the treatment of carcinoma of the ovary: the National Cancer Institute of Canada experience. Ovarian Cancer Subcommittee. [2018]The National Cancer Institute of Canada Clinical Trials Group has used carboplatin in two studies in women with ovarian carcinoma. In a phase II study, carboplatin produced a clinical response rate of 28% among patients with tumor persistence or recurrence following one prior cisplatin-containing regimen. Carboplatin was most efficacious in those with smaller tumors, in those who had the best responses to prior cisplatin therapy, and in those with longer intervals between the primary cisplatin treatment and the secondary carboplatin course. In this setting, a starting dose of 320 mg/m2 is suggested. A phase III randomized trial of first-line therapy compared the efficacy of cyclophosphamide/cisplatin with cyclophosphamide/carboplatin. Four hundred eighteen eligible patients were enrolled. The regimens demonstrated comparable efficacy; however, the carboplatin-based regimen was more easily administered and caused less symptomatic toxicity. The long-term results in this population with macroscopic residual disease remain disappointing.
Carboplatin in the first-line chemotherapy of ovarian cancer. [2018]When used as first-line treatment for advanced ovarian cancer in phase III trials, single-agent carboplatin has produced clinical complete response rates comparable with or exceeding those of single-agent cisplatin. Phase I/II trials of combination chemotherapy have yielded overall objective response rates of 44% to 75% when carboplatin was combined with either cyclophosphamide or chlorambucil. In randomized phase III trials of carboplatin combination chemotherapy, response rates similar to those of cisplatin combinations have been achieved but with greatly reduced toxicities. The data from these phase I, II, and III trials show that carboplatin is as active as cisplatin in patients with advanced ovarian cancer and is associated with a significantly lower incidence and is associated with a significantly lower incidence of emesis, ototoxicity, peripheral neuropathy, and renal dysfunction. Thus, carboplatin should be considered the platinum compound of choice in the firstline treatment of advanced ovarian cancer.
Optimal dosing with carboplatin. [2018]Carboplatin is a new cisplatin analogue that has a spectrum of activity similar to that of the parent compound. Since the dose intensity of cisplatin is important in achieving optimal results, it is probable that carboplatin dosage is an important factor in maximizing efficacy, particularly in platinum-sensitive tumors. Renal function and prior history of chemotherapy are the most important factors in selecting an individual patient's dose. In ovarian cancer patients, the usual dose of carboplatin will be 300 to 400 mg/m2 and will depend upon whether carboplatin is used as salvage therapy or as part of an induction combination chemotherapy regimen in previously untreated patients.
[Phase II study of carboplatin in ovarian cancer]. [2013]A phase II study of carboplatin was conducted in ovarian cancer by a cooperative study group consisting of 22 institutions nationwide. The overall response rate of 50 evaluable cases was 38.0%. The response rate in cases with no prior chemotherapy was 54.2% and that with prior chemotherapy was 23.1%. In addition, the response rate was 26.3% in cases that received prior CDDP-based chemotherapy. Histologically, the response rate was high in serous cystadenocarcinoma and endometrioid adenocarcinoma. Hematologic toxicities, particularly leukopenia and thrombocytopenia, were frequently observed, but well tolerated, while renal and neurologic toxicities were rare. These results suggested that carboplatin is useful in the treatment of ovarian cancer.
Phase II study of carboplatin in patients with ovarian carcinoma: a National Cancer Institute of Canada Clinical Trials Group Study. [2013]The National Cancer Institute of Canada Clinical Trials Group conducted a phase II study of carboplatin (400 mg/m2) given as an iv bolus every 4 weeks in patients with measurable advanced ovarian cancer who had failed or relapsed following standard platinum-containing therapy. Four complete and eight partial responses were seen in 43 evaluable patients. Toxicity was primarily hematologic. Myelosuppression, particularly thrombocytopenia, was severe in one-third of patients treated at the 400-mg/m2 starting dose. Carboplatin has antitumor activity in this clinical setting, but a lower starting dose is recommended.
Carboplatin and recurrent childhood brain tumors. [2017]Carboplatin, a cisplatin analogue, was administered as an intravenous (IV) one-hour infusion in a 4-consecutive weekly dose schedule to 44 patients with recurrent childhood brain tumors. Twenty-four patients were registered on our phase I, and 20 on our phase II studies. The maximum tolerable dose derived from our phase I study was 210 mg/m2/wk in patients with solid tumors, and the recommended dose for subsequent pediatric phase II studies was 175 mg/m2/wk. This dose was administered to 14 patients in the phase I and all 20 patients in the phase II study. Nine of 36 (25%) evaluable patients in the combined studies experienced objective responses for a median duration of 10+ months. Seven of nine responders had received prior cisplatin. Disease-specific response rates were as follows: medulloblastoma, six of 14 (43%) with three complete (CR) and three partial responses (PR); pineoblastoma, one of one (PR); germinoma, one of two (CR); and brainstem glioma, one of eight (13%) (PR). Carboplatin had mild emetic effects but no significant auditory or renal toxicity. Thrombocytopenia (less than 49,000) was encountered in nine of 28 (32%) evaluable trials at a dose of 175 mg/m2/wk. Because of its low potential for auditory, renal, and emetic toxicity, ease of administration, and high disease-specific activity, carboplatin deserves further study in multiagent phase II and III trials, especially in chemotherapy-sensitive diseases such as medulloblastoma.
Carboplatin reinduction after taxane in patients with platinum-refractory epithelial ovarian cancer. [2017]To determine the activity of carboplatin in patients with ovarian cancer who progressed on taxane (paclitaxel or docetaxel) therapy.
Preliminary results of a dose-finding study of paclitaxel and carboplatin in patients with advanced non-small cell lung cancer. [2015]This ongoing phase I study sought to establish the maximum tolerated dose of the combination of carboplatin and paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) given without routine growth factor support to previously untreated patients with stage IIIB and IV non-small cell lung cancer. Paclitaxel was administered as a 3-hour intravenous infusion. The carboplatin infusion was administered over 30 minutes immediately afterward. Patients were assigned sequentially to one of eight treatment groups in which paclitaxel and carboplatin were administered in doses ranging from 130 to 185 mg/m2 and from 230 to 350 mg/m2, respectively. Twenty-four patients have been treated to date, and the maximum tolerated dose has been reached at paclitaxel 185 mg/m2 and carboplatin 350 mg/m2. The combination has an excellent safety profile, with only a few, short-lasting episodes of neutropenia observed and no evidence of infection. At the doses tested, thrombocytopenia has not occurred.
Carboplatin plus paclitaxel in the treatment of gynecologic malignancies: the Cleveland Clinic experience. [2015]To examine the toxicity profile and antineoplastic activity of carboplatin (area under the concentration-time curve of 4 to 7.5) plus 3-hour infusional paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) (135 or 175 mg/m2) in women with advanced gynecologic malignancies, we retrospectively reviewed the experience of the Gynecologic Cancer Program at The Cleveland Clinic with this combination chemotherapy regimen. To date, 92 patients (median age, 67 years) have received a total of 460 courses (median number per patient, six) of this two-drug combination. The initial paclitaxel dose was 175 mg/m2 and the carboplatin area under the concentration-time curve was > or = 5 in 72% and 73% of patients, respectively. The major toxicity was neutropenia (grade 4 in 9% of patients), resulting in two febrile episodes and a single septic death. Grade 4 thrombocytopenia and grade 3 peripheral neuropathy were noted in one and two patients, respectively. Twelve patients (13%) experienced at least one episode of paclitaxel-associated hypersensitivity, but all were able to continue with the treatment program. Of the 62 patients with ovarian cancer or primary peritoneal carcinoma with carbohydrate antigen-125 levels > or = 60 U/mL before the initiation of chemotherapy, 74% exhibited a > or = 90% decline in the tumor marker following treatment. We conclude that the combination of carboplatin and 3-hour infusional paclitaxel can be administered in the outpatient setting with a highly acceptable toxicity profile and with major activity in patients with ovarian cancer and primary carcinoma of the peritoneum.
A phase I study of cisplatin i.p. and carboplatin i.v. with G-CSF in patients with ovarian cancer. [2019]We conducted a dose-escalation study with a fixed dose of intraperitoneal cisplatin and G-CSF support of carboplatin using the Calvert formula in epithelial ovarian cancer. Twenty-five patients were entered in this study. On day 1, carboplatin was administered intravenously at target AUCs of 4, 5, 6, and 7. On day 2, cisplatin was given i.p. in 70 mg/m2. G-CSF, 50 microgram/m2, was administered subcutaneously from day 7 to 16. Cycles were scheduled to be delivered every four weeks. A total of 85 cycles were administered. The maximum tolerated dose was AUC 7 mg/ml x min of carboplatin. The overall response rate was 80% (12/15). The combination in this regimen is feasible, and a phase II study of this regimen is warranted.
A phase II trial of pemetrexed in combination with carboplatin in patients with recurrent ovarian or primary peritoneal cancer. [2015]Carboplatin-based combinations are commonly used in platinum-sensitive ovarian cancer (PSOC). Pemetrexed in combination with carboplatin has been shown to be feasible in a phase I study in PSOC. The primary objective of this subsequent phase II study was to determine the overall response rate (ORR; defined by Response Evaluation Criteria in Solid Tumors) of this combination in patients with recurrent PSOC. Secondary objectives included progression-free survival (PFS), overall survival (OS), and toxicity.