Iohexol-aided Carboplatin Dosing for Cancer
Recruiting in Palo Alto (17 mi)
+182 other locations
Overseen bySarah E Taylor
Age: 18+
Sex: Male
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: NRG Oncology
Must not be taking: NSAIDs, Diuretics, ARBs, ACEi
Disqualifiers: Allergic reactions, Kidney injury, others
No Placebo Group
Approved in 3 Jurisdictions
Trial Summary
What is the purpose of this trial?This trial studies how well iohexol helps doctors calculate the dose of carboplatin for cancer patients. By measuring kidney function more accurately, doctors can improve the effectiveness and safety of carboplatin treatment. Carboplatin is a platinum-based chemotherapy drug used to treat various cancers, known for its improved toxicity profile compared to cisplatin.
Will I have to stop taking my current medications?
The trial requires that if you are taking anti-inflammatory drugs, diuretics, or certain blood pressure medications (like ARBs or ACE inhibitors), you must keep taking them on a regular schedule for at least one week before the study. If you take these medications only as needed, you may need to adjust to a set schedule.
What data supports the effectiveness of the drug Iohexol-aided Carboplatin Dosing for Cancer?
Carboplatin, when dosed based on renal function rather than body surface area, has shown improved effectiveness and safety in treating solid tumors, including ovarian and non-small cell lung cancer. The combination of carboplatin with paclitaxel has demonstrated promising results, with higher survival rates and manageable toxicity, making it a preferred regimen in cancer treatment.
12345Is carboplatin generally safe for humans?
Carboplatin is generally considered safe for humans, with common side effects including low blood cell counts, nausea, and vomiting. It is less likely to cause kidney damage and severe nausea compared to cisplatin, another similar drug. Serious side effects like hearing loss or liver and kidney problems are rare.
13678What makes the drug Iohexol-aided Carboplatin dosing unique for cancer treatment?
This treatment is unique because it uses Iohexol to accurately measure kidney function, allowing for a more precise dosing of Carboplatin based on the patient's actual kidney performance rather than relying on less accurate creatinine-based estimates. This individualized dosing helps optimize the effectiveness of Carboplatin while minimizing potential side effects.
1391011Eligibility Criteria
This trial is for male cancer patients aged 18 or older who will receive carboplatin chemotherapy. They must be in good general health, able to follow the study plan, and provide informed consent. Men should use contraception as dictated by their treatment protocol. Women are not eligible due to study objectives.Inclusion Criteria
I am 18 years old or older.
I am male.
I am a male interested in joining the study.
+4 more
Exclusion Criteria
I've had a recent kidney injury, have sickle cell disease, or currently use nephrostomy tubes.
If you have had your whole or part of a limb amputated, you cannot participate because it can affect how a substance called iohexol spreads in your body.
Edema beyond trace edema, because this will impact iohexol equilibration and distribution
+6 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive iohexol intravenously followed by standard of care carboplatin IV, with collection of 7-8 blood samples for analysis
4 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment
3-4 weeks
Participant Groups
The trial is testing how well iohexol helps calculate the correct dose of carboplatin for cancer treatment. It aims to improve dosing accuracy of carboplatin by studying its interaction with iohexol and collecting biospecimens from participants.
1Treatment groups
Experimental Treatment
Group I: Treatment (iohexol, standard care carboplatin, blood samples)Experimental Treatment3 Interventions
Patients receive iohexol IV over 30-60 seconds. Patients then receive standard of care carboplatin IV. Patients also undergo collection of 7-8 blood samples for analysis.
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:
Tulane University Health Sciences CenterNew Orleans, LA
UC San Diego Health System - EncinitasEncinitas, CA
Broadlawns Medical CenterDes Moines, IA
Cleveland Clinic FoundationCleveland, OH
More Trial Locations
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Who Is Running the Clinical Trial?
NRG OncologyLead Sponsor
National Cancer Institute (NCI)Collaborator
References
New Perspectives on an Old Friend: Optimizing Carboplatin for the Treatment of Solid Tumors. [2019]BACKGROUND. Since its clinical introduction in 1981, carboplatin has proved a feasible alternative to cisplatin for the treatment of many solid tumors, especially ovarian cancer. Because the pharmacokinetics and, ultimately, the pharmacodynamics of carboplatin are highly dependent on the status of renal function, fixed dosing based on body surface area has led to carboplatin overdosing or, especially, underdosing. This has resulted in less than optimal treatment results compared with cisplatin in a variety of solid tumor types. Only in the past few years has the optimal dosing method for carboplatin-individualizing the dose (area under the concentration-versus-time curve [AUC]) rather than conventional use of body surface area-been adopted by clinical oncologists. METHODS. An extensive review of the oncology literature has been performed to update both carboplatin dosing guidelines as well as its present role in solid tumor chemotherapy. Initial efforts to devise a dosing formula for carboplatin focused on reducing myelotoxicity (especially thrombocytopenia). Subsequently, a simple formula was developed to adjust the carboplatin dose according to renal function. By targeting a carboplatin AUC rather than empirically dosing according to body surface area, doses of carboplatin can be individualized to fall within the drug's therapeutic index. RESULTS. The use of carboplatin dosing guidelines based on renal function has led to optimization of its pharmacodynamic effects both with respect to its safety profile and its ultimate impact on solid tumor response and patient survival. Since carboplatin has little neurotoxicity, it has become the platinum agent of choice in combination with paclitaxel for therapy of previously untreated ovarian cancer. Carboplatin plus etoposide and carboplatin plus paclitaxel have been studied in phase II and III trials, with the latter combination demonstrating improved activity against advanced non-small cell lung cancer. Additional trials in patients with other solid tumors have shown that carboplatin is more cost-effective and less toxic than cisplatin. CONCLUSIONS. Dosing based on renal function and a targeted serum AUC, rather than on body surface area, has resulted in the optimal utilization of carboplatin in cancer chemotherapy. Its predictable toxicity and clinical efficacy equivalent to cisplatin make carboplatin the drug of choice for selected tumor types.
Paclitaxel/carboplatin in the treatment of non-small-cell lung cancer. [2015]Chemotherapeutic intervention in advanced and metastatic non-small-cell lung cancer (NSCLC) has changed over the past 2 decades. The improvements offered by cisplatin (Platinol)-based regimens, though significant in terms of survival and quality of life, were modest at best. Carboplatin (Paraplatin), which possesses a toxicity profile favorable to that of its parent analogue cisplatin, yielded survival rates superior to that of the cisplatin-combination chemotherapy arms in a large randomized study of patients with metastatic non-small-cell lung cancer. With the introduction of taxanes in the early 1990s, paclitaxel (Taxol) demonstrated single-agent activity of 21% to 24%, with a 40% 1-year survival rate in metastatic disease. The next generation of phase I/II studies evaluated the efficacy of paclitaxel in combination with carboplatin. Results with this regimen have shown substantial promise, and 1-year survival rates as high as 54% have been reported. Full doses of both agents have been combined without any additional toxicity, and there appears to be a dose-response effect with paclitaxel. The combination of paclitaxel and carboplatin has been incorporated as the investigational arm of all the ongoing multicenter and cooperative group studies. While the results from these randomized studies are awaited, this combination has become the most widely used regimen in community practice for patients with non-small-cell lung cancer. It is also being evaluated for treatment at earlier disease stages, in the setting of minimal tumor burden, and in combined-modality regimens.
[Evaluation of carboplatin administration into the serous cavity in the treatment of malignant effusion]. [2013]Carboplatin, a new analogue of cisplatin, was administered into the serous cavity in nine primary lung cancer patients with malignant effusion, consisting of six malignant pleural effusions, two malignant pericardial effusions and one malignant ascites. Clinical effects, toxicities and pharmacokinetics were studied. The doses of carboplatin were 300 mg/m2 in seven patients, 200 mg/m2 in one patient and 1,100 mg/body in one patient. In seven evaluable patients, consisting of four non-small cell lung cancers and three small cell lung cancers, the response rate was 85.7% with 3 CR cases, 3 PR cases and 1 NR case. As toxicities, thrombocytopenia was observed in 57.1%, leukopenia in 57.1%, anemia in 71.4%, anorexia in 42.9%, nausea or vomiting in 28.6%, and low grade fever in 14.3%. However local pain, renal or liver dysfunction were not observed. The pharmacokinetics of free platinum concentration was analyzed with a two-compartment model (t1/2 beta = 18.60 hours) and 14.8% of total platinum remained free in effusion 24 hours after intracavitary administration. A high level of free platinum in effusion was maintained over a long period after carboplatin administration. This method was considered to be effective for the treatment of malignant effusion from the viewpoint of pharmacokinetics and less toxicity.
[Pharmacokinetics and individual dose adjustment of carboplatin]. [2013]Carboplatin differs from cisplatin by its pharmacokinetics and toxicity profile. Carboplatin is mainly eliminated by the kidneys and its dose-limiting toxicity is the bone marrow suppression. Myelosuppression of carboplatin is more closely correlated with the area under the curve (AUC) of ultrafiltrable plasma concentration versus time to which a patient is exposed, than it is with the administered dose. Similar relationships have been shown between AUC and antitumour effect, although they are in a smaller number and less close. Several methods of dosage individualisation a priori (before carboplatin administration) have been proposed. Since carboplatin is often prescribed to patients with altered renal functions, this dose optimisation is particularly justified. Dose individualisation is based on both equations allowing to predict the patient carboplatin clearance and the choice of target AUC. The different equations proposed are based on direct measurement of the renal filtration glomerular rate or on patient demographic and biological characteristics such as weight and serum creatinine. The respective advantages and limits of these equations are now well known. However, the values of optimal AUC that depend on cytotoxic drugs combined to carboplatin and the patient hematopoietic status, are not precisely determined for each protocol of chemotherapy. When carboplatin is given by reiterated administrations within each course, it is possible to adjust the last doses according to a limited number of blood samples following the first infusion and a Bayesian analysis of the observed plasma concentrations. These methodologies are more complex, but they may be useful for the intensification protocols. Carboplatin is still the only cytotoxic drug for which dose is individualised not according to the body surface area but according to pharmacokinetic parameters.
Variability of carboplatin dose calculation methods in Spain. [2019]To describe and analyze the variability in carboplatin dosing strategies in Spanish hospitals.
Results of NCI-sponsored phase I trials with carboplatin. [2019]Carboplatin has been developed for clinical trials as a less nephrotoxic, less emetogenic analog of cisplatin. In preclinical tumor models it was less potent than the parent compound on a molar basis, but reduced toxicity allowed comparable antitumor doses to be given. In phase I studies its dose-limiting toxicities were reversible myelosuppression, especially thrombocytopenia. Leucopenia and anemia occurred to a lesser degree. Other reported toxicities included nausea, vomiting, malaise, myalgia, arthralgia, ototoxicity, hypomagnesemia, and proteinuria. Nausea and vomiting occurred frequently, but was much less severe than that observed with cisplatin. The incidence of serum creatinine elevations was low. The increase was usually reversible and occurred only in association with administration of aminoglycosides, or abnormal pretreatment renal function. Recommended phase II doses by schedule are: bolus every 4 weeks, 400-500 mg/m2 (560 mg/m2 in children); 24 hour continuous infusion every 4 weeks, 320-400 mg/m2; weekly bolus for 4 consecutive weeks with 2 weeks rest, 100-125 mg/m2 (175 mg/m2 in children); bolus for 5 consecutive days every 4 weeks, 77-95 mg/m2. Objective responses were observed during these phase I studies in adult patients (head and neck, breast, renal carcinomas) and children (osteosarcoma, brain stem lesions). In addition to phase II evaluations in all major tumor types, plans for phase III studies in selected tumors are underway.
Combined carboplatin and cisplatin therapy in patients with advanced non-small cell lung cancer. [2019]Combining cisplatin and carboplatin may eliminate some of the toxic effects of each agent and permit the use of higher doses, because these agents have different pharmacodynamics and dose-limiting toxicities. We investigated the safety and efficacy of these agents in combination. The toxicity profile was evaluated in a Phase I trial in 18 patients with advanced non-small cell lung cancer (NSCLC). Carboplatin was administered in doses ranging from 200 to 400 mg/m2 on day 1 and cisplatin at a dose of 80 mg/m2 on day 3. Only one cycle of chemotherapy was administered. Thrombocytopenia was the dose-limiting toxic effect. The maximal tolerated dose of carboplatin was 350 mg/m2. We then investigated the efficacy of the optimal dose of this combined chemotherapy in a Phase II trial in 13 patients. We used a carboplatin dose of 300 mg/m2 for safety in the Phase II trial. Three of 13 patients developed grade 3-4 hematologic toxicity, which was improved without major complications. A partial response was observed in 5 of 13 patients (38.5%). Combination chemotherapy with carboplatin (day 1, 300 mg/m2) and cisplatin (day 3, 80 mg/m2) showed promising effects in patients with advanced NSCLC.
Phase I clinical and pharmacologic trial of carboplatin daily for 5 days. [2013]Twenty-two patients with refractory tumors received 64 courses of iv bolus carboplatin every day X 5, every 4-5 weeks. All patients are evaluable for toxicity and 18 are evaluable for response. For solid tumor phase II studies, a dose of 77 mg/m2/day X 5 is recommended for patients who have received prior chemotherapy. Patients with no prior chemotherapy experience should receive 99 mg/m2/day X 5. The major dose-limiting side effect is dose-related thrombocytopenia. Courses of carboplatin on this schedule should be repeated every 5 weeks to avoid cumulative wbc count toxicity, since leukopenia frequently did not occur until Day 28. Other toxic effects observed were nausea and vomiting and lower-extremity myalgias and arthralgias. There was no evidence of hearing loss, mucosal damage, or changes in liver or renal function tests of any patient while in this study. Therapeutic responses were seen in four patients: one partial response in renal cancer of 9+ months' duration; one partial response in head and neck cancer of 7+ months' duration; and objective responses in melanoma and colorectal carcinoma of 6 months' duration.
Evaluation of the pharmacokinetic drug-drug interaction potential of iohexol, a renal filtration marker. [2022]Carboplatin dose is calculated based on kidney function, commonly estimated with imperfect creatinine-based formulae. Iohexol is used to measure glomerular filtration rate (GFR) and allows calculation of a more appropriate carboplatin dose. To address potential concerns that iohexol administered during a course of chemotherapy impacts that therapy, we performed in vitro and in vivo pharmacokinetic drug-drug interaction evaluations of iohexol.
Utility of individualized carboplatin dosing alone and in combination regimens. [2018]Carboplatin represents an ideal candidate for dose optimization in individual patients. The excellent correlations between renal function and carboplatin total body clearance and between carboplatin area under the plasma concentration by time curve (AUC) and thrombocytopenia allow calculation of carboplatin dosages that simultaneously minimize the likelihood of toxicity and maximize the amount of drug that can be delivered. Current studies are defining the essential relationship between carboplatin AUC and the likelihood of achieving a therapeutic response in various tumor types. These quantitative relationships between carboplatin AUC and thrombocytopenia and AUC and response should be the foundation for the intelligent use of carboplatin as an individual agent and for the intelligent assessment of the beneficial or adverse effects of other agents when combined with carboplatin.
A sequential Bayesian algorithm for dose individualisation of carboplatin. [2013]Carboplatin is associated with significantly less nephrotoxicity and neurotoxicity than is cisplatin. The dose-limiting toxicity of carboplatin is myelotoxicity. A number of dosing methods have been described that allow a value for the area under the concentration-time curve to be targeted on the basis of the patient's renal function. Recently a formalised analysis of the pharmacodynamic response to carboplatin revealed a therapeutic window in which the response rate was maximal and toxicity, tolerable. Optimal therapy would result from targeting this window in the individual patient. The aim of this study was to develop a Bayesian dose-individualisation method for carboplatin. The method involved (1) development of a high-performance liquid chromatography (HPLC) method to measure serum concentrations of carboplatin; (2) a pharmacokinetic study in 12 women receiving carboplatin for ovarian cancer to estimate the population pharmacokinetic values for this group of patients; (3) development of population models to describe the concentration-time course of carboplatin in serum along with associated errors; and (4) development of an algorithm that uses a sequential Bayesian design, which enables estimation of future doses of carboplatin on the basis of feedback from serum concentrations. The results of each of the stages were (1) the coefficient of variation of the assay was 6.3% within day and 8.4% between days (r2 = 0.9993), and the limit of detection was 0.25 mg/l; (2) Patients' ages ranged from 49 to 68 years, their weights varied from 46 to 85 kg, and their glomerular filtration rate ranged from 3.2 to 7.4 l/h. A geometric mean clearance (Cl) of 6.8 L/h and a steady-state volume of distribution (Vss) of 221 were estimated, which are similar to previously published data; (3) and a two-compartment model best described the data. Two error models were developed, the first describing the error associated with the assay and the second, the error of the two-compartment model, i.e. error due to individual variation in pharmacokinetics and error due to model mis-specification. Finally, (4) the development of a sequential Bayesian dose-individualisation method for carboplatin is described. To our knowledge, this is the first sequential design that has been used for dose individualisation of chemotherapy. The program is specific for carboplatin and operates independently of commercially available Bayesian software. Doses predicted by this program are being tested prospectively against conventional dosing methods.