Iohexol-aided Carboplatin Dosing for Cancer

Recruiting at 211 trial locations

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: NRG Oncology

Must not be taking: NSAIDs, Diuretics, ARBs, ACEi

Disqualifiers: Allergic reactions, Kidney injury, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

350 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how well a drug called iohexol helps doctors determine the optimal dose of carboplatin for cancer treatment. Carboplatin, a chemotherapy drug, stops cancer cells from growing and spreading. By identifying the right dose, doctors aim to enhance its effectiveness in treating cancer. The study seeks male participants already receiving carboplatin treatment who can maintain a consistent medication schedule. Participants should not have severe allergies to CT contrast or recent kidney problems. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking advancements in cancer treatment.

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 prior data suggests that this protocol is safe for cancer patients?

Research has shown that carboplatin can be safer and more effective when dosed based on kidney function rather than body size, aiding in the treatment of solid tumors. However, combining carboplatin with cyclophosphamide may increase bone marrow damage, raising the risk of side effects.

Iohexol is not a treatment but assists doctors in determining the optimal dose of carboplatin. Although specific safety data for iohexol in this context is lacking, it is widely used and generally considered safe for imaging tests.

As this is an early-stage trial, safety information for this drug combination in humans remains limited. Early-phase trials primarily ensure treatments are safe for people, so researchers are still assessing how well individuals tolerate this treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores a new way to personalize carboplatin dosing for cancer treatment. Unlike the standard approach, this trial uses iohexol, a contrast agent, to help determine the precise dose of carboplatin each patient needs. This method aims to optimize effectiveness and minimize side effects by tailoring the treatment to individual patient needs. By potentially improving how carboplatin is dosed, this trial could lead to more effective and safer cancer treatments.

What evidence suggests that iohexol is effective for calculating carboplatin dosing in cancer patients?

Research shows that carboplatin is a powerful chemotherapy drug that stops cancer cells from growing and spreading. In this trial, participants will receive iohexol to determine the most precise dose of carboplatin for each individual. Iohexol enhances precision in finding the best dose. The aim is to make carboplatin more effective for each person, potentially leading to better outcomes in fighting cancer. ^{1 4 6 7 8}

Who Is on the Research Team?

Sarah E Taylor

Principal Investigator

NRG Oncology

Are You a Good Fit for This Trial?

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 male.

I am a male interested in joining the study.

The patient or a legally authorized representative must provide study-specific informed consent prior to study entry

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Biospecimen Collection
• Carboplatin

Trial Overview 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.

How Is the Trial Designed?

Group I: Treatment (iohexol, standard care carboplatin, blood samples) Experimental Treatment 3 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

Who Is Running the Clinical Trial?

NRG Oncology

Lead Sponsor

Trials

242

Recruited

105,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study involving nine lung cancer patients with malignant effusions, carboplatin showed a high response rate of 85.7%, indicating its efficacy in treating these conditions, with three complete responses and three partial responses.

The treatment was associated with manageable toxicities, primarily blood-related issues like anemia and thrombocytopenia, but did not result in severe side effects such as renal or liver dysfunction, suggesting a favorable safety profile for this method of administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Evaluation of carboplatin administration into the serous cavity in the treatment of malignant effusion]. Gotoh, T., Hiramori, N., Fujita, Y., et al.[2013]

Carboplatin is a less toxic alternative to cisplatin, allowing for comparable antitumor doses with reduced side effects, particularly in terms of nephrotoxicity and severity of nausea and vomiting.

In phase I studies involving various adult and pediatric cancers, carboplatin showed objective responses while primarily causing reversible myelosuppression, with recommended dosing strategies established for further clinical evaluation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results of NCI-sponsored phase I trials with carboplatin. Foster, BJ., Clagett-Carr, K., Leyland-Jones, B., et al.[2019]

Carboplatin dosage can be optimized for individual patients by correlating renal function with drug clearance and monitoring the area under the plasma concentration-time curve (AUC) to reduce toxicity and enhance therapeutic effects.

Understanding the relationship between carboplatin AUC and both thrombocytopenia (a drop in platelet count) and treatment response is crucial for tailoring carboplatin use and evaluating its combination with other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Utility of individualized carboplatin dosing alone and in combination regimens. Egorin, MJ., Jodrell, DI.[2018]

Carboplatin has significantly lower nephrotoxicity and neurotoxicity compared to cisplatin, making it a safer option for patients, although its dose-limiting toxicity is myelotoxicity.

The study developed a novel Bayesian dose-individualization method for carboplatin, which tailors treatment based on individual patient responses, and is currently being tested against traditional dosing methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A sequential Bayesian algorithm for dose individualisation of carboplatin. Duffull, SB., Begg, EJ., Robinson, BA., et al.[2013]

In a Phase I trial involving 18 patients with advanced non-small cell lung cancer (NSCLC), the combination of carboplatin and cisplatin was found to have a manageable toxicity profile, with thrombocytopenia being the main dose-limiting effect and a maximum tolerated dose of 350 mg/m2 for carboplatin.

In a subsequent Phase II trial with 13 patients, using a safer carboplatin dose of 300 mg/m2, 38.5% of patients showed a partial response to the treatment, indicating that this combination chemotherapy may be effective for advanced NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined carboplatin and cisplatin therapy in patients with advanced non-small cell lung cancer. Nakanishi, R., Kume, T., Mitsudomi, T., et al.[2019]

In a study involving 22 patients with refractory tumors, carboplatin was administered in 64 courses, showing therapeutic responses in four patients, including partial responses lasting up to 9 months in renal and head and neck cancers.

The major side effect observed was dose-related thrombocytopenia, but there were no significant toxicities such as hearing loss or liver/renal function changes, indicating a relatively safe profile for the recommended dosing schedule of 77 mg/m2/day for previously treated patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I clinical and pharmacologic trial of carboplatin daily for 5 days. Van Echo, DA., Egorin, MJ., Whitacre, MY., et al.[2013]

Carboplatin, when dosed based on renal function and targeted area under the concentration-versus-time curve (AUC), has shown improved safety and efficacy in treating solid tumors compared to traditional body surface area dosing.

This individualized dosing approach has made carboplatin the preferred platinum-based chemotherapy agent for ovarian cancer and has demonstrated better cost-effectiveness and lower toxicity than cisplatin in various solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Perspectives on an Old Friend: Optimizing Carboplatin for the Treatment of Solid Tumors. Alberts, DS., Dorr, RT.[2019]

Carboplatin's effectiveness and toxicity are more closely related to the area under the curve (AUC) of its plasma concentration rather than the administered dose, making dose individualization crucial, especially for patients with altered kidney function.

Methods for optimizing carboplatin dosing include predicting patient clearance using equations based on renal function and demographic factors, allowing for tailored treatment that can enhance efficacy and reduce toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pharmacokinetics and individual dose adjustment of carboplatin]. Chatelut, E., Canal, P., Bugat, R.[2013]

In a study involving female mice, the co-administration of iohexol with carboplatin did not significantly affect the exposure levels of carboplatin in plasma, kidneys, or bone marrow, suggesting that iohexol can be safely used to measure kidney function without impacting carboplatin's effectiveness.

Iohexol also did not interfere with the metabolism of other chemotherapy drugs like paclitaxel and gemcitabine, indicating that using iohexol for accurate dosing of carboplatin is unlikely to cause harmful drug interactions during chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the pharmacokinetic drug-drug interaction potential of iohexol, a renal filtration marker. Joshi, A., Guo, J., Holleran, JL., et al.[2022]

The combination of paclitaxel and carboplatin has shown promising results in treating advanced non-small-cell lung cancer (NSCLC), with reported 1-year survival rates as high as 54%, making it a widely used regimen in clinical practice.

This combination therapy has been effective without additional toxicity, allowing for full doses of both drugs to be administered, and is currently being evaluated in ongoing studies for earlier stages of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel/carboplatin in the treatment of non-small-cell lung cancer. Belani, CP.[2015]

A survey of 185 Spanish hospitals revealed that while all used the Calvert formula for carboplatin dosing, there was significant variability in how glomerular filtration rate was estimated and how doses were capped, which could impact treatment effectiveness and safety.

Most hospitals capped carboplatin doses based on creatinine clearance, with 54.8% using a cap of 125 mL/min, highlighting the need for standardized dosing practices to ensure consistent patient care across different facilities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Variability of carboplatin dose calculation methods in Spain. Cuesta-Grueso, C., Burgos-San José, A., Cajaraville-Ordoñana, G., et al.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03997370

Study Details | NCT03997370 | Evaluation of Dosing ... This trial studies how well iohexol works in helping doctors calculate the dose of carboplatin given to patients with cancer. Drugs used in chemotherapy, ...

2. uchicagomedicine.org uchicagomedicine.org/find-a-clinical-trial/clinical-trial/cirb200741

CLINICAL TRIAL / NCT03997370 This trial studies how well iohexol works in helping doctors calculate the dose of carboplatin given to patients with cancer. Drugs used in chemotherapy, ...

3. clinicaltrials.ucsd.edu clinicaltrials.ucsd.edu/trial/NCT03997370

Dosing Procedures of Chemotherapy Treatment ... This trial studies how well iohexol works in helping doctors calculate the dose of carboplatin given to patients with cancer.

4. centerwatch.com centerwatch.com/clinical-trials/listings/NCT03997370/evaluation-of-dosing-procedures-of-chemotherapy-treatment-carboplatin-with-the-contrast-agent-iohexol

Evaluation of Dosing Procedures of Chemotherapy ... This trial studies how well iohexol works in helping doctors calculate the dose of carboplatin given to patients with cancer.

5. studypages.com studypages.com/s/a-study-of-iohexol-to-evaluate-dosing-of-chemotherapy-treatment-carboplatin-in-patients-with-cancer-230580/

A Study of Iohexol to Evaluate Dosing of Chemotherapy ... This is a study for people who have cancer that is being treated with the chemotherapy drug carboplatin. This trial studies how well iohexol works in ...

6. withpower.com withpower.com/trial/phase-10-2019-53e77

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 ...

7. clinconnect.io clinconnect.io/trials/NCT03997370

Evaluation of Dosing Procedures of Chemotherapy This trial studies how well iohexol works in helping doctors calculate the dose of carboplatin given to patients with cancer. Drugs used in chemotherapy, ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/7992070/

Modeling toxicity and response in carboplatin ... - PubMed - NIH When combined with cyclophosphamide 600 mg/m2, any carboplatin AUC was found to be associated with greater myelotoxicity and a higher likelihood of both ...