Iohexol-aided Carboplatin Dosing for Cancer

Recruiting at 182 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

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. ^{1 2 3 4 5}

Is 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. ^{1 3 6 7 8}

What 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. ^{1 3 9 10 11}

Research Team

Sarah E Taylor

Principal Investigator

NRG Oncology

Eligibility 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.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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'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]

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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

New Perspectives on an Old Friend: Optimizing Carboplatin for the Treatment of Solid Tumors. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

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

3. Japan pubmed.ncbi.nlm.nih.gov

[Evaluation of carboplatin administration into the serous cavity in the treatment of malignant effusion]. [2013]

4. France pubmed.ncbi.nlm.nih.gov

[Pharmacokinetics and individual dose adjustment of carboplatin]. [2013]

5. England pubmed.ncbi.nlm.nih.gov

Variability of carboplatin dose calculation methods in Spain. [2019]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Results of NCI-sponsored phase I trials with carboplatin. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Combined carboplatin and cisplatin therapy in patients with advanced non-small cell lung cancer. [2019]

8. United States pubmed.ncbi.nlm.nih.gov

Phase I clinical and pharmacologic trial of carboplatin daily for 5 days. [2013]

9. Germany pubmed.ncbi.nlm.nih.gov

Evaluation of the pharmacokinetic drug-drug interaction potential of iohexol, a renal filtration marker. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Utility of individualized carboplatin dosing alone and in combination regimens. [2018]

11. Germany pubmed.ncbi.nlm.nih.gov

A sequential Bayesian algorithm for dose individualisation of carboplatin. [2013]