Erlotinib + Irinotecan for Advanced Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: Anticonvulsants, Antiretrovirals

Disqualifiers: Heart disease, Infections, Seizures, others

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

Compensation: Varies

Number of Visits: 1

Duration: 21 days per cycle

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of two treatments: erlotinib (a targeted cancer therapy) and irinotecan (a chemotherapy drug) for individuals with advanced solid tumors that have high levels of epidermal growth factor receptor (EGFR). The goal is to determine if these drugs together can halt tumor growth more effectively than current options. Participants should have a tumor type that overexpresses EGFR, lack effective treatment options, and be willing to provide biological samples. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

Do I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot take certain medications like grapefruit products, smoking, enzyme-inducing anticonvulsants, or combination antiretroviral therapy during the study. It's best to discuss your current medications with the trial team to see if any need to be stopped.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that erlotinib and irinotecan have been studied together for treating advanced cancers. Erlotinib has helped some patients with advanced lung cancer live longer, while irinotecan has also shown promise in treating various cancers.

Studies found that the combination of erlotinib and irinotecan was generally well-tolerated. Common side effects included tiredness, diarrhea, and skin rash, which are typical with cancer treatments. Most patients managed these effects without serious problems.

This trial is in its early stage (Phase 1), focusing on safety and determining the best dose. Safety data is still being gathered. However, since both drugs are already used for other conditions, there is some confidence in their safety. Always consult a healthcare provider about any concerns. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of erlotinib hydrochloride and irinotecan hydrochloride for advanced cancer because it introduces a novel approach by combining an enzyme inhibitor with chemotherapy. Erlotinib specifically targets and blocks the action of certain proteins involved in cancer cell growth, which can enhance the effectiveness of irinotecan, a chemotherapy drug that disrupts DNA replication in cancer cells. This combination could potentially offer a more powerful attack on cancer cells than using chemotherapy alone, providing hope for improved outcomes in patients with advanced cancer.

What evidence suggests that combining erlotinib and irinotecan could be effective for advanced cancer?

This trial will evaluate the combination of erlotinib hydrochloride and irinotecan hydrochloride for treating advanced solid tumors. Research has shown that erlotinib, which blocks proteins that aid tumor growth, combined with irinotecan, a chemotherapy drug that prevents tumor cell multiplication, might effectively treat these tumors. Studies have found that these two drugs can work well together, potentially killing more tumor cells than when used separately. Previous patients generally tolerated this combination without many serious side effects, suggesting that the treatment might help control the growth of advanced cancers. ^{1 2 3 4 6}

Who Is on the Research Team?

Henry C Pitot

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

This trial is for patients with advanced solid tumors that can't be surgically removed and have no curative or life-extending treatments available. Participants must not have heart disease, active infections, recent injuries, or brain metastases. They should not be pregnant/nursing and must agree to use contraception. No prior EGFR-targeting therapy or certain medications are allowed.

Inclusion Criteria

My eye exam with special dyes showed no abnormalities.

It has been over 4 weeks since my last immunotherapy or biologic treatment.

I am not currently on any immunotherapy treatments.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-Treatment

Participants receive oral erlotinib hydrochloride daily on days -6 to -1

1 week

Daily visits (in-person or virtual)

Treatment

Participants receive irinotecan hydrochloride IV on day 1 and oral erlotinib once daily on days 1-21. Courses repeat every 21 days.

21 days per cycle

1 visit (in-person) for IV administration, daily oral medication

Dose Escalation

Cohorts of 3-6 patients receive escalating doses until the MTD is determined.

Variable, based on dose escalation

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Erlotinib Hydrochloride
• Irinotecan Hydrochloride

Trial Overview The study tests combining Erlotinib Hydrochloride (which blocks enzymes aiding tumor growth) with Irinotecan Hydrochloride (chemotherapy). The goal is to see if this combination is more effective in killing tumor cells than when these drugs are used separately.

How Is the Trial Designed?

Group I: Treatment (enzyme inhibitor, chemotherapy) Experimental Treatment 2 Interventions

Patients receive oral erlotinib hydrochloride daily on days -6 to -1. Patients then receive irinotecan hydrochloride IV over 90 minutes on day 1 and oral erlotinib hydrochloride once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Irinotecan hydrochloride, approved in 1996 for second-line treatment of metastatic colorectal cancer, is generally well tolerated and can be safely administered on an outpatient basis, demonstrating clinically relevant activity against the disease.

Both irinotecan and gemcitabine, which will be discussed in a subsequent article, have manageable side effects that can be addressed with proper monitoring and dose adjustments, highlighting the importance of oncology nurses in patient education and symptom management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New agents in gastrointestinal malignancies: Part 1: Irinotecan in clinical practice. Stucky-Marshall, L.[2019]

The combination of irinotecan, epirubicin, and capecitabine has shown an acceptable toxicity profile in an open-label phase I study involving patients with metastatic adenocarcinomas, indicating it may be a safe treatment option.

The study is still ongoing, as the dose-limiting toxicity has not yet been reached, and further investigations will determine the optimal sequencing of the regimen to enhance clinical efficacy in treating upper gastrointestinal malignancies and breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irinotecan, epirubicin, and capecitabine in metastatic adenocarcinomas: preliminary results of a phase I study. Becerra, CR.[2018]

Irinotecan is an effective treatment for advanced colorectal cancer, particularly as a first-line therapy and for patients who do not respond to fluorouracil-based treatments.

The drug also shows potential activity against lung cancer and other types of cancers, but it can cause significant side effects, including myelosuppression and diarrhea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irinotecan: a new antineoplastic agent for the management of colorectal cancer. Cersosimo, RJ.[2018]

In a phase II study involving 77 previously untreated patients with metastatic colorectal cancer, the combination of capecitabine, irinotecan, and bevacizumab showed a promising progression-free survival rate of 61% at 9 months, with median overall survival of 24.8 months.

While 62% of patients experienced at least one severe adverse event, the regimen was generally well-tolerated, and quality of life remained stable throughout the treatment cycles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Capecitabine and irinotecan with bevacizumab 2-weekly for metastatic colorectal cancer: the phase II AVAXIRI study. Garcia-Alfonso, P., Chaves, M., Muñoz, A., et al.[2018]

Irinotecan hydrochloride demonstrated efficacy as a salvage therapy for recurrent and refractory non-Hodgkin lymphoma, achieving a response rate of 37.8% with complete remission in 2 patients and partial remission in 15 patients among 45 evaluable patients.

The treatment was associated with significant adverse effects, including myelosuppression and gastrointestinal toxicity, leading to dose adjustments in about 67% of patients, highlighting the need for careful management of side effects during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irinotecan hydrochloride for the treatment of recurrent and refractory non-Hodgkin lymphoma: a single institution experience. Sugiyama, K., Omachi, K., Fujiwara, K., et al.[2019]

In a study of 92 patients with advanced colorectal cancer, the combination of oxaliplatin and irinotecan showed a significantly higher response rate (43.5% vs. 19.6%) and longer progression-free survival (7.1 months vs. 5.0 months) compared to raltitrexed, indicating its effectiveness as a first-line treatment.

While the combination therapy resulted in more side effects, including neutropenia and gastrointestinal issues, adjusting the irinotecan dose improved tolerance, suggesting that oxaliplatin/irinotecan can be a beneficial treatment option with manageable toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized multicenter phase II trial of oxaliplatin plus irinotecan versus raltitrexed as first-line treatment in advanced colorectal cancer. Scheithauer, W., Kornek, GV., Raderer, M., et al.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT01646892

Study Details | Erlotinib Hydrochloride and Irinotecan ... Phase I trial to study the effectiveness of combining erlotinib hydrochloride with irinotecan hydrochloride in treating patients who have advanced solid ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/18936940/

Dose finding study of erlotinib combined to capecitabine ... Conclusions: The results documented that erlotinib at the dose of 100 mg per day, irinotecan 180 mg/m(2) and capecitabine 1,500 mg/m(2) per day for 14 days has ...

3. withpower.com withpower.com/trial/phase-1-5-2002-37d7f

Erlotinib + Irinotecan for Advanced Cancer Phase I trial to study the effectiveness of combining erlotinib hydrochloride with irinotecan hydrochloride in treating patients who have advanced solid ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT00045201?term=AREA%5BBasicSearch%5D(ERLOTINIB%20HYDROCHLORIDE)&rank=8

Study Details | Erlotinib Hydrochloride and Irinotecan ... A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.

5. sciencedirect.com sciencedirect.com/science/article/pii/S0305737222001785

Second-line treatment options for patients with metastatic ... Many of the publications reported positive results: they showed that the treatments generally worked and did not cause too many serious side effects. Liposomal ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/15475439/

Phase I trial of irinotecan, infusional 5-fluorouracil, and ... This phase I study was conducted to establish the dose-limiting toxicities and maximum-tolerated dose of erlotinib, an oral epidermal growth factor receptor ...