Erlotinib + Irinotecan for Advanced Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

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

60 Participants Needed

Trial Summary

What is the purpose of this trial?

Phase I trial to study the effectiveness of combining erlotinib hydrochloride with irinotecan hydrochloride in treating patients who have advanced solid tumors. Erlotinib hydrochloride may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining erlotinib hydrochloride and chemotherapy may kill more tumor cells.

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.

What data supports the effectiveness of the drug combination of Erlotinib and Irinotecan for advanced cancer?

Erlotinib has been shown to prolong survival in patients with advanced non-small-cell lung cancer, and Irinotecan has demonstrated promising activity in advanced colorectal cancer when combined with other drugs. These findings suggest potential effectiveness of the combination for advanced cancer, although direct evidence for this specific combination is not provided. ^{1 2 3 4 5}

Is the combination of Erlotinib and Irinotecan generally safe for humans?

Irinotecan has been used safely in treating various cancers, including colorectal and pancreatic cancer, with manageable side effects when monitored properly. It has been generally well tolerated in large patient populations, although rare adverse reactions like dysarthria (difficulty speaking) have been reported. ^{6 7 8 9 10}

What makes the drug combination of Erlotinib and Irinotecan unique for advanced cancer treatment?

The combination of Erlotinib and Irinotecan is unique because Erlotinib, an EGFR inhibitor, may enhance the effectiveness of chemotherapy by restoring sensitivity to drugs like Irinotecan, which is used for various cancers including colorectal and pancreatic cancer. This combination targets cancer cells in a novel way by potentially overcoming resistance to chemotherapy. ^{3 5 7 11 12}

Research Team

Henry C Pitot

Principal Investigator

Mayo Clinic

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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, 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]

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]

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]

References

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

Randomized multicenter phase II trial of oxaliplatin plus irinotecan versus raltitrexed as first-line treatment in advanced colorectal cancer. [2018]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Efficacy and safety of erlotinib in patients with locally advanced or metastatic breast cancer. [2021]

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

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

4. England pubmed.ncbi.nlm.nih.gov

Capecitabine and irinotecan with bevacizumab 2-weekly for metastatic colorectal cancer: the phase II AVAXIRI study. [2018]

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

A randomized, phase II, biomarker-selected study comparing erlotinib to erlotinib intercalated with chemotherapy in first-line therapy for advanced non-small-cell lung cancer. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Dysarthria induced by irinotecan in a patient with colorectal cancer. [2019]

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

New agents in gastrointestinal malignancies: Part 1: Irinotecan in clinical practice. [2019]

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

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

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

Irinotecan hydrochloride for the treatment of recurrent and refractory non-Hodgkin lymphoma: a single institution experience. [2019]

10. England pubmed.ncbi.nlm.nih.gov

Post-marketing surveillance (PMS) of all patients treated with irinotecan in Japan: clinical experience and ADR profile of 13,935 patients. [2018]

11. Greece pubmed.ncbi.nlm.nih.gov

Does erlotinib restore chemosensitivity to chemotherapy in pancreatic cancer? A case series. [2015]

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

The safety and efficacy of the weekly dosing of irinotecan for platinum- and taxanes-resistant epithelial ovarian cancer. [2018]