70 Participants Needed

Erlotinib + Tyrosine Kinase Inhibitors for Cancer

AP
NM
SJ
DR
Overseen ByDTC Referral Coordinators
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Trial Summary

What is the purpose of this trial?

Cancers that return or spread after their first line of treatment are often difficult to treat with limited next step options. Based on preclinical studies, the EGFR-targeting tyrosine kinase inhibitor (TKI) Erlotinib may be better in stopping or slowing the growth of tumors when given in combination with the multitargeting TKI Lenvatinib or Axitinib. Participants will be screened with a physical exam and tests including urine and blood tests, imaging scans, and a test of their heart function. Erlotinib, axitinib, and lenvatinib are all capsules taken by mouth. All participants will take their drugs at home every day. Some participants will take erlotinib plus lenvatinib once a day. Some participants will take erlotinib once a day and axitinib twice a day. Assignment to one of the treatment arms will be determined by the study. Participants will record their doses in a diary. Treatment is given in 28-day cycles. All participants will have 4 clinic visits during their first treatment cycle. After that, they will have a clinic visit at the start of each new cycle. Imaging scans, blood and urine tests, and other tests will be repeated during various clinic visits. Participants will remain in the study for as long as the treatment is helping them. They will have follow-up phone calls after they stop treatment....

Do I need to stop my current medications to join the trial?

The trial requires that you stop taking certain medications, specifically strong CYP3A4- and/or CYP1A2-inhibiting or -inducing agents, and agents that increase gastric pH, unless they can be replaced with alternatives. If you are on more than two blood pressure medications, you will also need to adjust your treatment. Please discuss with your doctor to see if your current medications are affected.

What data supports the effectiveness of the drug Lenvatinib in cancer treatment?

Lenvatinib has shown effectiveness in treating various cancers by blocking certain proteins that help tumors grow and form new blood vessels. It has been effective in multiple cancer types and is generally safe to use.12345

What safety information is available for Erlotinib and Axitinib in humans?

Erlotinib and Axitinib are generally well tolerated in humans, but they can cause some side effects. For Erlotinib, common side effects include diarrhea and skin rash, and there is a report of hand-foot syndrome (a skin reaction on the palms and soles). Axitinib can cause diarrhea, high blood pressure, fatigue, nausea, and vomiting. Monitoring and managing these side effects can help ensure the treatment is effective.678910

What makes the drug combination of Erlotinib, Axitinib, and Lenvatinib unique for cancer treatment?

This drug combination is unique because it targets multiple pathways involved in cancer growth. Erlotinib inhibits the HER1/EGFR pathway, which is crucial for tumor survival, while Axitinib and Lenvatinib target other tyrosine kinases, potentially offering a more comprehensive approach to stopping cancer cell growth compared to treatments that target a single pathway.711121314

Research Team

SJ

Sarah J Shin, M.D.

Principal Investigator

National Cancer Institute (NCI)

Eligibility Criteria

Adults over 18 with advanced solid tumors that have worsened after treatment or for which no standard treatment exists. They must be able to swallow pills, not have severe infections like AIDS, and should have stable vital organ functions. People with certain heart conditions, those on specific drugs that affect the trial medications, smokers, pregnant or breastfeeding women are excluded.

Inclusion Criteria

Patients must have evaluable disease according to RECIST 1.1 criteria.
Patients must have <= 1+ proteinuria on urinalysis, or < 1 g protein on 24-hour urine collection, or a urine protein:creatinine ratio of < 1.
I am 18 years old or older.
See 12 more

Exclusion Criteria

History of allergic reactions attributed to compounds of similar chemical or biologic composition to study drugs.
Patients who are receiving any investigational agents are excluded.
I am not pregnant or breastfeeding.
See 8 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks
1 visit (in-person)

Treatment

Participants receive erlotinib in combination with either lenvatinib or axitinib in 28-day cycles. Treatment continues as long as it is effective.

28-day cycles, up to 30 months
4 visits during the first cycle, then 1 visit per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks
Follow-up phone calls

Treatment Details

Interventions

  • Axitinib
  • Erlotinib
  • Lenvatinib
Trial OverviewThe study is testing combinations of oral capsules: Erlotinib with either Lenvatinib or Axitinib in adults to see if these can stop tumor growth or shrink them. Participants will take these medications daily at home and attend clinic visits for monitoring through various tests including imaging scans.
Participant Groups
2Treatment groups
Experimental Treatment
Group I: BExperimental Treatment2 Interventions
Erlotinib with axitinib combination
Group II: AExperimental Treatment2 Interventions
Erlotinib with lenvatinib combination

Axitinib is already approved in European Union, United States, United Kingdom for the following indications:

🇪🇺
Approved in European Union as Inlyta for:
  • Renal cell carcinoma
🇺🇸
Approved in United States as Inlyta for:
  • Advanced renal cell carcinoma
🇬🇧
Approved in United Kingdom as Inlyta for:
  • Advanced renal cell carcinoma

Find a Clinic Near You

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials
14,080
Recruited
41,180,000+

Findings from Research

Lenvatinib, a multitargeted Tyrosine Kinase Inhibitor, has shown significant improvement in Progression-Free Survival (PFS) for patients with aggressive Differentiated Thyroid Cancer (DTC) not responsive to radioiodine, with a median PFS of 18.2 months compared to 3.6 months for placebo.
While lenvatinib is effective, it is associated with a high rate of adverse effects (over 40%), including hypertension and fatigue, and about 14% of patients may need to discontinue treatment due to these side effects.
Lenvatinib in the Therapy of Aggressive Thyroid Cancer: State of the Art and New Perspectives with Patents Recently Applied.Ferrari, SM., Ruffilli, I., Centanni, M., et al.[2018]
Lenvatinib is an effective oral treatment for various cancers, including thyroid, liver, kidney, and endometrial cancers, and can be used alone or in combination with other therapies, based on extensive clinical trial data.
The dosing strategies for lenvatinib have been carefully established to maximize patient benefits while managing side effects, which are similar to those of other tyrosine kinase inhibitors.
Lenvatinib dose, efficacy, and safety in the treatment of multiple malignancies.Motzer, RJ., Taylor, MH., Evans, TRJ., et al.[2023]
In a Phase I study with 15 healthy volunteers, the inhibition of P-glycoprotein (P-gp) by single-dose rifampicin increased the exposure of lenvatinib by approximately 32% for free and 31% for total concentrations, suggesting that P-gp plays a role in lenvatinib pharmacokinetics.
Conversely, multiple-dose rifampicin, which induces both P-gp and CYP3A4, decreased lenvatinib exposure by 18% for total and 9% for free concentrations, but these changes were small and likely not clinically significant.
Effect of rifampicin on the pharmacokinetics of lenvatinib in healthy adults.Shumaker, RC., Aluri, J., Fan, J., et al.[2021]

References

1.United Arab Emiratespubmed.ncbi.nlm.nih.gov
Lenvatinib in the Therapy of Aggressive Thyroid Cancer: State of the Art and New Perspectives with Patents Recently Applied. [2018]
Lenvatinib dose, efficacy, and safety in the treatment of multiple malignancies. [2023]
Lenvatinib, an angiogenesis inhibitor targeting VEGFR/FGFR, shows broad antitumor activity in human tumor xenograft models associated with microvessel density and pericyte coverage. [2022]
Effects of Ketoconazole on the Pharmacokinetics of Lenvatinib (E7080) in Healthy Participants. [2019]
Effect of rifampicin on the pharmacokinetics of lenvatinib in healthy adults. [2021]
Axitinib for the treatment of metastatic renal cell carcinoma: recommendations for therapy management to optimize outcomes. [2018]
Erlotinib in advanced non-small cell lung cancer: efficacy and safety findings of the global phase IV Tarceva Lung Cancer Survival Treatment study. [2018]
Erlotinib (Tarceva) for advanced non-small cell lung cancer. [2015]
Management of BRAF and MEK inhibitor toxicities in patients with metastatic melanoma. [2022]
[Hand-foot syndrome: A new side effect of erlotinib]. [2018]
11.United Statespubmed.ncbi.nlm.nih.gov
Enhanced sensitivity to the HER1/epidermal growth factor receptor tyrosine kinase inhibitor erlotinib hydrochloride in chemotherapy-resistant tumor cell lines. [2022]
12.United Statespubmed.ncbi.nlm.nih.gov
Erlotinib: small-molecule targeted therapy in the treatment of non-small-cell lung cancer. [2018]
Targeting HER1/EGFR in cancer therapy: experience with erlotinib. [2018]
Antitumor activity of HER1/EGFR tyrosine kinase inhibitor erlotinib, alone and in combination with CPT-11 (irinotecan) in human colorectal cancer xenograft models. [2018]