Tipifarnib for Cancer

Recruiting at 180 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A4/5 drugs, Cyclosporine

Disqualifiers: Pregnancy, Uncontrolled infection, Organ transplant, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 2 years

5 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests tipifarnib, a drug that may help stop cancer growth, on children with certain advanced cancers that have a specific genetic change. The drug works by targeting and blocking the growth of these cancer cells.

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

The trial requires that you stop taking other anti-cancer agents and certain medications that affect liver enzymes (CYP3A4/5 or UGT) at least 14 days before starting tipifarnib. If you're on corticosteroids, you need to be on a stable or decreasing dose for at least 7 days before joining. Check with the study team about any other specific medications you are taking.

Is Tipifarnib safe for humans?

Tipifarnib has been studied in various clinical trials for different types of cancer, including small-cell lung cancer and advanced leukemias. These studies have looked at its safety and how well people can tolerate it, often in combination with other drugs. While specific side effects are not detailed here, the trials aimed to find the maximum doses that patients could handle, suggesting that safety is a key focus in its evaluation. ^{1 2 3 4 5}

What makes the drug Tipifarnib unique for cancer treatment?

Tipifarnib is unique because it is a farnesyltransferase inhibitor, which means it works by blocking an enzyme that helps cancer cells grow, making it different from other treatments that target blood vessels or specific growth factor receptors. ^{6 7 8 9 10}

Research Team

Christine A Pratilas

Principal Investigator

Children's Oncology Group

Eligibility Criteria

This trial is for children and young adults up to 21 years old with advanced solid tumors, lymphoma, or histiocytic disorders that have a change in the HRAS gene. They should be able to swallow tablets, have recovered from previous cancer treatments, and meet certain health criteria like blood counts. Pregnant individuals or those on certain medications are excluded.

Inclusion Criteria

I have recovered from side effects of previous cancer treatments.

I am between 12 and 21 years old.

I have received stem cell infusions and/or radiation therapy within the specified timeframes.

Exclusion Criteria

You are currently taking other medications for cancer.

I am taking medication to prevent graft-versus-host disease after a bone marrow transplant.

I have an infection that is not responding to treatment.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive tipifarnib orally or via nasogastric or gastric tube twice daily on days 1-7 and 15-21. Treatment repeats every 28 days for up to 26 cycles (2 years) in the absence of disease progression or unacceptable toxicity.

Up to 2 years

Regular visits for tumor disease evaluation and blood specimen collections

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up at 30 days and periodically thereafter.

30 days and periodically thereafter

Biomarker Analysis

Evaluation of other biomarkers as predictors of response to tipifarnib and profiling changes in tumor genomics over time.

Up to 7 years

Treatment Details

Interventions

• Tipifarnib

Trial Overview The effectiveness of Tipifarnib is being tested on patients whose cancers have returned or spread and have an HRAS gene alteration. This drug aims to block cancer cell growth linked to this genetic change and potentially shrink tumors.

Participant Groups

Group I: Treatment (tipifarnib) Experimental Treatment 7 Interventions

Patients receive tipifarnib PO or via nasogastric or gastric tube BID on days 1-7 and 15-21. Treatment repeats every 28 days for up to 26 cycles (2 years) in the absence of disease progression or unacceptable toxicity. Patients undergo tumor disease evaluation with PET scan, CT scan, MRI, or MIBG scintigraphy throughout the trial. Patients may undergo bone marrow aspiration or biopsy at baseline, or if there is suspicion of bone marrow metastasis, or when a complete or partial response is identified, or if there is disease progression in the marrow suspected. Patients may undergo blood specimen collections throughout the trial.

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

Approved in United States as Zarnestra for:

• Acute myeloid leukemia (AML)

Approved in European Union as Zarnestra for:

• Acute myeloid leukemia (AML)

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 673 cancer patients, higher systemic exposure to tipifarnib was significantly associated with increased rates of severe neutropenia and thrombocytopenia, indicating that monitoring drug levels could help manage these specific toxicities.

While some nonhaematological toxicities showed weak associations with tipifarnib exposure, the overall incidence was low, suggesting that an exposure-guided dosage adjustment may not be necessary for managing these side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exposure-toxicity relationships for tipifarnib in cancer patients. Perez-Ruixo, JJ., Chen, W., Zhang, S., et al.[2018]

Cediranib, when used in combination with chemotherapy and as maintenance therapy, significantly improved progression-free survival (PFS) in women with platinum-sensitive ovarian cancer, showing a hazard ratio of 0.56, indicating a 44% reduction in the risk of disease progression.

While the overall survival (OS) analysis was underpowered due to a reduced number of participants, there was a 14% relative reduction in the risk of death, suggesting that cediranib may still provide meaningful benefits in extending survival time for patients with recurrent ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cediranib in addition to chemotherapy for women with relapsed platinum-sensitive ovarian cancer (ICON6): overall survival results of a phase III randomised trial. Ledermann, JA., Embleton-Thirsk, AC., Perren, TJ., et al.[2021]

In a phase I study involving 21 patients with advanced solid tumors, the combination of olaparib and topotecan was found to have a maximum tolerated dose (MTD) of topotecan 1.0 mg/m²/day for 3 days plus olaparib 100 mg twice daily, primarily due to dose-limiting toxicities like neutropenia and thrombocytopenia.

The study highlighted that while the combination treatment was associated with common adverse events such as fatigue and gastrointestinal issues, the significant hematological side effects led to the decision not to pursue further development of this treatment combination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of the poly(ADP-ribose) polymerase (PARP) inhibitor, olaparib (AZD2281) in combination with topotecan for the treatment of patients with advanced solid tumors: a phase I study. Samol, J., Ranson, M., Scott, E., et al.[2022]

References

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

Phase II study of the farnesyl transferase inhibitor R115777 in patients with sensitive relapse small-cell lung cancer. [2020]

2. England pubmed.ncbi.nlm.nih.gov

Exposure-toxicity relationships for tipifarnib in cancer patients. [2018]

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

A phase I clinical-pharmacodynamic study of the farnesyltransferase inhibitor tipifarnib in combination with the proteasome inhibitor bortezomib in advanced acute leukemias. [2021]

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

A phase I clinical and pharmacokinetic study of tipifarnib in combination with docetaxel in patients with advanced solid malignancies. [2019]

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

Phase I trial and pharmacokinetic study of the farnesyltransferase inhibitor tipifarnib in children with refractory solid tumors or neurofibromatosis type I and plexiform neurofibromas. [2016]

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

Cediranib in addition to chemotherapy for women with relapsed platinum-sensitive ovarian cancer (ICON6): overall survival results of a phase III randomised trial. [2021]

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

Safety and tolerability of the poly(ADP-ribose) polymerase (PARP) inhibitor, olaparib (AZD2281) in combination with topotecan for the treatment of patients with advanced solid tumors: a phase I study. [2022]

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

Phase II, open-label study of pazopanib or lapatinib monotherapy compared with pazopanib plus lapatinib combination therapy in patients with advanced and recurrent cervical cancer. [2022]

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

Phase I pharmacokinetic study of the safety and tolerability of lapatinib (GW572016) in combination with oxaliplatin/fluorouracil/leucovorin (FOLFOX4) in patients with solid tumors. [2018]

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

A phase I and pharmacokinetic study of lapatinib in combination with infusional 5-fluorouracil, leucovorin and irinotecan. [2020]