Tipifarnib for Cancer

Not currently recruiting at 190 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the drug tipifarnib (also known as Zarnestra) to determine its effectiveness in treating solid tumors, lymphoma, or histiocytic disorders in children and young adults. The focus is on cases where these cancers have returned or spread and have a specific genetic change called HRAS. Tipifarnib may shrink tumors by blocking their growth. Ideal candidates have a solid tumor, lymphoma, or histiocytic disorder with the HRAS mutation and measurable disease on scans. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of participants.

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 there any evidence suggesting that tipifarnib is likely to be safe for humans?

Research has shown that tipifarnib is generally safe for patients. Several studies have found the side effects to be manageable. In trials with head and neck cancer patients who have HRAS mutations, most participants tolerated tipifarnib well. Another study on patients with aggressive lymphoma also found it safe and manageable. Overall, extensive testing has established the safety of tipifarnib. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Tipifarnib is unique because it targets a specific enzyme called farnesyltransferase, which plays a role in the growth and survival of cancer cells. Unlike standard chemotherapy that broadly attacks rapidly dividing cells, tipifarnib specifically disrupts the signaling pathways essential for cancer cell proliferation. This targeted approach could lead to fewer side effects and improved effectiveness for patients. Researchers are excited about tipifarnib because it offers a more precise method of shutting down cancer cell growth, potentially leading to better outcomes and a higher quality of life for patients.

What evidence suggests that tipifarnib might be an effective treatment for advanced cancer?

Research has shown that tipifarnib, the treatment under study in this trial, may help treat certain cancers with HRAS mutations. For patients with head and neck cancer, those taking tipifarnib lived an average of 5.6 months without disease progression, compared to 3.6 months with previous treatments. In another study, about 31% of patients with relapsed or aggressive lymphoma experienced some reduction in their cancer. Tipifarnib blocks the growth of cancer cells with specific changes in the HRAS gene, suggesting it could be effective for tumors with these genetic changes. ^{2 4 6 7 8}

Who Is on the Research Team?

Christine A Pratilas

Principal Investigator

Children's Oncology Group

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: Treatment (tipifarnib) Experimental Treatment 1 Intervention

Patients receive tipifarnib tablets 350 mg/m\^2/dose PO or via nasogastric or gastric tube BID (maximum 600 mg/dose BID) with food 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.

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+

Published Research Related to This Trial

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33750196/

Tipifarnib in Head and Neck Squamous Cell Carcinoma With ... Median progression-free survival on tipifarnib was 5.6 months (95% CI, 3.6 to 16.4) versus 3.6 months (95% CI, 1.3 to 5.2) on last prior therapy ...

2. cancernetwork.com cancernetwork.com/view/tipifarnib-produced-positive-efficacy-data-for-treatment-of-hnscc-with-hras-mutations

Tipifarnib Produced Positive Efficacy Data for Treatment of ... For median progression-free survival (PFS), that number was 5.6 months (95% CI, 3.6-16.4) for patients who received tipifarnib compared with 3.6 ...

3. ir.kuraoncology.com ir.kuraoncology.com/news-releases/news-release-details/kura-oncology-reports-overall-survival-data-phase-2-trial

Kura Oncology Reports Overall Survival Data from Phase 2 ... Outcomes with approved therapies are poor, with reported median OS of 5-8 months, PFS of 2-3 months and ORR of 13-16% in the second line.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03719690

NCT03719690 | Safety and Efficacy of Tipifarnib in Head ... An international, multicenter, open-label, 2 cohort, non-comparative, pivotal study evaluating the efficacy of tipifarnib in HRAS mutant HNSCC (AIM-HN).

5. ashpublications.org ashpublications.org/bloodadvances/article/8/17/4581/516944/Phase-2-trial-of-the-farnesyltransferase-inhibitor

Phase 2 trial of the farnesyltransferase inhibitor tipifarnib for ... A prior phase 2 trial of tipifarnib in patients with relapsed/refractory aggressive lymphoma reported a 31% (11/36) overall response rate in the ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2000631/

Exposure-toxicity relationships for tipifarnib in cancer patients Several clinical studies have shown that the toxicity of tipifarnib in cancer patients is acceptable. However, previous exposure vs. toxicity analyses have ...

7. ir.kuraoncology.com ir.kuraoncology.com/news-releases/news-release-details/kura-oncology-provides-update-phase-2-trial-tipifarnib-hras

Kura Oncology Provides Update on Phase 2 Trial of ... In extensive clinical trials, tipifarnib has shown a well-established safety profile and compelling and durable anti-cancer activity in certain patient subsets.

8. annalsofoncology.org annalsofoncology.org/article/S0923-7534(23)04185-6/fulltext

LBA47 A phase II study evaluating tipifarnib in mHRAS ... Conclusions. Tipifarnib was safe and tolerable with anti-tumor activity observed in mHRAS R/M HNSCC pts post-IO and as later-line therapy.