Onalespib + CDKI AT7519 for Advanced Cancer

No longer recruiting at 6 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: Steroids, Anti-epileptics, Antiretrovirals

Disqualifiers: Brain metastases, Cardiac arrhythmia, others

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

Compensation: Varies

Number of Visits: 4

Duration: 21 days per cycle

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial seeks to determine the safest dose and observe the side effects of two drugs, onalespib and CDKI AT7519 (an enzyme inhibitor), for treating advanced solid tumors that cannot be surgically removed. These drugs may halt tumor growth by blocking enzymes essential for cancer cell growth. The trial seeks participants with solid tumors that have spread or are inoperable, particularly if other treatments have failed. Participants should not have undergone recent chemotherapy or radiation and must adhere to study guidelines. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this new treatment.

Do I have to stop taking my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. However, you cannot participate if you have had chemotherapy or radiotherapy within the last 3 weeks, or if you are on certain investigational drugs or antiretroviral therapy that interacts with specific enzymes. It's best to discuss your current medications with the trial team.

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

Research shows that the combination of onalespib and CDKI AT7519 has been tested for treating advanced solid tumors. Studies have found that most patients tolerate this treatment well. While some side effects may occur, they are usually manageable. Earlier trials showed encouraging results, indicating that the treatment can be effective and safe for most people. This suggests that, although side effects can occur, they are not severe for most participants. Overall, the evidence suggests it is a safe option for further study in clinical trials. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Onalespib and CDKI AT7519 for advanced cancer because it targets cancer cells in a novel way. Unlike traditional treatments that often focus solely on inhibiting the rapid division of cancer cells, Onalespib works by inhibiting a protein called HSP90, which helps stabilize many proteins required for tumor growth. CDKI AT7519 complements this by blocking specific enzymes called cyclin-dependent kinases (CDKs) that are also crucial for cell division. Together, these treatments aim to disrupt multiple pathways cancer cells use to survive and proliferate, potentially offering a more comprehensive approach to stopping tumor growth.

What evidence suggests that this trial's treatments could be effective for advanced cancer?

Research has shown that the combination of onalespib and CDKI AT7519, which participants in this trial will receive, may help treat advanced solid tumors. Onalespib blocks HSP90, a protein that aids cancer cell survival. CDKI AT7519 targets cyclin-dependent kinases, enzymes that assist in cell division. Early results suggest this combination can halt tumor growth by blocking these crucial pathways. Studies have found this treatment tolerable, with some early signs of effectiveness in controlling cancer progression. ^{1 2 3 4 6}

Who Is on the Research Team?

Khanh T Do

Principal Investigator

Dana-Farber - Harvard Cancer Center LAO

Are You a Good Fit for This Trial?

This trial is for adults with solid tumors that have spread or can't be surgically removed, and who've recovered from previous treatments (except hair loss). They should not be pregnant, must use birth control, and have a life expectancy over 3 months. Participants need normal organ function tests and measurable disease by certain medical imaging standards.

Inclusion Criteria

My cancer can be measured or evaluated using specific criteria.

My kidney function is within the normal range.

Contraception and pregnancy requirements: Women of childbearing potential and male patients with partners of childbearing potential must agree to use adequate contraception, breastfeeding should be discontinued while the mother is treated with onalespib and AT7519M

Exclusion Criteria

I have brain metastases or carcinomatous meningitis but meet certain conditions.

Patients who are receiving any other investigational agents

History of allergic reactions attributed to compounds of similar chemical or biologic composition to onalespib or AT7519M

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive onalespib IV over 1 hour on days 1 and 4 (cycle 0 only), then onalespib IV and CDKI AT7519 IV over 1 hour on days 1, 4, 8, and 11 (cycle 1 and subsequent cycles). Cycles repeat every 21 days.

21 days per cycle

4 visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days

What Are the Treatments Tested in This Trial?

Interventions

• CDKI AT7519
• Onalespib

Trial Overview The study is testing the safety and optimal dosages of two drugs, Onalespib and CDKI AT7519, in patients with advanced solid tumors. These drugs are believed to inhibit enzymes necessary for tumor cell growth. The trial will also analyze biomarkers in the lab to understand how these drugs work.

How Is the Trial Designed?

Group I: Treatment (onalespib, CDKI AT7519) Experimental Treatment 4 Interventions

Patients receive onalespib IV over 1 hour on days 1 and 4 (cycle 0 only). Patients then receive onalespib IV over 1 hour and CDKI AT7519 IV over 1 hour on days 1, 4, 8, and 11 (cycle 1 and subsequent cycles thereafter). Cycles repeat every 21 days (7 days for course 0 only) 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+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7954579/

Phase 1 study of the HSP90 inhibitor onalespib in ... We conducted a phase 1 trial of the HSP90 inhibitor onalespib in combination with the CDK inhibitor AT7519, in patients with advanced solid tumors.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02503709

Onalespib and CDKI AT7519 in Treating Patients With ... This phase I trial studies the side effects and best dose of onalespib and CDKI AT7519 in treating patients with solid tumors that have spread from the ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1355814524000774

An update on the status of HSP90 inhibitors in cancer ... This study concluded that the combination of onalespib and AT7519 was tolerable with promising preliminary activity. A combination of onalespib with erlotinib, ...

4. dana-farber.org dana-farber.org/clinical-trials/16-711

A Phase I Trial of the Combination of the Heat Shock ... This phase I trial studies the side effects and best dose of onalespib and CDKI AT7519 in treating patients with solid tumors that have spread from the ...

5. researchgate.net researchgate.net/publication/346029330_Phase_1_study_of_the_HSP90_inhibitor_onalespib_in_combination_with_AT7519_a_pan-CDK_inhibitor_in_patients_with_advanced_solid_tumors

Phase 1 study of the HSP90 inhibitor onalespib in ... Purpose We conducted a phase 1 trial of the HSP90 inhibitor onalespib in combination with the CDK inhibitor AT7519, in patients with advanced solid tumors to ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33095286/

Phase 1 study of the HSP90 inhibitor onalespib in ... - PubMed Combined onalespib and AT7519 is tolerable, though below monotherapy RP2D. Promising preliminary clinical activity was seen.