Cabozantinib + Pamiparib for Advanced Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Must not be taking: CYP3A inhibitors, Herbal medications

Disqualifiers: Uncontrolled hypertension, Recent stroke, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 6 months

44 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing cabozantinib and pamiparib in patients with advanced or treatment-resistant solid tumors. The goal is to find the best dose and understand the side effects. These drugs work by blocking enzymes that cancer cells need to grow.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot take certain drugs that affect liver enzymes (CYP3A inhibitors or inducers) or herbal supplements during the study. It's best to discuss your current medications with the study team.

What data supports the effectiveness of the drugs Cabozantinib and Pamiparib for advanced cancer?

Pamiparib has shown antitumor activity and safety in patients with advanced solid tumors and ovarian cancer, suggesting it may be effective in treating other advanced cancers. Additionally, combining pamiparib with other treatments has shown promise in enhancing antitumor effects. ^{1 2 3 4 5}

Is the combination of Cabozantinib and Pamiparib safe for humans?

Pamiparib has been studied in various cancers and generally shows an acceptable safety profile, meaning it is considered safe enough for use in humans. However, specific safety data for the combination of Cabozantinib and Pamiparib is not provided in the available research. ^{1 2 3 4 6}

How is the drug combination of Cabozantinib and Pamiparib unique for treating advanced cancer?

The combination of Cabozantinib and Pamiparib is unique because it pairs a tyrosine kinase inhibitor (Cabozantinib) with a PARP inhibitor (Pamiparib), potentially offering a novel approach by targeting cancer growth and DNA repair mechanisms simultaneously, which is different from standard treatments that typically focus on one pathway. ^{1 2 3 4 6}

Research Team

Siqing FU, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

Adults with advanced solid tumors that are resistant to standard treatments or have no standard treatment options available. Participants must have specific genetic markers related to tumor growth, be able to take oral medication, and not have had certain recent treatments. They should also meet various health criteria like adequate blood cell counts and organ function, agree to use effective contraception, and not be pregnant or breastfeeding.

Inclusion Criteria

My condition has a specific genetic feature confirmed by a certified lab.

I can take pills and do not have chronic stomach or absorption problems.

I am fully active or restricted in physically strenuous activity but can do light work.

Exclusion Criteria

Pregnancy or breastfeeding

I have not received a live vaccine recently.

I am currently taking blood thinners.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive cabozantinib orally once daily and pamiparib orally twice daily. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Up to 6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Treatment Details

Interventions

• Cabozantinib
• Pamiparib

Trial Overview The trial is testing the combination of two drugs, Cabozantinib and Pamiparib, for their effectiveness in stopping tumor growth by inhibiting enzymes needed for cell proliferation. It aims to determine the optimal dosages and document any side effects when used together on patients with refractory advanced solid tumors.

Participant Groups

Group I: Treatment (cabozantinib, pamiparib) Experimental Treatment 2 Interventions

Patients receive cabozantinib PO QD and pamiparib PO BID. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cabozantinib is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Cabometyx for:

• Renal cell carcinoma
• Hepatocellular carcinoma

Approved in United States as Cabometyx for:

• Renal cell carcinoma
• Hepatocellular carcinoma

Approved in Canada as Cabometyx for:

• Renal cell carcinoma
• Hepatocellular carcinoma

Approved in Japan as Cabometyx for:

• Renal cell carcinoma

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Findings from Research

Pamiparib demonstrated promising efficacy in treating locally advanced or metastatic HER2-negative breast cancer with deleterious or suspected deleterious BRCA1/2 mutations, achieving an objective response rate of 38.2% in triple-negative breast cancer and 61.9% in hormone receptor-positive cohorts.

The treatment was generally well-tolerated, although hematologic adverse events were common, leading to dose reductions in 64.8% of patients, indicating a need for monitoring but an overall acceptable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pamiparib in patients with locally advanced or metastatic HER2-negative breast cancer with germline BRCA mutations: a phase II study. Xu, B., Sun, T., Shi, Y., et al.[2023]

The combination of pamiparib (a PARP inhibitor) and tislelizumab (an anti-PD-1 antibody) was generally well tolerated in a study of 49 patients with advanced solid tumors, with a recommended phase 2 dose established as tislelizumab 200 mg every 3 weeks plus pamiparib 40 mg twice daily.

Out of the participants, 20% achieved an objective response, including two complete responses, indicating that this combination therapy may provide clinical benefits and warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pamiparib in combination with tislelizumab in patients with advanced solid tumours: results from the dose-escalation stage of a multicentre, open-label, phase 1a/b trial. Friedlander, M., Meniawy, T., Markman, B., et al.[2020]

In a study involving 180 patients with advanced solid tumors, the combination of pamiparib and tislelizumab demonstrated an overall objective response rate (ORR) of 20%, with the highest response (47.4%) observed in patients with triple-negative breast cancer (TNBC) who had BRCA1/2 mutations or homologous recombination deficiency.

While the treatment showed promising antitumor activity, it was associated with a significant incidence of treatment-emergent adverse events, with 61.7% of patients experiencing grade 3 or higher side effects, indicating that while the therapy is effective, careful monitoring for safety is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pamiparib in combination with tislelizumab in patients with advanced solid tumours: results from the dose-expansion stage of a multicentre, open-label, phase I trial. Friedlander, M., Mileshkin, L., Lombard, J., et al.[2023]

Pamiparib, administered at 60 mg twice a day, demonstrated significant antitumor activity in patients with advanced ovarian cancer, achieving an objective response rate of 64.6% in those with platinum-sensitive ovarian cancer (PSOC) and 31.6% in platinum-resistant ovarian cancer (PROC).

The treatment was well-tolerated, with a manageable safety profile, although some patients experienced grade ≥3 adverse events, primarily hematologic toxicities like anemia and decreased neutrophil count.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pamiparib Monotherapy for Patients with Germline BRCA1/2-Mutated Ovarian Cancer Previously Treated with at Least Two Lines of Chemotherapy: A Multicenter, Open-Label, Phase II Study. Wu, X., Zhu, J., Wang, J., et al.[2023]

The combination of the AKT inhibitor ipatasertib with paclitaxel significantly improved progression-free survival in patients with metastatic triple-negative breast cancer, especially in those with specific genetic alterations (PIK3CA/AKT1/PTEN).

Circulating tumor DNA (ctDNA) analysis showed that lower levels of ctDNA during treatment were associated with better outcomes, indicating that ctDNA could be a useful tool for monitoring treatment response and prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Circulating Tumor DNA and Biomarker Analyses From the LOTUS Randomized Trial of First-Line Ipatasertib and Paclitaxel for Metastatic Triple-Negative Breast Cancer. Wongchenko, MJ., Kim, SB., Saura, C., et al.[2022]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Pamiparib in patients with locally advanced or metastatic HER2-negative breast cancer with germline BRCA mutations: a phase II study. [2023]

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

Pamiparib in combination with tislelizumab in patients with advanced solid tumours: results from the dose-escalation stage of a multicentre, open-label, phase 1a/b trial. [2020]

3. England pubmed.ncbi.nlm.nih.gov

Pamiparib in combination with tislelizumab in patients with advanced solid tumours: results from the dose-expansion stage of a multicentre, open-label, phase I trial. [2023]

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

Pamiparib Monotherapy for Patients with Germline BRCA1/2-Mutated Ovarian Cancer Previously Treated with at Least Two Lines of Chemotherapy: A Multicenter, Open-Label, Phase II Study. [2023]

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

Circulating Tumor DNA and Biomarker Analyses From the LOTUS Randomized Trial of First-Line Ipatasertib and Paclitaxel for Metastatic Triple-Negative Breast Cancer. [2022]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Pamiparib: First Approval. [2021]