Niraparib + Panitumumab for Colorectal Cancer

(NIPAVect Trial)

Recruiting at 2 trial locations

Overseen By Olatunji Alese, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Emory University

Must not be taking: PARP inhibitors, EGFR inhibitors

Disqualifiers: Interstitial pneumonitis, Pulmonary fibrosis, HIV, 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

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

Compensation: Varies

Number of Visits: 3

Duration: 28 days per cycle

26 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it does mention that you cannot be enrolled in another interventional clinical trial and should not have prior therapy with certain inhibitors. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug combination Niraparib and Panitumumab for colorectal cancer?

Panitumumab has been shown to help some patients with metastatic colorectal cancer live longer without their disease getting worse, especially when their tumors have certain genetic features. However, combining panitumumab with other treatments has sometimes led to more side effects and hasn't always improved outcomes. ^{1 2 3 4 5}

Is the combination of Niraparib and Panitumumab safe for treating colorectal cancer?

Panitumumab, when used with other treatments for colorectal cancer, has been associated with serious side effects like skin rash, diarrhea, and low magnesium levels, and in some cases, increased risk of death. It is important to discuss potential risks with your doctor. ^{1 2 3 5 6}

How is the drug combination of Niraparib and Panitumumab unique for treating colorectal cancer?

The combination of Niraparib and Panitumumab for colorectal cancer is unique because it pairs a PARP inhibitor (Niraparib) with an EGFR inhibitor (Panitumumab), potentially offering a novel approach by targeting different pathways involved in cancer growth, which is not a standard treatment for this condition. ^{1 2 3 7 8}

What is the purpose of this trial?

This trial studies how well niraparib and panitumumab work together in treating patients with advanced colorectal cancer who have already received treatment. Niraparib blocks enzymes needed for cancer growth, while panitumumab helps the immune system attack cancer cells and stops them from spreading. Panitumumab is a fully human monoclonal antibody that targets the epidermal growth factor receptor (EGFR) and is used in the treatment of metastatic colorectal cancer, particularly in patients with wild-type KRAS tumors.

Research Team

Olatunji Alese, MD

Principal Investigator

Emory University

Eligibility Criteria

This trial is for adults with advanced colorectal cancer that has spread, who have tried at least one systemic therapy. They must be in good physical condition (ECOG ≤ 1), have adequate blood counts and organ function, and not be pregnant or fathering a child. Those with prior treatment using PARP or EGFR inhibitors, active brain metastases, known hypersensitivity to the drugs being tested, or other serious health issues are excluded.

Inclusion Criteria

I've had chemotherapy before and either it didn't work, I couldn't tolerate it, or I'm currently on a stable first line treatment.

I am fully active and can carry on all pre-disease activities without restriction.

I agree to use birth control from the start of the study until 6 months after it ends.

Exclusion Criteria

I do not have active brain or spinal cord cancer symptoms.

Participant must not be simultaneously enrolled in any interventional clinical trial

I haven't had significant radiation therapy affecting my bone marrow recently.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive niraparib orally once daily and panitumumab intravenously on days 1 and 15, with cycles repeating every 28 days

28 days per cycle

2 visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

Up to 5 years

1 visit at 30 days, then every 6 months for 2 years, and annually thereafter

Treatment Details

Interventions

• Niraparib
• Panitumumab

Trial Overview The trial is testing the combination of niraparib (an enzyme inhibitor) and panitumumab (a monoclonal antibody immunotherapy) on patients with RAS wildtype colorectal cancer. The goal is to see if this drug duo can better halt tumor growth compared to current treatments.

Participant Groups

Group I: Treatment (niraparib, panitumumab) Experimental Treatment 2 Interventions

Patients receive 200 or 300 mg niraparib orally once daily on days 1-28 and 6 mg/kg panitumumab intravenously over 60-90 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

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

Approved in European Union as Zejula for:

• Maintenance treatment of adults with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete or partial) following completion of first-line platinum-based chemotherapy
• Maintenance treatment of adults with platinum-sensitive relapsed high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete or partial) to platinum-based chemotherapy

Approved in United States as Zejula for:

• Maintenance treatment of adults with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy
• Treatment of adults with advanced ovarian, fallopian tube, or primary peritoneal cancer treated with three or more prior chemotherapy regimens and whose cancer is associated with homologous recombination deficiency (HRD)-positive status

Approved in Canada as Zejula for:

• Maintenance treatment of adults with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

GlaxoSmithKline

Industry Sponsor

Trials

4,834

Recruited

8,389,000+

Headquarters

London, UK

Known For

Vaccines & Medicines

Top Products

**Advair (salmeterol, fluticasone propionate)**, **Shingrix (shingles vaccine)**, **Augmentin (amoxicillin/clavulanate potassium)**, **Ventolin (salbutamol sulfate)

Dame Emma Walmsley

GlaxoSmithKline

Chief Executive Officer since 2017

MA in Classics and Modern Languages from Oxford University

Dr. Hal Barron

GlaxoSmithKline

Chief Medical Officer since 2018

MD from Harvard Medical School

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

A clinical trial showed that adding panitumumab to bevacizumab and chemotherapy for first-line treatment of metastatic colorectal cancer resulted in worse progression-free survival and increased toxicity compared to bevacizumab and chemotherapy alone.

Patients receiving panitumumab experienced a higher incidence of severe adverse events (87% vs. 72%) and a greater risk of death (9% vs. 4%), leading to the conclusion that panitumumab should not be recommended in this treatment setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA review of a panitumumab (Vectibix) clinical trial for first-line treatment of metastatic colorectal cancer. Giusti, RM., Cohen, MH., Keegan, P., et al.[2018]

Panitumumab (Vectibix) was evaluated in a trial with 463 patients suffering from advanced colorectal cancer, showing a mean progression-free survival (PFS) of 96 days compared to 60 days for those receiving only best supportive care, indicating a significant benefit in delaying disease progression.

Despite the improvement in PFS and an objective response rate of 8%, there was no difference in overall survival between the treatment groups, leading to accelerated approval by the FDA with the requirement for further confirmation of clinical benefit for full approval.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

U.S. Food and Drug Administration approval: panitumumab for epidermal growth factor receptor-expressing metastatic colorectal carcinoma with progression following fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens. Giusti, RM., Shastri, K., Pilaro, AM., et al.[2020]

Panitumumab (Vectibix) is approved for treating metastatic colorectal cancer specifically in patients with EGFR-expressing tumors that have non-mutated K-ras genes after standard chemotherapy has failed.

In a phase III study, patients receiving panitumumab along with best supportive care experienced significantly longer progression-free survival compared to those who only received best supportive care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Panitumumab]. Musch, A.[2018]

A personalized treatment approach using the combination of vemurafenib and panitumumab was successfully implemented in a metastatic colorectal cancer patient with a specific genetic profile, leading to strong disease control.

This combination therapy was well tolerated, showing no typical side effects associated with vemurafenib, suggesting it may be a safer option for patients who have progressed on standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vemurafenib and panitumumab combination tailored therapy in BRAF-mutated metastatic colorectal cancer: a case report. Capalbo, C., Marchetti, P., Coppa, A., et al.[2021]

Panitumumab, approved for treating metastatic colorectal cancer, significantly improved progression-free survival (PFS) compared to best supportive care alone, with median PFS times of 56 days versus 51 days, respectively, in a study of 463 patients.

While panitumumab showed efficacy in delaying disease progression, it did not improve overall survival, and common side effects included skin rash and hypomagnesemia, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA drug approval summary: panitumumab (Vectibix). Giusti, RM., Shastri, KA., Cohen, MH., et al.[2018]

In a phase 2 study involving 148 patients with metastatic colorectal cancer, panitumumab demonstrated a 9% overall response rate and a median progression-free survival of 14 weeks, indicating its efficacy as a treatment option for patients who had previously failed other therapies.

Panitumumab was generally well tolerated, with manageable side effects; 95% of patients experienced skin toxicity, but only 5% had severe reactions, suggesting that while dermatologic issues are common, they are not typically severe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Panitumumab monotherapy in patients with previously treated metastatic colorectal cancer. Hecht, JR., Patnaik, A., Berlin, J., et al.[2018]

Panitumumab, an anti-EGFR monoclonal antibody, significantly improves progression-free survival when combined with chemotherapy in patients with wild-type KRAS metastatic colorectal cancer, but shows no overall survival benefit in second-line treatment.

In patients with mutant KRAS tumors, panitumumab is less effective, leading to shorter progression-free survival when combined with certain chemotherapy regimens, highlighting the importance of KRAS mutation status in treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spotlight on panitumumab in metastatic colorectal cancer. Keating, GM.[2018]

Panitumumab, when combined with chemotherapy, significantly prolongs progression-free survival in patients with wild-type KRAS metastatic colorectal cancer, but shows no overall survival benefit in second-line treatment.

In patients with mutant KRAS tumors, panitumumab is less effective, leading to shorter progression-free survival compared to chemotherapy alone, highlighting the importance of KRAS mutation status in treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Panitumumab: a review of its use in metastatic colorectal cancer. Keating, GM.[2021]

References

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

FDA review of a panitumumab (Vectibix) clinical trial for first-line treatment of metastatic colorectal cancer. [2018]

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

U.S. Food and Drug Administration approval: panitumumab for epidermal growth factor receptor-expressing metastatic colorectal carcinoma with progression following fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens. [2020]

3. Germany pubmed.ncbi.nlm.nih.gov

[Panitumumab]. [2018]

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

Vemurafenib and panitumumab combination tailored therapy in BRAF-mutated metastatic colorectal cancer: a case report. [2021]

5. England pubmed.ncbi.nlm.nih.gov

FDA drug approval summary: panitumumab (Vectibix). [2018]

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

Panitumumab monotherapy in patients with previously treated metastatic colorectal cancer. [2018]

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

Spotlight on panitumumab in metastatic colorectal cancer. [2018]

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

Panitumumab: a review of its use in metastatic colorectal cancer. [2021]