RiMO-301 + Radiotherapy for Head and Neck Cancer

Overseen By Ze-Qi Xu

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Coordination Pharmaceuticals, Inc.

Must be taking: PD-1 inhibitors

Must not be taking: Anti-neoplastic agents

Disqualifiers: End organ failure, CNS metastases, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

16 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called RiMO-301 for individuals with hard-to-treat head and neck cancer. It combines RiMO-301 with radiation therapy and a PD-1 inhibitor (a type of cancer drug) to determine if this combination can effectively target tumors. The trial targets individuals whose cancer has returned or spread and cannot be surgically removed. Participants should have a noticeable tumor that can be injected with RiMO-301 and are either currently treated with PD-1 inhibitors or suitable for this treatment. Those with a history of head and neck cancer requiring palliative radiotherapy, who have not responded to or cannot tolerate standard chemotherapy, might be a good fit. As a Phase 1 trial, this research focuses on understanding how RiMO-301 works in people, offering participants a chance to be among the first to receive this new treatment.

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

The trial does not specify if you need to stop taking your current medications, but it does require that you have not received any anti-cancer treatments other than PD-1 inhibitors within 4 weeks before starting the trial.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that RiMO-301, when combined with radiation therapy and a PD-1 inhibitor, is generally well-tolerated. In a previous study, patients with advanced tumors received RiMO-301, sometimes with a PD-1 inhibitor. The treatment showed promising results and was well-tolerated, with most participants not experiencing serious side effects.

The current study is in its early stages, focusing on safety and determining the right dose. While this doesn't guarantee complete safety, earlier studies have indicated that RiMO-301 has been safe enough to warrant further testing.

It is important to discuss any concerns with a healthcare provider before joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about RiMO-301 because it introduces a novel approach to treating head and neck cancer. Unlike traditional treatments like chemotherapy and surgery, RiMO-301 involves an intratumoral injection that works by enhancing the effects of radiation therapy. This treatment leverages nanoparticles to amplify the radiation's impact directly within the tumor, potentially increasing effectiveness while minimizing damage to surrounding healthy tissues. Additionally, combining RiMO-301 with immune checkpoint inhibitors like pembrolizumab or nivolumab may boost the immune system's ability to attack cancer cells, offering a promising new strategy for tackling this challenging condition.

What evidence suggests that RiMO-301 might be an effective treatment for head and neck cancer?

Research shows that RiMO-301 is a promising new treatment for head and neck cancer. It uses tiny particles to enhance radiation therapy, allowing the radiation to more effectively target and shrink tumors. In this trial, participants will receive an intratumoral injection of RiMO-301 followed by either pembrolizumab or nivolumab, both PD-1 inhibitors, and then hypofractionated radiation. Studies have found that RiMO-301, when combined with a PD-1 inhibitor, was well tolerated and showed early signs of success in treating advanced tumors. This combination of RiMO-301 with radiation and immune therapy has led to better results for patients, offering hope for those with difficult-to-treat cancers. ^{3 5 6 7 8}

Who Is on the Research Team?

Lawrence E. Feldman

Principal Investigator

University of Illinois at Chicago

Are You a Good Fit for This Trial?

This trial is for adults with head-neck cancer that's inoperable, recurrent, or has spread. They should have a lesion suitable for RiMO-301 injection and radiation therapy, not previously treated by radiation or at least six months post-radiation without complications. Participants need to be recovering from prior treatments' effects, have good organ function, an expected lifespan of 12+ weeks, and can be on standard PD-1 inhibitors like pembrolizumab or nivolumab.

Inclusion Criteria

My bone marrow and liver are functioning well.

I am able to get out of my bed or chair and move around.

I have head and neck cancer that cannot be removed by surgery and qualifies for PD-1 inhibitor treatment.

Exclusion Criteria

I have symptoms from cancer spread to my brain or its coverings.

I do not have severe chronic illnesses or conditions affecting my organs.

I have a serious infection at or near my cancer site.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intratumoral injection of RiMO-301 followed by pembrolizumab or nivolumab and hypofractionated radiation

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Long-term Follow-up

Participants are monitored for overall survival

24 months

What Are the Treatments Tested in This Trial?

Interventions

• RiMO-301

Trial Overview The study tests RiMO-301 combined with hypofractionated radiotherapy and a PD-1 inhibitor (pembrolizumab/nivolumab) in patients with advanced head-neck cancer. It's an open-label (everyone knows the treatment), single-arm (one treatment group), non-randomized trial focusing on those who may benefit from palliative radiotherapy.

How Is the Trial Designed?

Group I: RiMO-301 Experimental Treatment 1 Intervention

Intratumoral injection of RiMO-301 followed by pembrolizumab or nivolumab followed by hypofractionated radiation

Who Is Running the Clinical Trial?

Coordination Pharmaceuticals, Inc.

Lead Sponsor

Trials

6

Recruited

130+

University of Illinois at Chicago

Collaborator

Trials

653

Recruited

1,574,000+

Published Research Related to This Trial

In a phase II trial involving 32 patients with advanced head and neck cancer, the aggressive combination of cisplatinum and paclitaxel with hyperfractionated-accelerated radiotherapy resulted in a 5-year overall survival rate of 48% and a disease-free survival rate of 43%.

While the treatment showed promising response rates, with 69% achieving a complete response, it was associated with significant acute toxicities, including high rates of grade 3 mucositis (71%) and erythema (28%), indicating the need for extensive supportive care during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of a simultaneous radiochemotherapy with cisplatinum and paclitaxel in combination with hyperfractionated-accelerated radiotherapy in locally advanced head and neck tumors. Kuhnt, T., Becker, A., Bloching, M., et al.[2022]

Intensity-modulated radiotherapy (IMRT) for oropharyngeal squamous cell carcinoma showed promising 5-year local control rates, with 87% overall and varying by cancer stage, indicating its efficacy in managing advanced disease.

The treatment resulted in a 5-year cause-specific survival rate of 85% and an overall survival rate of 76%, with a relatively low incidence of severe late complications (8%), suggesting that IMRT is a safe and effective option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensity-modulated radiotherapy for oropharyngeal squamous cell carcinoma. Mendenhall, WM., Amdur, RJ., Morris, CG., et al.[2022]

A new anthropomorphic phantom for head and neck cancer treatment was successfully designed to verify the quality of intensity-modulated proton therapy, ensuring accurate dose delivery for clinical trials.

The phantom's dosimetry results showed that the measured doses were very close to the calculated doses, with all trials meeting the acceptance criteria, indicating that the phantom can effectively be used for quality assurance in proton therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Anthropomorphic Head and Neck Quality Assurance Phantom for Credentialing of Intensity-Modulated Proton Therapy. Branco, D., Taylor, P., Zhang, X., et al.[2022]

In a study of 100 patients treated with intensity-modulated radiotherapy (IMRT) for head and neck cancer, the 3-year overall survival rate was 71%, indicating that IMRT is an effective treatment option.

While IMRT showed promising outcomes, there were cases of local failure at the edges of high-dose areas, suggesting that careful planning is crucial to avoid recurrence in these regions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patterns of failure and toxicity after intensity-modulated radiotherapy for head and neck cancer. Schoenfeld, GO., Amdur, RJ., Morris, CG., et al.[2022]

The Radiation Therapy Oncology Group (RTOG) has established that postoperative radiotherapy significantly improves local-regional control in advanced operable head and neck cancers compared to preoperative radiotherapy, setting a standard treatment protocol.

RTOG's research has also shown the efficacy of concurrent high-dose cisplatin with radiotherapy for advanced disease, leading to further Phase III trials, while identifying prognostic indicators and the need for chemoprevention strategies due to the risk of second malignancies in patients cured by radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evolution of the Radiation Therapy Oncology Group clinical trials for head and neck cancer. Fu, KK., Cooper, JS., Marcial, VA., et al.[2019]

In a study of 18 patients with head and neck cancer treated with intensity-modulated radiotherapy (IMRT), a high overall response rate was observed, with 71.4% achieving a complete or partial response at 3 months, increasing to 89% at a median follow-up of 5.6 months.

Concurrent chemotherapy with IMRT was well-tolerated, with no distant metastasis reported, suggesting that this treatment combination may be effective and safe for patients with locoregionally advanced head and neck cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensity-modulated radiation therapy in head-and-neck cancer, first report in Thailand. Lertbutsayanukul, C., Khorprasert, C., Shotelersuk, K., et al.[2016]

A study of 203 patients with head and neck carcinoma of unknown primary (HNCUP) treated with intensity-modulated radiation therapy (IMRT) showed a high overall survival rate of 79% over a median follow-up of 5 years, indicating effective tumor control.

The approach of risk-adaptive radiation volume de-escalation resulted in low rates of local (3%) and regional failure (14%), with only 7% experiencing grade ≥3 late toxicity, suggesting that this method is both effective and safe for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of risk-tailored individualized selection of radiation therapy target volume for head and neck carcinoma of unknown primary. Ghatasheh, H., Huang, SH., Su, J., et al.[2022]

In a study of 41 patients with locally-advanced stage IV head and neck cancer, intensity-modulated radiotherapy with simultaneous integrated boost (SIB-IMRT) demonstrated a high overall response rate of 84.2%, indicating its efficacy in treating this cancer type.

SIB-IMRT was found to be safe, with manageable acute toxicities, and showed similar local control and overall survival rates whether used alone or in combination with chemotherapy or cetuximab, making it a viable option for patients who cannot tolerate systemic therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Simultaneous Integrated Boost Radiotherapy in Unresectable Stage IV (M0) Head and Neck Squamous Cell Cancer Patients: Daily Clinical Practice. Iatì, G., Parisi, S., Santacaterina, A., et al.[2022]

The JAVELIN Head and Neck 100 study is a Phase III clinical trial investigating the effectiveness of avelumab, a PD-L1 inhibitor, combined with standard chemoradiotherapy (CRT) for high-risk, locoregionally advanced squamous cell carcinomas of the head and neck.

This study addresses a critical gap in research, as there are currently no prospective studies evaluating immune checkpoint inhibitors in the definitive treatment of nonmetastatic HNSCC, which is important for improving outcomes in patients with poor prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

JAVELIN Head and Neck 100: a Phase III trial of avelumab and chemoradiation for locally advanced head and neck cancer. Yu, Y., Lee, NY.[2020]

In a study of 61 patients undergoing proton reirradiation for head and neck cancers, the treatment showed reasonable survival outcomes with a median overall survival of 16.5 months and a 2-year overall survival estimate of 32.7%.

While proton therapy provided effective locoregional disease control, it was associated with significant toxicities, with 14.7% experiencing severe acute side effects and 24.6% facing late toxicities, including 3 treatment-related deaths.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reirradiation of Recurrent and Second Primary Head and Neck Cancer With Proton Therapy. McDonald, MW., Zolali-Meybodi, O., Lehnert, SJ., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05838729

Study of RiMO-301 and Radiotherapy With PD-1 Inhibitor ... To determine overall survival for up to 24 months; To assess patient quality of life. The target population is patients with unresectable, recurrent or ...

2. withpower.com withpower.com/trial/phase-2-head-and-neck-neoplasms-3-2023-31d9c

RiMO-301 + Radiotherapy for Head and Neck Cancer RiMO-301 is a novel treatment that enhances the effects of radiotherapy by using nanoparticles to improve the delivery and effectiveness of radiation in ...

3. researchgate.net researchgate.net/publication/371303941_A_phase_1_dose-escalation_study_of_RiMO-301_with_palliative_radiation_in_advanced_tumors

A phase 1 dose-escalation study of RiMO-301 with ... Conclusions: RiMO-301 with or without pembrolizumab was well tolerated and demonstrated promising signs of efficacy in patients with advanced ...

4. synapse.patsnap.com synapse.patsnap.com/drug/c9eb855b691443fc96c8299784baafec

RiMO-301 - Drug Targets, Indications, Patents Head and neck cancer metastaticSquamous Cell Carcinoma of Head and NeckAdvanced cancer ... Clinical Results associated with RiMO-301. Login to view more ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12130423/

Radiotherapy improves the clinical outcomes of recurrent or ... The combination of immunotherapy and radiotherapy demonstrates improved clinical outcomes in R/M HNSCC.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05838729

Study of RiMO-301 and Radiotherapy With PD-1 Inhibitor ... This is a prospective, open-label, single arm, non-randomized study of RiMO-301 with hypofractionated radiation and a PD-1 Inhibitor in patients with ...

7. trialx.com trialx.com/clinical-trials/listings/219472/study-of-rimo-301-and-radiotherapy-with-pd-1-inhibitor-for-the-treatment-of-head-neck-cancer/

Study of RiMO-301 and Radiotherapy With PD-1 Inhibitor ... This is a prospective, open-label, single arm, non-randomized study of RiMO-301 with hypofractionated radiation and a PD-1 Inhibitor in patients ...

8. app.trialscreen.org app.trialscreen.org/trials/phase-1-2-head-neck-cancer-rimo-301-radiotherapy-pd-inhibitor-treatment-trial-nct05838729

Study of RiMO-301 and Radiotherapy With PD-1 Inhibitor ... This Interventional study is looking for people with Head Neck Cancer, Intratumoral Injection in Chicago United States to take part.