RiMO-301 With Radiation for Cancer

No longer recruiting at 1 trial location

Overseen By Ze-Qi Xu, Ph.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Coordination Pharmaceuticals, Inc.

Must not be taking: Chemotherapy, Targeted therapies

Disqualifiers: Lymphomas, Leukemias, Significant infection, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the optimal dose of a new treatment called RiMO-301, an experimental therapy combined with radiation, for individuals with advanced cancers. The focus is on tumors suitable for direct injection and radiation. Candidates for this trial have advanced, incurable cancer with tumors accessible for direct treatment and not previously treated with radiation. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in humans.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have had chemotherapy, targeted therapies, biologic response modifiers, or hormonal therapy in the last 14 days before starting the trial.

Is there any evidence suggesting that RiMO-301 with radiotherapy is likely to be safe for humans?

Research has shown that RiMO-301, when used with radiotherapy, is under careful study for safety. In one study where RiMO-301 was combined with pembrolizumab (a cancer treatment), two-thirds of the patients responded positively, and no serious side effects occurred. This suggests that RiMO-301 is generally well-tolerated.

Another study found that patients who received RiMO-301 with radiation had recovered from previous treatment side effects before starting this new treatment. This ensures safety by including patients who are already in stable condition.

Since RiMO-301 remains in the early testing phase (Phase 1), its safety is closely monitored. Early phase studies usually focus on finding the safest dose and checking for any side effects. So far, the data suggests that RiMO-301 is tolerated without major issues. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about RiMO-301 because it offers a unique approach to enhancing the effects of radiation therapy for cancer. Unlike traditional treatments that rely solely on radiation itself to target tumors, RiMO-301 is designed to amplify the radiation’s impact. It works by using a novel mechanism where nanoparticles increase the energy deposited in the tumor, potentially boosting the effectiveness of the radiotherapy. This could lead to more efficient tumor reduction while possibly reducing the radiation dose needed, minimizing side effects for patients.

What evidence suggests that RiMO-301 with radiation could be effective for advanced tumors?

Research has shown that RiMO-301, when combined with radiotherapy, may help treat advanced tumors. In this trial, participants will receive RiMO-301 with radiotherapy. One study demonstrated that combining RiMO-301 with pembrolizumab, a type of immunotherapy, resulted in a 66.7% overall response rate. Specifically, 4 out of 6 patients experienced a significant reduction in tumor size. The remaining patients saw a smaller decrease in tumor size, between 15% and 20%. These findings suggest that RiMO-301, especially when used with other treatments, might effectively shrink tumors. ^{1 2 3 5 6}

Are You a Good Fit for This Trial?

Adults over 18 with advanced or metastatic cancer that can't be cured, who have recovered from previous treatments and are not pregnant. The tumor must be measurable, suitable for radiotherapy, and accessible for direct injection. Patients with lymphomas/leukemias or recent therapies/surgeries are excluded.

Inclusion Criteria

Patients must sign a study-specific informed consent form prior to study entry

I have recovered from the major side effects of my previous cancer treatments.

My cancer is advanced or has spread and cannot be cured with surgery or other treatments.

Exclusion Criteria

You have a serious medical or mental health condition, or abnormal lab results that would make it unsuitable for you to participate in this study.

I haven't had chemotherapy, targeted therapies, or hormonal treatments in the last 14 days.

I am able to understand and agree to participate in the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single escalation dose of RiMO-301 intratumorally injected, followed by palliative radiation doses to determine the maximum tolerated dose (MTD)

6 weeks

Multiple visits for dose escalation and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of clinical response and adverse events

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Radiotherapy
• RiMO-301

Trial Overview The trial is testing RiMO-301 combined with radiation on patients with advanced tumors. It's an early-phase study to find the right dose of RiMO-301 when injected directly into the tumor alongside standard radiotherapy.

How Is the Trial Designed?

Group I: RiMO-301+Radiotherapy Experimental Treatment 1 Intervention

3 dose levels (5%, 10%, and 15% of the total baseline tumor volume, respectively) will be tested in a 3 + 3 dose escalation study

Who Is Running the Clinical Trial?

Coordination Pharmaceuticals, Inc.

Lead Sponsor

Trials

6

Recruited

130+

Rimo Therapeutics Inc.

Lead Sponsor

Trials

1

Recruited

20+

University of Chicago

Collaborator

Trials

1,086

Recruited

844,000+

Published Research Related to This Trial

Combining immunotherapy with radiation therapy has the potential to enhance cancer treatment outcomes, but there is a lack of laboratory data and guidance on how to effectively implement this combination.

Careful design of Phase I clinical trials is crucial due to the overlapping toxicities of both therapies, and various trial designs, such as the 3 + 3 design and continual reassessment methods, should be considered to optimize patient safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy and radiation therapy: considerations for successfully combining radiation into the paradigm of immuno-oncology drug development. Sharon, E., Polley, MY., Bernstein, MB., et al.[2021]

Intensity-modulated radiation therapy (IMRT) showed a significantly higher effective rate of 71% in treating recurrent cervical cancer compared to 39% for conventional anterior-posterior field radiotherapy, based on a study of 21 patients treated with IMRT and 18 with conventional therapy.

Patients receiving IMRT had a longer average survival time of 25 months compared to 12 months for those receiving conventional therapy, with acceptable levels of acute toxicity, indicating that IMRT is a safer and more effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Preliminary study of intensity-modulated radiation therapy for recurrent cervical cancer]. Zhou, Q., Tang, Y., Shu, XL., et al.[2008]

Intensity modulated radiation therapy (IMRT) was administered to 32 patients with cervical or endometrial cancer after surgery and chemotherapy, showing a 100% overall survival rate at one year, and 100% for preventive irradiation at two and three years.

IMRT demonstrated better dose distribution compared to traditional radiotherapy, effectively protecting surrounding organs while maintaining tolerable toxicity levels, with manageable side effects reported in a minority of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Intensity modulated radiation therapy for patients with gynecological malignancies after hysterectomy and chemotherapy/radiotherapy]. Chen, ZY., Ma, YB., Sheng, XG., et al.[2007]

Combining radiation therapy with immunotherapy shows great potential for enhancing cancer treatment, as preclinical studies suggest that radiation can make tumor cells more vulnerable to immune attacks.

Clinical trials have begun to support the idea that this combination can effectively boost antitumor immune responses, with ongoing studies exploring various therapeutic vaccines alongside radiation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combining radiation and immunotherapy for synergistic antitumor therapy. Ferrara, TA., Hodge, JW., Gulley, JL.[2021]

In a study involving 11 NSCLC patients, combining ultra-hypofractionated radiotherapy (8 Gy) with anti-PD-1 immunotherapy resulted in an impressive overall response rate of 81.8%, with 63.5% of patients experiencing significant tumor reduction (80-100%).

The treatment was well-tolerated, with negligible radiotherapy-related toxicities, although 36% of patients experienced immune-related adverse events that required interruption of immunotherapy, indicating a need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultra-Hypofractionated Re-Irradiation with Anti-PD-1 Immunotherapy for Locoregionally Recurrent (after Radical Chemo-Radiotherapy) Non-Small Cell Lung Cancer. Filippatos, K., Koukourakis, IM., Anevlavis, S., et al.[2023]

Combining immunotherapy with radiation therapy shows promising synergy in preclinical studies, as radiation can enhance the immune response against tumors by altering the tumor microenvironment and inducing immunogenic cell death.

Current clinical data indicate that this combination therapy is generally well tolerated, but further research is needed to assess both short-term and long-term risks, especially with new immunotherapy agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy and Radiation: Charting a Path Forward Together. Sridharan, V., Schoenfeld, JD.[2020]

The RTOG 3505 study is investigating the effectiveness of combining concurrent chemoradiation with the immune checkpoint inhibitor nivolumab in patients with locally advanced non-small-cell lung cancer, aiming to improve overall survival and progression-free survival.

With a planned enrollment of 660 patients, the study is designed to have sufficient power to detect significant differences in survival outcomes, ensuring robust results regarding the efficacy of nivolumab compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment Design and Rationale for a Randomized Trial of Cisplatin and Etoposide Plus Thoracic Radiotherapy Followed by Nivolumab or Placebo for Locally Advanced Non-Small-Cell Lung Cancer (RTOG 3505). Gerber, DE., Urbanic, JJ., Langer, C., et al.[2018]

Recent advancements in radiation oncology, including new technologies like proton beam therapy and the use of artificial intelligence, have the potential to improve treatment outcomes for patients with oligometastatic disease while reducing normal tissue toxicity.

A meeting organized by the European Organisation for Research and Treatment of Cancer identified key areas for future clinical trials, focusing on radiobiology-based biomarkers, combination therapies, and the integration of complex data to enhance research in radiation oncology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The European Organisation for Research and Treatment of Cancer, State of Science in radiation oncology and priorities for clinical trials meeting report. Thomas, G., Eisenhauer, E., Bristow, RG., et al.[2020]

The combination of radiotherapy and chemotherapy (RCT) has significantly improved survival outcomes for patients with inoperable stage-III non-small cell lung cancer (NSCLC), with median survival times of 15-18 months and a 5-year survival rate of 10-20%.

Concomitant RCT is more effective than sequential RCT, making it the preferred treatment approach, but there is still a need for further optimization strategies, such as induction chemotherapy, surgical options for operable tumors, and the use of biological response modifiers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stage-III NSClC: multimodality therapy for inoperable tumours. Fietkau, R.[2006]

In a phase 1 study involving 20 patients with stage IV melanoma, combining radiotherapy with nivolumab and ipilimumab was found to be safe, with treatment-related severe adverse events occurring in 40% of patients in one cohort and 30% in another, but no severe events linked to radiotherapy itself.

Patients showed positive responses to treatment outside the irradiated areas, indicating potential systemic immunologic effects, as evidenced by increased T-cell receptor diversity in some responders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Prospective, Phase 1 Trial of Nivolumab, Ipilimumab, and Radiotherapy in Patients with Advanced Melanoma. Postow, MA., Knox, SJ., Goldman, DA., et al.[2021]

In a phase II study involving 46 patients with high-risk endometrial cancer, the combination of chemotherapy and adjuvant radiation showed excellent local-regional control, with only 2% pelvic and regional recurrence rates at 4 years.

The treatment resulted in an overall survival rate of 85% and a disease-free survival rate of 81% at 4 years, indicating that this combined approach is effective, although distant metastases were more common in advanced-stage patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Final analysis of RTOG 9708: adjuvant postoperative irradiation combined with cisplatin/paclitaxel chemotherapy following surgery for patients with high-risk endometrial cancer. Greven, K., Winter, K., Underhill, K., et al.[2015]

In a review of 98 phase I radiation therapy trials involving 2994 patients, there were significant risks associated with treatment, including 33 treatment-related deaths and 1812 cases of acute grade 3/4 toxicities, resulting in a median toxicity ratio of 0.46.

Trials that included chemotherapy showed a notably higher toxicity ratio (0.60) compared to those without chemotherapy (0.08), indicating that combining chemotherapy with radiation therapy increases the risk of severe side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I trials involving radiation therapy, quantifying the risks. Lawrence, YR., Glass, C., Symon, Z., et al.[2013]

In a Phase II randomized trial involving 90 patients with high-risk prostate cancer, reversing the sequence of radiotherapy (starting with the boost to the prostate) resulted in significantly fewer gastrointestinal (GI) and genitourinary (GU) toxicities that led to chemotherapy dose reductions compared to the standard sequence (5 vs. 15 events).

Despite the reduced toxicity in the experimental sequence, there was no difference in overall survival, cause-specific survival, or biochemical-relapse free survival between the two treatment sequences, indicating that while the new approach may improve tolerability, it does not compromise treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sequence Inversion to Facilitate Concurrent Radiotherapy and Systemic Therapy. A Proof of Principle Study in the Setting of a Phase II Randomized Trial in Prostate Cancer. Wilke, D., Wood, L., Cwajna, S., et al.[2020]

In a study of 133 patients with metastatic cancers receiving immune checkpoint inhibitors and radiation, 34.6% experienced immune-related adverse events (ir-AEs), with higher rates observed in those receiving both CTLA-4 and PD-1 inhibitors (71% vs 29%).

The combination of palliative radiation and immune checkpoint inhibitors was generally well tolerated, with most ir-AEs being mild, suggesting that this treatment approach can be safely integrated in clinical practice for patients needing both therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter Evaluation of the Tolerability of Combined Treatment With PD-1 and CTLA-4 Immune Checkpoint Inhibitors and Palliative Radiation Therapy. Bang, A., Wilhite, TJ., Pike, LRG., et al.[2022]

Combining chemotherapy with radiation therapy has shown significant clinical advancements in cancer treatment, particularly through the use of systemic therapies that can enhance tumor control (radiosensitization) and reduce damage to healthy tissues (radioprotection).

Recent early-phase clinical trials have focused on identifying effective combinations of systemic agents with radiation, suggesting that using surrogate endpoints, like active drug metabolites in tumors, could help streamline the search for optimal treatment schedules, although more robust Phase III trials are still needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New and emerging radiosensitizers and radioprotectors. Spalding, AC., Lawrence, TS.[2007]

Citations

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

Study of RiMO-301 and Radiotherapy With PD-1 Inhibitor ... To determine the efficacy of RiMO-301 with hypofractionated X-ray radiotherapy and a PD-1 inhibitor (pembrolizumab or nivolumab)

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.2527

A phase 1 dose-escalation study of RiMO-301 with ... RiMO-301 with pembrolizumab exhibited 66.7% (4/6) ORR with the 2 remaining patients showing 15-20% tumor size reduction. Preliminary ...

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

RiMO-301 + Radiotherapy for Head and Neck Cancer ... cancer, the 3-year overall survival rate was 71%, indicating that IMRT is an effective treatment option. While IMRT showed promising outcomes, there were ...

4. 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 ... RiMO-301 with pembrolizumab exhibited 66.7% (4/6) ORR with the 2 remaining patients showing 15-20% tumor size reduction. Preliminary ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03444714

Phase I Study of RiMO-301 With Radiation in Advanced ... Participation Criteria · Diagnosis of advanced or metastatic cancer not amenable to curative therapy · Lesion that is amenable to palliative radiotherapy · Lesion ...

6. 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 ...