Molecular Tumor Board Recommendations for Cancer

(CATRINA Trial)

Overseen By Jacob R Dubien

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Dartmouth-Hitchcock Medical Center

Disqualifiers: Untreated genetic alteration, Pregnancy

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 36 months

174 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a single-arm Phase II study to measure the impact of Molecular Tumor Board treatment recommendations on treatment decision-making in clinical practice at the Dartmouth Cancer Center. Following tumor genetic profiling, subjects will be screened for eligibility. Eligible subjects' cases will be evaluated by the Dartmouth Cancer Center Molecular Tumor Board, and treatment recommendations will be entered into the medical record as per standard procedure. The primary endpoint is a survey response from the treating physician indicating how Molecular Tumor Board evaluation impacted treatment decisions. Secondary endpoints include: 1) Molecular Tumor Board treatment recommendation; 2) disease progression on line of therapy started after MTB recommendations were made. Surveys will be administered approximately 3 and 12 months after Molecular Tumor Board recommendations are made.

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

The trial protocol does not specify whether you need to stop taking your current medications. It is best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug Keytruda (pembrolizumab) for cancer treatment?

Keytruda (pembrolizumab) has been shown to be effective in treating various cancers, including non-small cell lung cancer and melanoma, by improving survival rates and reducing tumor size. It works by blocking a pathway that cancer cells use to hide from the immune system, allowing the body to better fight the cancer. ^{1 2 3 4 5}

Is pembrolizumab (Keytruda) generally safe for humans?

Pembrolizumab (also known as Keytruda, lambrolizumab, MK-3475) has been approved by the FDA for various cancers, showing it is generally safe for human use. Common side effects include fatigue, cough, nausea, and rash, while some serious immune-related side effects like lung inflammation and thyroid issues have been reported. ^{1 2 3 5 6}

How is the drug Keytruda different from other cancer treatments?

Keytruda (pembrolizumab) is unique because it is a PD-1 inhibitor, which means it helps the immune system recognize and attack cancer cells by blocking a pathway that tumors use to hide from immune cells. This mechanism is different from traditional chemotherapy, which directly targets and kills rapidly dividing cells. ^{1 2 4 5 7}

Eligibility Criteria

This trial is for adults over 18 with cancer, who are fairly active (ECOG Performance Status of 0 to 2), have tumors that can be measured or evaluated, and have given verbal consent. Their tumor must have been genetically profiled with at least 100 genes and contain certain genetic alterations that could respond to treatment.

Inclusion Criteria

You need to agree by speaking that you want to be in the study before your case is reviewed.

I can join this study again if my cancer was retested after getting worse despite treatment.

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

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Molecular Tumor Board Evaluation

Eligible subjects' cases are evaluated by the Molecular Tumor Board, and treatment recommendations are entered into the medical record

1 month

Treatment

Participants receive treatment based on Molecular Tumor Board recommendations, including tumor-targeted therapy or immunotherapy

Up to 36 months

Follow-up

Participants are monitored for disease progression and treatment impact, with surveys administered at 3 and 12 months

36 months

Treatment Details

Interventions

• Treatment recommendations made by Molecular Tumor Board

Trial Overview The study tests how recommendations from the Dartmouth Cancer Center's Molecular Tumor Board affect doctors' treatment decisions. After genetic profiling of tumors, these personalized recommendations are made and their impact is assessed through physician surveys.

Participant Groups

Group I: Subjects evaluated by Molecular Tumor Board Experimental Treatment 1 Intervention

Subjects whose cases are evaluated by Molecular Tumor Board

Treatment recommendations made by Molecular Tumor Board is already approved in European Union, United States, Japan for the following indications:

Approved in European Union as Keytruda for:

• Melanoma
• Non Small Cell Lung Cancer
• Head and Neck Cancer
• Hodgkin's Lymphoma
• Stomach Cancer
• Cervical Cancer
• Breast Cancer

Approved in United States as Keytruda for:

• Melanoma
• Non Small Cell Lung Cancer
• Head and Neck Cancer
• Hodgkin's Lymphoma
• Stomach Cancer
• Cervical Cancer
• Breast Cancer
• Urothelial Carcinoma
• Endometrial Cancer

Approved in Japan as Keytruda for:

• Melanoma
• Non Small Cell Lung Cancer
• Head and Neck Cancer
• Hodgkin's Lymphoma
• Stomach Cancer
• Cervical Cancer
• Breast Cancer

Who Is Running the Clinical Trial?

Dartmouth-Hitchcock Medical Center

Lead Sponsor

Trials

548

Recruited

2,545,000+

Findings from Research

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

Pembrolizumab (Keytruda) is approved for treating advanced endometrial carcinoma that is microsatellite instability-high or mismatch repair deficient, specifically for patients whose disease has progressed after previous treatments.

This approval is significant for patients who are not candidates for curative surgery or radiation, providing a new therapeutic option for a challenging stage of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Approved Use for Keytruda. Aschenbrenner, DS.[2022]

Pembrolizumab (Keytruda) was approved by the FDA for treating metastatic non-small cell lung cancer (mNSCLC) in patients with tumors expressing PD-L1, showing significant improvements in overall survival (OS) and progression-free survival (PFS) in two major clinical trials with thousands of participants.

In the KEYNOTE-024 trial, pembrolizumab demonstrated a 40% reduction in the risk of death compared to chemotherapy, while in the KEYNOTE-010 trial, it also showed a significant survival advantage over chemotherapy in patients who had previously progressed on treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. Pai-Scherf, L., Blumenthal, GM., Li, H., et al.[2022]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating unresectable or metastatic melanoma based on two clinical trials involving 1,374 patients, showing significant improvements in overall survival compared to ipilimumab, with hazard ratios indicating a reduced risk of death.

Patients receiving pembrolizumab also experienced significant improvements in progression-free survival, although some immune-mediated adverse reactions like hypothyroidism and pneumonitis were noted, highlighting the importance of monitoring for side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. Barone, A., Hazarika, M., Theoret, MR., et al.[2022]

Pembrolizumab (Keytruda) has been approved by the FDA for treating high-risk, non-muscle invasive bladder cancer (NMIBC) in patients who are unresponsive to BCG therapy and are either ineligible for or have opted not to undergo cystectomy.

This approval specifically targets patients with carcinoma in situ (CIS) with or without papillary tumors, highlighting its role as a treatment option for those with limited surgical options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approves Pembrolizumab for BCG-Unresponsive NMIBC. Wright, KM.[2021]

References

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

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]

2. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

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

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]

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

New Approved Use for Keytruda. [2022]

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

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. [2022]

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

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. [2022]

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

FDA Approves Pembrolizumab for BCG-Unresponsive NMIBC. [2021]