110 Participants Needed

Immunotherapy + Radiation for Colorectal and Lung Cancer

Recruiting at 45 trial locations
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial
Breakthrough TherapyThis drug has been fast-tracked for approval by the FDA given its high promise

Trial Summary

What is the purpose of this trial?

This randomized phase II trial studies the side effects of durvalumab and tremelimumab and to see how well they work with or without high or low-dose radiation therapy in treating patients with colorectal or non-small cell lung cancer that has spread to other parts of the body (metastatic). Immunotherapy with durvalumab and tremelimumab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving durvalumab and tremelimumab with radiation therapy may work better in treating patients with colorectal or non-small cell lung cancer.

Will I have to stop taking my current medications?

The trial requires that at least 21 days have passed since your last systemic therapy (like chemotherapy or radiation) before starting the study treatment. If you are currently on any investigational agents or immunosuppressive medications, you will need to stop those before participating.

What data supports the effectiveness of this treatment for colorectal and lung cancer?

The combination of durvalumab and tremelimumab has shown effectiveness in treating certain types of lung cancer and liver cancer, and studies suggest that adding radiotherapy could enhance the immune response against tumors. Additionally, durvalumab has been used successfully after radiotherapy in lung cancer patients, indicating potential benefits for combining these treatments.12345

Is the combination of durvalumab and tremelimumab with or without radiation therapy generally safe for humans?

The combination of durvalumab and tremelimumab has been studied in various cancers and is generally considered to have a tolerable safety profile, though it can lead to significant side effects. In studies, a notable percentage of patients experienced severe adverse events, such as reduced appetite and diarrhea, and when combined with chemotherapy, serious side effects like neutropenia (low white blood cell count) were common. The addition of radiotherapy is being explored for its potential to enhance treatment effects.14678

How is the drug combination of Durvalumab and Tremelimumab with radiation unique for treating colorectal and lung cancer?

This treatment is unique because it combines two immune checkpoint inhibitors, Durvalumab and Tremelimumab, with radiation to potentially enhance the body's immune response against cancer cells, offering a novel approach for patients who may not respond well to standard therapies.245910

Research Team

JD

Jonathan D Schoenfeld

Principal Investigator

Dana-Farber - Harvard Cancer Center LAO

Eligibility Criteria

This trial is for adults with metastatic colorectal or non-small cell lung cancer who've had disease progression after prior therapy. They must have measurable disease, be in good physical condition (ECOG <=1), not pregnant, and willing to use birth control. Exclusions include recent chemotherapy, known allergies to trial drugs, uncontrolled illnesses, HIV-positive status, and certain previous treatments.

Inclusion Criteria

I have been diagnosed with non-small cell lung cancer or colorectal cancer.
My body weight is over 30 kg.
I can have a new biopsy for this study.
See 9 more

Exclusion Criteria

You are currently taking any other experimental drugs.
I haven't had chemotherapy, biologic therapy, or radiotherapy in the last 3 to 6 weeks.
I have not received radiation that would harm my healthy tissues.
See 23 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive tremelimumab and durvalumab with or without high or low-dose radiation therapy

16 weeks
Every 4 weeks

Radiation

Participants receive high or low-dose radiation therapy starting at week 2

10 days for high dose or multiple sessions for low dose

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Treatment Details

Interventions

  • Durvalumab
  • Radiation Therapy
  • Tremelimumab
Trial Overview The study tests the effectiveness of durvalumab and tremelimumab immunotherapies with or without radiation therapy on metastatic cancers. It's a phase II randomized trial where patients are assigned by chance to receive either high/low-dose radiation combined with the drugs or the drugs alone.
Participant Groups
5Treatment groups
Experimental Treatment
Group I: Cohort 2, Arm B (tremelimumab, durvalumab, LD-RT)Experimental Treatment3 Interventions
Patients receive tremelimumab IV and durvalumab IV over 60 minutes every 4 weeks for up to 16 weeks in the absence of disease progression or unacceptable toxicity. Patients then receive durvalumab IV over 60 minutes 4 weeks after last combination dose for up to 9 additional doses. Beginning at week 2, patients receive low dose radiation therapy every 6 hours BID on weeks 2, 6, 10 and 14.
Group II: Cohort 2, Arm A (tremelimumab, durvalumab, HD-RT)Experimental Treatment3 Interventions
Patients receive tremelimumab IV and durvalumab IV over 60 minutes every 4 weeks for up to 16 weeks in the absence of disease progression or unacceptable toxicity. Patients then receive durvalumab IV over 60 minutes 4 weeks after last combination dose for up to 9 additional doses. Beginning at week 2, patients receive high dose radiation therapy QD over 10 days for up to 3 fractions.
Group III: Cohort 1, Arm C (tremelimumab, durvalumab)Experimental Treatment2 Interventions
Patients receive tremelimumab IV and durvalumab IV over 60 minutes every 4 weeks for up to 16 weeks in the absence of disease progression or unacceptable toxicity. Patients then receive durvalumab IV over 60 minutes 4 weeks after last combination dose for up to 9 additional doses.
Group IV: Cohort 1, Arm B (tremelimumab, Durvalumab, LD-RT)Experimental Treatment3 Interventions
Patients receive tremelimumab and durvalumab and as in Arm C. Beginning at week 2, patients receive low dose radiation therapy every 6 hours BID on weeks 2, 6, 10 and 14.
Group V: Cohort 1, Arm A (tremelimumab, durvalumab, HD-RT)Experimental Treatment3 Interventions
Patients receive tremelimumab and durvalumab and as in Arm C. Beginning at week 2, patients receive high dose radiation therapy QD over 10 days for up to 3 fractions.

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

🇪🇺
Approved in European Union as Imfinzi for:
  • Locally advanced, unresectable non-small cell lung cancer (NSCLC)
🇺🇸
Approved in United States as Imfinzi for:
  • Extensive-stage small cell lung cancer (ES-SCLC)
  • Limited-stage small cell lung cancer (LS-SCLC)
  • Locally advanced or metastatic urothelial carcinoma
🇯🇵
Approved in Japan as Imfinzi for:
  • Not specified in provided sources

Find a Clinic Near You

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials
14,080
Recruited
41,180,000+

Findings from Research

Tremelimumab, a CTLA-4 blocking antibody, was approved in the USA in October 2022 for treating unresectable hepatocellular carcinoma (uHCC) in combination with durvalumab, marking a significant advancement in cancer therapy.
In November 2022, tremelimumab was also approved for metastatic non-small cell lung cancer (mNSCLC) when combined with durvalumab and platinum-based chemotherapy, indicating its broad potential in treating various malignant tumors.
Tremelimumab: First Approval.Keam, SJ.[2023]
This phase II study aims to evaluate the safety and efficacy of combining the chemotherapy regimen FOLFOX (5-Fluorouracil, oxaliplatin, and leucovorin) with the immune checkpoint inhibitors durvalumab and tremelimumab in 48 patients with metastatic colorectal cancer (mCRC).
The study hypothesizes that this combination will improve progression-free survival (PFS) rates, expecting a PFS of 70.7% at 6 months, compared to a historical benchmark of 50%.
Phase Ib/II trial evaluating the safety, tolerability and immunological activity of durvalumab (MEDI4736) (anti-PD-L1) plus tremelimumab (anti-CTLA-4) combined with FOLFOX in patients with metastatic colorectal cancer.Fumet, JD., Isambert, N., Hervieu, A., et al.[2023]
Durvalumab is an FDA-approved monoclonal antibody that enhances T-cell responses against cancer by blocking the PD-L1 pathway, specifically for patients with advanced urothelial carcinoma who have progressed after platinum-based chemotherapy.
The drug is currently being tested in phase III trials for various cancers, including lung and head and neck cancers, indicating its potential broad application in oncology beyond urothelial carcinoma.
Durvalumab: First Global Approval.Syed, YY.[2022]

References

Tremelimumab: First Approval. [2023]
Phase Ib/II trial evaluating the safety, tolerability and immunological activity of durvalumab (MEDI4736) (anti-PD-L1) plus tremelimumab (anti-CTLA-4) combined with FOLFOX in patients with metastatic colorectal cancer. [2023]
Durvalumab: First Global Approval. [2022]
Durvalumab plus tremelimumab alone or in combination with low-dose or hypofractionated radiotherapy in metastatic non-small-cell lung cancer refractory to previous PD(L)-1 therapy: an open-label, multicentre, randomised, phase 2 trial. [2023]
DUART: durvalumab after radiotherapy in patients with unresectable, stage III NSCLC who are ineligible for chemotherapy. [2022]
Safety of FOLFIRI + Durvalumab +/- Tremelimumab in Second Line of Patients with Advanced Gastric Cancer: A Safety Run-In from the Randomized Phase II Study DURIGAST PRODIGE 59. [2022]
Durvalumab and tremelimumab combination therapy versus durvalumab or tremelimumab monotherapy for patients with solid tumors: A systematic review and meta-analysis. [2022]
Adverse Events and Tolerability of Combined Durvalumab and Tremelimumab versus Durvalumab Alone in Solid Cancers: A Systematic Review and Meta-Analysis. [2023]
Durvalumab in non-small-cell lung cancer patients: current developments. [2018]
Durvalumab after chemoradiotherapy for locally advanced non-small cell lung cancer prolonged distant metastasis-free survival, progression-free survival and overall survival in clinical practice. [2022]
Unbiased ResultsWe believe in providing patients with all the options.
Your Data Stays Your DataWe only share your information with the clinical trials you're trying to access.
Verified Trials OnlyAll of our trials are run by licensed doctors, researchers, and healthcare companies.
Back to top
Terms of Service·Privacy Policy·Cookies·Security