30 Participants Needed

Chemotherapy + Immunotherapy for Rectal Cancer

Md
JC
Overseen ByJohn Cho, MD, PhD
Age: 18+
Sex: Any
Trial Phase: Phase 2
Sponsor: University Health Network, Toronto
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
Approved in 4 JurisdictionsThis treatment is already approved in other countries

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment for cancer patients undergoing surgery. It uses low dose chemotherapy and radiation to weaken the cancer, followed by immunotherapy drugs to help the immune system fight any remaining cancer cells.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot take any other chemotherapy, investigational products, or biologic or hormonal therapy for cancer treatment while participating in this trial.

Is the combination of chemotherapy and immunotherapy safe for rectal cancer treatment?

The combination of PD-1 antibody with chemoradiotherapy for rectal cancer showed good safety, with some patients experiencing mild to moderate side effects. This suggests that similar treatments combining chemotherapy and immunotherapy may be generally safe in humans.12345

How is the drug Cyclophosphamide used in treating rectal cancer different from other treatments?

The combination of chemotherapy and immunotherapy using Cyclophosphamide for rectal cancer is unique because it integrates an immune system-boosting approach with traditional chemotherapy, which is not a standard treatment for rectal cancer. This approach may offer a novel way to enhance the body's ability to fight cancer cells, potentially improving outcomes compared to existing treatments that primarily focus on chemotherapy and radiation.26789

What data supports the effectiveness of the drugs Cyclophosphamide, Cytoxan, Neosar, Endoxan, Tremelimumab, and Durvalumab for rectal cancer?

Research shows that neoadjuvant chemotherapy (treatment given before the main treatment) is effective in reducing local recurrence and distant metastasis in rectal cancer, and combining chemotherapy with radiation therapy is more effective than surgery alone. However, the specific effectiveness of the drugs Cyclophosphamide, Cytoxan, Neosar, Endoxan, Tremelimumab, and Durvalumab for rectal cancer has not been directly established in the provided studies.2691011

Are You a Good Fit for This Trial?

The SMARTEST trial is for adults over 18 with previously untreated mesothelioma, stages I-III. Participants must be fit for surgery, have good organ function, weigh more than 30 kg, and have a life expectancy of at least 12 weeks. They should not have had recent cancer treatments or other clinical trials that could interfere.

Inclusion Criteria

My doctor thinks I can undergo surgery and combined treatment.
I have mesothelioma and have not received any treatment for it.
I weigh more than 30 kilograms.
See 8 more

Exclusion Criteria

I have had radiation therapy to the chest area before.
I have not had major surgery within the last 28 days.
You have participated in a study involving durvalumab or tremelimumab before, no matter which treatment you received.
See 24 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Participants receive sub-ablative radiation, with Arm A also receiving low dose cyclophosphamide

4-6 weeks

Surgery

Participants undergo surgery following radiation treatment

1 week

Adjuvant Immunotherapy

Participants receive consolidation tremelimumab-durvalumab after surgery

Up to 5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

  • Cyclophosphamide
  • Tremelimumab, Durvalumab
Trial Overview This phase II trial tests low dose cyclophosphamide with radiation before surgery (Arm A) against radiation alone (Arm B). After surgery, eligible patients from both arms receive tremelimumab-durvalumab to assess safety and effectiveness.
How Is the Trial Designed?
2Treatment groups
Experimental Treatment
Group I: Radiation+Drug (Arm A)Experimental Treatment3 Interventions
sub-ablative radiation plus low dose cyclophosphamide followed by surgery and adjuvant immunotherapy
Group II: Radiation alone (Arm B)Experimental Treatment2 Interventions
sub-ablative radiation alone followed by surgery and adjuvant immunotherapy

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

πŸ‡ΊπŸ‡Έ
Approved in United States as Cytoxan for:
  • Breast cancer
  • Ovarian cancer
  • Multiple myeloma
  • Leukemia
  • Lymphoma
  • Rheumatoid arthritis
πŸ‡ͺπŸ‡Ί
Approved in European Union as Endoxan for:
  • Breast cancer
  • Ovarian cancer
  • Multiple myeloma
  • Leukemia
  • Lymphoma
  • Rheumatoid arthritis
πŸ‡¨πŸ‡¦
Approved in Canada as Neosar for:
  • Breast cancer
  • Ovarian cancer
  • Multiple myeloma
  • Leukemia
  • Lymphoma
  • Rheumatoid arthritis
πŸ‡―πŸ‡΅
Approved in Japan as Endoxan for:
  • Breast cancer
  • Ovarian cancer
  • Multiple myeloma
  • Leukemia
  • Lymphoma

Find a Clinic Near You

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials
1,555
Recruited
526,000+

Ontario Institute for Cancer Research

Collaborator

Trials
24
Recruited
9,200+

OICR

Collaborator

Trials
4
Recruited
300+

Published Research Related to This Trial

In a study of 3096 patients with locally advanced rectal cancer, elderly patients (over 75 years) had a significantly lower 3-year overall survival rate (77.2%) compared to younger patients (88.9%), indicating age is a critical factor in treatment outcomes.
Despite the age difference, elderly patients in good health can achieve similar cancer-specific survival and disease-free survival rates as younger patients when treated with neoadjuvant chemotherapy combined with chemoradiotherapy and total mesorectal excision.
Oncologic and survival outcomes in elderly patients with locally advanced rectal cancer receiving neoadjuvant chemoradiotherapy and total mesorectal excision.He, F., Chen, M., Xiao, WW., et al.[2021]
Neoadjuvant chemotherapy, specifically regimens like FOLFIRINOX followed by chemoradiotherapy, has shown positive results in patients with locally advanced rectal cancer, establishing new therapeutic standards.
These treatment approaches aim to improve outcomes by reducing the risk of locoregional recurrence, although they have not yet demonstrated a reduction in metastatic recurrence.
[Contribution of neoadjuvant chemotherapy in rectal cancer].Bachet, JB.[2022]
Neoadjuvant chemoradiation, particularly with fluorouracil (5-FU) plus radiation, is now the preferred treatment for stage II/III rectal cancer, showing lower local relapse rates and better safety compared to postoperative treatments.
Capecitabine (Xeloda) plus radiation has been found to be as effective as 5-FU plus radiation, making it a viable alternative, while combinations with oxaliplatin or irinotecan show promise for improved outcomes and warrant further investigation in larger studies.
Neoadjuvant chemoradiation for rectal cancer: is more better?Patel, A., Puthillath, A., Yang, G., et al.[2018]

Citations

Oncologic and survival outcomes in elderly patients with locally advanced rectal cancer receiving neoadjuvant chemoradiotherapy and total mesorectal excision. [2021]
[Contribution of neoadjuvant chemotherapy in rectal cancer]. [2022]
Neoadjuvant chemoradiation for rectal cancer: is more better? [2018]
[Established data and practical recommendations concerning pre- and postoperative chemotherapy of rectal cancer]. [2009]
Even a partial pathological response is associated with lower relapse rates in patients with operable rectal cancer undergoing neoadjuvant chemotherapy. [2021]
Clinical activity and benefit of irinotecan (CPT-11) in patients with metastatic colorectal carcinoma pre-treated with fluorouracil-based chemotherapy. [2018]
Molecular markers of chemotherapeutic response and toxicity in colorectal cancer. [2015]
[Short-term outcome of programmed cell death protein1 (PD-1) antibody combined with total neoadjuvant chemoradiotherapy in the treatment of locally advanced middle-low rectal cancer with high risk factors]. [2022]
[Analysis on safety and preliminary efficacy of dose-modified regimen of 5-fluorouracil plus oxaliplatin and irinotecan (FOLFOXIRI) in advanced colorectal cancer]. [2018]
10.United Statespubmed.ncbi.nlm.nih.gov
Adjuvant therapy for colorectal cancer: present and future perspectives. [2019]
Combined modality therapy of resectable rectal cancer: current approaches. [2005]
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