TILs + Interleukin-2 + Cyclophosphamide for High Grade Serous Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University Health Network, Toronto

Must not be taking: Systemic steroids

Disqualifiers: HIV, Active hepatitis, Cardiac illnesses, 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 explores a new treatment combination for individuals with certain cancers that have resisted other treatments, specifically high-grade serous ovarian, fallopian tube, or primary peritoneal cancer. The study aims to evaluate the effectiveness of a mix of tumor-infiltrating lymphocytes (TILs), interleukin-2 (a type of immunotherapy), and cyclophosphamide (a chemotherapy drug) in combating these cancers. Individuals with these specific cancers who no longer respond to typical platinum-based treatments might be suitable candidates for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial requires that more than 30 days have passed since any prior systemic therapy before the cell infusion, and any side effects from previous treatments must have improved to a mild level. If you are on systemic steroid therapy, you must stop it at least 4 weeks before the TILs infusion, but some topical or inhaled steroids are allowed.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that tumor-infiltrating lymphocytes (TILs) and low-dose interleukin-2 (IL-2) have been used in other cancer treatments, such as metastatic melanoma. These studies have demonstrated promise, with treatments generally well-tolerated by patients. Some patients experienced side effects, which are common in cancer treatments, including flu-like symptoms like fever and chills due to the immune system response.

Since this trial is in its early stages, it focuses on understanding the safety of these treatments for ovarian and related cancers. Early studies have indicated that TILs and IL-2 can be safe and effective, but individual reactions may vary. Participants should discuss any concerns with the medical team conducting the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using re-stimulated tumor-infiltrating lymphocytes (TILs) combined with interleukin-2 for high-grade serous ovarian, fallopian tube, or primary peritoneal cancer because it represents a novel immunotherapy approach. Unlike standard chemotherapy treatments like carboplatin and paclitaxel, this method harnesses the body's own immune system to fight cancer. TILs are extracted from the patient's tumor, re-stimulated in the lab to enhance their cancer-fighting abilities, and then reintroduced into the body, potentially offering a more targeted attack on cancer cells. The addition of interleukin-2 helps to boost the effectiveness of these TILs, possibly leading to better outcomes for patients.

What evidence suggests that this trial's treatments could be effective for high grade serous ovarian, fallopian tube, or primary peritoneal cancer?

Research has shown that using special immune cells called tumor-infiltrating lymphocytes (TILs) with a small amount of a protein called interleukin-2 (IL-2) might be a promising way to treat some cancers. In this trial, participants will receive a combination of re-stimulated TILs and IL-2, with Cyclophosphamide administered beforehand. TILs are immune cells taken from a tumor, grown in a lab, and then reintroduced into the body to help fight cancer. Studies have found that this method has been effective in treating advanced skin cancer, known as metastatic melanoma, which gives hope for its use in treating ovarian cancer. IL-2 enhances these immune cells' ability to attack cancer cells. Although direct evidence for ovarian cancer is limited, the treatment's mechanism suggests it could be effective for hard-to-treat cases. ^{1 2 3 4 5}

Who Is on the Research Team?

Marcus Butler

Principal Investigator

Princess Margaret Cancer Centre

Are You a Good Fit for This Trial?

This trial is for adults over 18 with platinum-resistant high grade serous ovarian, fallopian tube, or primary peritoneal cancer. Candidates must have a life expectancy of more than 3 months and be able to produce suitable TILs. They should not have HIV, active hepatitis B/C, syphilis, HTLV, or brain metastases unless treated. Women must use effective birth control.

Inclusion Criteria

Alkaline phosphatase ≤ 2 x ULN;

Serum creatinine within normal institutional limits OR serum creatinine clearance ≥ 60 mL/min/1.73m2 for patients with creatinine levels above institutional normal;

Serum lipase≤ 1.5 x ULN;

Exclusion Criteria

Subjects cannot be HIV positive.

Subjects cannot have active hepatitis B or hepatitis C, syphilis, or Human T-Cell Lymphotropic Virus (HTLV).

The number of prior lines of chemotherapy is not limited. However, if the subject has had ≥3 lines of prior chemotherapy for platinum refractory or platinum resistant disease, documentation of a response to one of these lines is required. Response can be defined by RECIST 1.1 or CA125 as defined by the modified GCIG criteria (See Section 11).

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-Treatment

Patients receive cyclophosphamide by vein prior to the main treatment

1 week

Treatment

Infusion of autologous tumor-infiltrating lymphocytes (TILs) followed by low-dose interleukin-2 (IL-2) therapy

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

10 years

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• Interleukin-2
• Re-stimulated Tumor-Infiltrating Lymphocytes

Trial Overview The study tests the effectiveness of re-stimulated tumor-infiltrating lymphocytes (TILs) combined with interleukin-2 (IL-2), cyclophosphamide and other agents in patients who haven't responded well to platinum-based chemotherapy. It's an early-phase trial to see how safe and effective this combination therapy is.

How Is the Trial Designed?

Group I: Re-Stimulated Tumor-Infiltrating Lymphocytes and interleukin-2 Experimental Treatment 3 Interventions

Cyclophosphamide will be given prior to Re-Stimulated Tumor-Infiltrating Lymphocytes, and interleukin-2.

Interleukin-2 is already approved in United States, European Union for the following indications:

Approved in United States as Aldesleukin for:

• Metastatic melanoma
• Metastatic renal cell carcinoma

Approved in European Union as PROLEUKIN for:

• Metastatic renal cell carcinoma

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Citations

1. aging.networkofcare.org aging.networkofcare.org/sanmateo/CommunityResources/ClinicalTrials/Detail/NCT01883297?keyword=%22Serous%20Ovarian%20Cancer%22

Re-Stimulated Tumor-Infiltrating Lymphocytes And Low ... This is a phase I clinical study for patients with platinum-resistant (does not respond to platinum-based chemotherapy) high grade serous ovarian, fallopian ...

2. withpower.com withpower.com/trial/phase-1-peritoneal-neoplasms-2015-2db98

TILs + Interleukin-2 + Cyclophosphamide for High Grade ... This is a phase I clinical study for patients with platinum-resistant high grade serous ovarian, fallopian tube, or primary peritoneal cancer, ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6167746/

Adoptive cell transfer using autologous tumor infiltrating ... TIL-based ACT is a highly personalized cancer treatment. T cells are harvested from autologous fresh tumor tissues, and after ex vivo activation and extensive ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4869278/

Adoptive immunotherapy against ovarian cancer - PMC Tumor infiltrating Lymphocytes (TIL). Adoptive transfer of autologous TILs has been successfully tested for the treatment of metastatic melanoma ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0090825824001860

Adoptive T cell therapy for ovarian cancer TILs are typically expanded from tumor fragments in the presence of high-dose IL-2 for 3–5 weeks followed by a rapid expansion of TILs in the presence of ...