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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

3 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a phase I clinical study for patients with platinum-resistant high grade serous ovarian, fallopian tube, or primary peritoneal cancer, and the response to a combination of cyclophosphamide, autologous tumor-infiltrating lymphocytes (TILs), autologous dendritic cells (DCs), and OKT3 (anti-CD3 antibody), along with low-dose interleukin-2 (IL-2) 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.

What data supports the effectiveness of this treatment for high grade serous ovarian, fallopian tube, or primary peritoneal cancer?

Research shows that using tumor-infiltrating lymphocytes (TILs) with interleukin-2 (IL-2) and cyclophosphamide has led to significant tumor reduction in patients with ovarian cancer, with some experiencing complete disappearance of the cancer. Additionally, IL-2 alone has shown potential for long-term remission in ovarian cancer cases. ^{1 2 3 4 5}

Is the combination of TILs, Interleukin-2, and Cyclophosphamide safe for humans?

The combination of tumor-infiltrating lymphocytes (TILs), interleukin-2 (IL-2), and cyclophosphamide has been studied in humans, showing some side effects similar to those of IL-2, such as mild lung issues and hyperreactive airways, but no toxic effects were directly linked to TIL infusions. ^{1 2 3 6 7}

How is the treatment of TILs + Interleukin-2 + Cyclophosphamide unique for ovarian cancer?

This treatment is unique because it uses the patient's own immune cells, called tumor-infiltrating lymphocytes (TILs), which are expanded and re-stimulated with interleukin-2 (a protein that boosts immune response) to specifically target and attack cancer cells, offering a personalized approach that differs from standard chemotherapy. ^{1 2 5 8 9}

Research Team

Marcus Butler

Principal Investigator

Princess Margaret Cancer Centre

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

References

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

Use of adoptive transfer of tumor-infiltrating lymphocytes alone or in combination with cisplatin-containing chemotherapy in patients with epithelial ovarian cancer. [2021]

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

Immunotherapy for peritoneal ovarian carcinoma metastasis using ex vivo expanded tumor infiltrating lymphocytes. [2019]

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

Lymphocytes infiltrating human ovarian tumors: synergy between tumor necrosis factor alpha and interleukin 2 in the generation of CD8+ effectors from tumor-infiltrating lymphocytes. [2017]

4. Germany pubmed.ncbi.nlm.nih.gov

A phase II trial of intraperitoneal interleukin-2 in patients with platinum-resistant or platinum-refractory ovarian cancer. [2011]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Prolonged survival after intraperitoneal interleukin-2 immunotherapy for recurrent ovarian cancer. [2020]

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

Immunotherapy of patients with advanced cancer using tumor-infiltrating lymphocytes and recombinant interleukin-2: a pilot study. [2017]

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

Alterations in pulmonary function in cancer patients receiving adoptive immunotherapy with tumor-infiltrating lymphocytes and interleukin-2. [2007]

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

Tumor infiltrating lymphocytes in ovarian cancer. [2022]

9. Germany pubmed.ncbi.nlm.nih.gov

Cellular characteristics of peripheral blood lymphocytes and tumour-infiltrating lymphocytes in patients with gynaecological tumours. [2019]