Chemotherapy Combo for Desmoplastic Small Round Cell Tumor

Age: < 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: Memorial Sloan Kettering Cancer Center

Disqualifiers: Pregnancy, CNS metastases, Hypertension, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

15 Participants Needed

Trial Summary

What is the purpose of this trial?

This study adds irinotecan, temozolomide and bevacizumab to the chemotherapy regimen currently used to treat Desmoplastic small round cell tumor (DSRCT). The investigators are doing this study to find out what effects, good and/or bad, the combination of irinotecan, temozolomide and bevacizumab has on the patient and the DSRCT cancer.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, your hypertension must be well controlled on stable doses of medication for at least two weeks before joining the trial.

What data supports the effectiveness of the drug combination used in the chemotherapy combo for desmoplastic small round cell tumor?

The drug irinotecan, which is part of the chemotherapy combo, has shown significant effectiveness in treating small-cell lung cancer when combined with other drugs like cisplatin, improving survival rates in patients. This suggests that irinotecan may also be beneficial in combination therapies for other cancers, such as desmoplastic small round cell tumor. ^{1 2 3 4 5}

Is the chemotherapy combination of irinotecan and temozolomide safe for humans?

The combination of irinotecan and temozolomide has been studied in humans, showing some dose-limiting side effects like diarrhea, low white blood cell count (neutropenia), and low platelet count (thrombocytopenia). Adjustments in dosing are being explored to improve safety, and ongoing studies aim to find the best doses to minimize these side effects. ^{6 7 8 9 10}

What makes the chemotherapy combo for desmoplastic small round cell tumor unique?

This treatment is unique because it combines Bevacizumab, Irinotecan, and Temozolomide, which are not standard for desmoplastic small round cell tumor, a rare cancer with no established treatment. Bevacizumab targets blood vessel growth in tumors, while Irinotecan and Temozolomide work by interfering with cancer cell DNA, offering a novel approach compared to traditional chemotherapy regimens. ^{1 2 3 5 11}

Research Team

Emily Slotkin, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

This trial is for young patients (1-30 years old) with a rare cancer called Desmoplastic Small Round Cell Tumor who haven't had previous cancer treatments. They need to have good blood counts, controlled blood pressure, and proper liver, heart, and kidney function. Participants must not be pregnant or breastfeeding and should agree to use contraception.

Inclusion Criteria

I have been newly diagnosed with DSRCT and have not received any treatment.

Patients must consent to an indwelling central venous catheter

My kidney function is normal or nearly normal.

Exclusion Criteria

Pregnant or breastfeeding females

I have had chemotherapy or radiotherapy before.

I do not have a bleeding disorder or significant blood clotting issues without taking blood thinners.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemotherapy

Participants receive irinotecan, temozolomide, and bevacizumab in combination with high dose alkylator based therapy

2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Bevacizumab
• Irinotecan
• Temozolomide

Trial Overview The study tests adding irinotecan, temozolomide, and bevacizumab to the existing chemotherapy regimen for DSRCT. The goal is to assess the effects of this combination on both the patient's health and their response to the tumor treatment.

Participant Groups

Group I: Chemotherapy Experimental Treatment 1 Intervention

This is a pilot study to evaluate the acute toxicities and activity of irinotecan, temozolomide, and bevacizumab incorporated into an existing schedule of high dose alkylator based therapy in newly diagnosed patients with DSRCT.

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

Approved in European Union as Avastin for:

• Colorectal cancer
• Breast cancer
• Non-small cell lung cancer
• Renal cell carcinoma
• Ovarian cancer

Approved in United States as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Glioblastoma
• Renal cell carcinoma
• Cervical cancer
• Ovarian cancer

Approved in Japan as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Breast cancer
• Renal cell carcinoma
• Ovarian cancer

Approved in Canada as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Breast cancer
• Renal cell carcinoma
• Ovarian cancer

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Findings from Research

Irinotecan, when combined with cisplatin, significantly improves survival rates in previously untreated patients with extensive-stage small-cell lung cancer, showing a median progression-free survival of 6.9 months compared to 4.8 months with standard treatment (etoposide/cisplatin).

The combination therapy also resulted in a median overall survival of 12.8 months versus 9.4 months for the standard treatment, indicating that irinotecan could be a promising new option for enhancing treatment outcomes in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irinotecan plus cisplatin in small-cell lung cancer. Sandler, A.[2018]

A phase I study found that alternating weekly therapy with irinotecan/cisplatin and etoposide/cisplatin was well-tolerated by patients with small-cell lung cancer, indicating a favorable safety profile for this treatment regimen.

The combination of these drugs demonstrated significant antitumor activity, suggesting a potential clinical advantage for using this approach as a first-line therapy in small-cell lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-dense therapy with a novel irinotecan regimen for small-cell lung cancer. Johnson, FM., Kurie, JM., Peeples, BO., et al.[2018]

Temozolomide is a promising drug for combination therapies due to its ability to cross the blood-brain barrier, good safety profile, and effectiveness against solid tumors like malignant glioma, especially when combined with carmustine or irinotecan.

Studies indicate that administering carmustine before temozolomide results in lower toxicity and a higher maximum tolerated dose, while the combination of temozolomide followed by irinotecan shows greater effectiveness than either drug alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide in combination with other cytotoxic agents. Prados, M.[2019]

This phase I study involving 49 patients aimed to identify the maximum tolerated doses and dose-limiting toxicities of irinotecan and temozolomide, revealing significant gastrointestinal toxicities such as diarrhea and neutropenia at certain dose levels.

Two partial responses were observed in patients with glioblastoma and head and neck cancer, indicating some efficacy of the drug combination, although the recommended doses for phase II trials are still being determined due to ongoing patient accrual.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I. Trial of irinotecan and temozolomide in patients with solid tumors. Jones, SF., Gian, VG., Greco, FA., et al.[2018]

The TMZ-resistant glioma cell line SF188/TR showed a 6-fold resistance to temozolomide and cross-resistance to various other anticancer agents, indicating a significant challenge in treating resistant tumors.

Increased activity of the enzyme alkylguanine alkyltransferase (AGT) was identified as a primary mechanism of resistance to TMZ, while changes in the balance of pro-apoptotic and anti-apoptotic proteins contributed to broader cross-resistance to other drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biochemical changes associated with a multidrug-resistant phenotype of a human glioma cell line with temozolomide-acquired resistance. Ma, J., Murphy, M., O'Dwyer, PJ., et al.[2022]

In a study involving 107 patients with recurrent malignant glioma, the maximum tolerated dose (MTD) of irinotecan (CPT-11) was found to be 325 mg/m² for those taking enzyme-inducing anticonvulsants and 125 mg/m² for those not taking them, indicating significant variability in tolerance based on concurrent medications.

The combination of CPT-11 and temozolomide (TMZ) resulted in a 14% radiographic response rate, with patients showing a median time to disease progression of 54.9 weeks, suggesting that this treatment regimen may be effective for recurrent glioblastoma multiforme.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I trial of irinotecan plus temozolomide in adults with recurrent malignant glioma. Reardon, DA., Quinn, JA., Rich, JN., et al.[2022]

The ECI regimen, which combines irinotecan, cisplatin, and etoposide over three days, demonstrated a high response rate of 77% in advanced-stage small-cell lung cancer patients, indicating its efficacy as a treatment option.

The maximum tolerated dose of irinotecan was established at 140 mg/m², with manageable side effects including febrile neutropenia and grade 3 diarrhea, suggesting that the regimen is well tolerated by patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of etoposide, cisplatin and irinotecan triplet in patients with advanced-stage small-cell lung cancer. Briasoulis, E., Samantas, E., Kalofonos, H., et al.[2018]

References

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

Multiagent chemotherapy including IrIVA regimen and maintenance therapy in the treatment of desmoplastic small round cell tumor. [2022]

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

Irinotecan plus cisplatin in small-cell lung cancer. [2018]

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

Dose-dense therapy with a novel irinotecan regimen for small-cell lung cancer. [2018]

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

Irinotecan therapy for small-cell lung cancer. [2018]

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

Role of topoisomerase I inhibitors in small-cell lung cancer. [2018]

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

Temozolomide in combination with other cytotoxic agents. [2019]

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

Phase I. Trial of irinotecan and temozolomide in patients with solid tumors. [2018]

8. England pubmed.ncbi.nlm.nih.gov

Biochemical changes associated with a multidrug-resistant phenotype of a human glioma cell line with temozolomide-acquired resistance. [2022]

9. England pubmed.ncbi.nlm.nih.gov

What is the place of bevacizumab and irinotecan in the treatment of glioblastoma and other malignant gliomas? [2018]

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

Phase I trial of irinotecan plus temozolomide in adults with recurrent malignant glioma. [2022]

11. Germany pubmed.ncbi.nlm.nih.gov

Phase I study of etoposide, cisplatin and irinotecan triplet in patients with advanced-stage small-cell lung cancer. [2018]