DT2216 + Paclitaxel for Ovarian Cancer

Recruiting at 1 trial location

Overseen By Elizabeth Stover, MD, PhD

Age: 18+

Sex: Female

Trial Phase: Phase 1

Sponsor: Elizabeth Stover, MD, PhD

Must not be taking: CYP3A4 inhibitors, CYP2C8 inducers

Disqualifiers: Active infections, CNS metastases, others

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

Compensation: Varies

Number of Visits: 2

Duration: Variable (up to 24 cycles)

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment approach for recurrent ovarian cancer by combining two drugs: DT2216, which breaks down certain cancer proteins, and paclitaxel, a common chemotherapy drug. The main goal is to determine the safest dose of this combination. Women whose ovarian cancer recurs after at least one round of standard chemotherapy may be suitable for this trial. Participants will visit the clinic regularly for monitoring and tests to ensure the treatment's safety and effectiveness. 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 new treatment.

Will I have to stop taking my current medications?

The trial requires that participants stop taking any medications that are strong inhibitors or inducers of the enzymes CYP3A4 or CYP2C8 at least 2 weeks before starting the study. If you are taking such medications, you will need to discontinue them. It's important to discuss all your current medications with the study team to ensure there are no interactions.

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

Earlier studies found that DT2216 was generally well-tolerated when used alone. The most common side effect was a temporary drop in blood platelets, known as thrombocytopenia, which usually did not require stopping the treatment.

The safety of combining DT2216 with paclitaxel remains under investigation. Paclitaxel, a well-known chemotherapy drug, has been used in cancer treatment for a long time. While this trial examines their combined effects, existing knowledge about DT2216 and paclitaxel separately suggests they might be safe to use together. However, as this trial is in the early stages, further research is necessary to fully understand their combined safety in treating ovarian cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of DT2216 and Paclitaxel for treating ovarian cancer because it represents a novel approach compared to standard therapies like surgery, chemotherapy, and targeted therapies. DT2216 operates with a unique mechanism by potentially targeting specific proteins involved in cancer cell survival, which may enhance the effectiveness of Paclitaxel, a well-known chemotherapy drug. This combination aims to maximize the cancer-killing effects while possibly reducing the side effects associated with high doses of chemotherapy. By integrating the action of DT2216, the treatment could offer a more precise attack on cancer cells, potentially leading to better outcomes for patients with fewer adverse effects.

What evidence suggests that this treatment might be an effective treatment for ovarian cancer?

This trial will evaluate the combination of DT2216 with paclitaxel for treating ovarian cancer. Research has shown that using DT2216 with paclitaxel might enhance paclitaxel's effectiveness. While paclitaxel alone has helped some patients, less than half of those with ovarian cancer respond well to it. Recent studies suggest that chemotherapy can increase ovarian cancer cells' sensitivity to DT2216. DT2216 is a drug that breaks down a protein called BCL-XL, which cancer cells need to survive. This combination aims to improve treatment results by making cancer cells easier to target. ^{1 2 3 4 6}

Who Is on the Research Team?

Elizabeth Stover, MD, PhD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

This trial is for individuals with recurrent ovarian cancer that has resisted platinum-based chemotherapy. Participants must have measurable disease and acceptable organ function. Specific details about inclusion or exclusion criteria are not provided, but typically these would cover health status, prior treatments, and other medical conditions.

Inclusion Criteria

Participants must meet specific laboratory criteria including absolute neutrophil count, platelets, total bilirubin, AST/ALT, aPTT, INR, serum albumin, and eGFR

Participants with known HIV infection should meet specific criteria

I can understand and am willing to sign the consent form.

Exclusion Criteria

Participants receiving any other investigational agents within a specified timeframe

Pregnant females are excluded from this study

I have previously received weekly paclitaxel for cancer recurrence.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive DT2216 and Paclitaxel in 28-day cycles with dose escalation and de-escalation

Variable (up to 24 cycles)

Multiple visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days

1 visit (in-person)

Long-term follow-up

Participants are assessed radiologically every 16 weeks after treatment

Variable

What Are the Treatments Tested in This Trial?

Interventions

• DT2216
• Paclitaxel

Trial Overview

The study is testing the highest dose of DT2216 that can be given safely with paclitaxel to patients with recurrent ovarian cancer. DT2216 targets a protein called BCL-XL to induce cancer cell death, while paclitaxel disrupts cell division.

How Is the Trial Designed?

Group I: DT2216 + Paclitaxel Experimental Treatment 2 Interventions

Dose de-escalation and escalation for the DT2216 and Pacllitaxel combination will be guided using a Bayesian Optimal Interval (BOIN) design. Enrolled participants will complete: * Baseline visit * Imaging every 2 cycles * ECG Days 1, 8, and 15 of Cycle 1 and Day 1 of Cycle 2. * Research blood sample Days 1, 2, 4, 8, 15, 16, 18 and 22 of Cycle 1 and Day 1 of every cycle. * Cycle 1 (28 day cycles): * Days 1, 4, 8, 11, 15, 18, 22, and 25: Predetermined dose of DT2216 1x daily * Days 1, 8, 15: Predetermined dose of Paclitaxel 1x daily * Cycle 2 through end of treatment (28 day cycles): * Days 1, 4, 8, 11, 15, 18, 22, 25: Predetermined dose of DT2216 1x daily * Days 1, 8, 15: Predetermined dose of Paclitaxel 1x daily * End of treatment visit with imaging * 30 day follow up visit

Who Is Running the Clinical Trial?

Elizabeth Stover, MD, PhD

Lead Sponsor

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Dialectic Therapeutics, Inc

Industry Sponsor

Trials

1

Recruited

20+

American Society of Clinical Oncology

Collaborator

Trials

40

Recruited

148,000+

Published Research Related to This Trial

Docetaxel combined with carboplatin is a feasible and tolerable first-line treatment option for newly diagnosed epithelial ovarian cancer, showing no significant difference in progression-free or overall survival compared to the traditional paclitaxel and carboplatin combination in a study of 1,077 patients.

While docetaxel was associated with more myelosuppression, it resulted in fewer cases of neuropathy compared to paclitaxel, leading to better quality-of-life outcomes for patients receiving docetaxel.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of docetaxel in the treatment of newly diagnosed advanced ovarian cancer. Vasey, PA.[2018]

The maximum tolerated dose (MTD) for the combination of intravenous docetaxel, intraperitoneal carboplatin, and intraperitoneal paclitaxel was established as docetaxel 75 mg/m², carboplatin AUC 6, and paclitaxel 60 mg/m², but this regimen was not feasible over four treatment cycles due to significant bone marrow toxicity.

Fifteen out of 40 evaluable patients experienced dose-limiting toxicities, including severe neutropenia and infections, indicating that while the treatment shows potential, adjustments such as reducing carboplatin to AUC 5 may be necessary for safer administration in women with advanced ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I study with an expanded cohort to assess feasibility of intravenous docetaxel, intraperitoneal carboplatin and intraperitoneal paclitaxel in patients with previously untreated ovarian, fallopian tube or primary peritoneal carcinoma: a Gynecologic Oncology Group study. Gould, N., Sill, MW., Mannel, RS., et al.[2021]

Cytoreductive surgery followed by platinum-based chemotherapy, particularly with carboplatin, remains the standard treatment for advanced epithelial ovarian cancer, but most patients are not cured, highlighting the need for improved therapies.

Paclitaxel, a novel agent effective in platinum-resistant ovarian cancer, is being tested in combination with platinum compounds in clinical trials for previously untreated patients, aiming to enhance treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of ovarian cancer: current status. Ozols, RF.[2015]

Inhibiting Src family and Abl kinases using siRNAs or dasatinib significantly enhances the sensitivity of ovarian cancer cells to paclitaxel, as demonstrated in both cell cultures and HEY xenograft models.

The mechanism involves the induction of p27(Kip1), which promotes apoptosis by suppressing Bcl-2 and Cdk1 expression, leading to increased effectiveness of paclitaxel treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of p27(Kip1) in dasatinib-enhanced paclitaxel cytotoxicity in human ovarian cancer cells. Le, XF., Mao, W., He, G., et al.[2021]

Paclitaxel has recently become a standard chemotherapy treatment for advanced ovarian cancer, especially when combined with platinum compounds, based on a large randomized trial by the Gynaecologic Oncology Group.

Ongoing clinical trials are investigating the optimal use of paclitaxel, including its dosage, administration schedule, and comparing the effectiveness and side effects of different platinum combinations (carboplatin vs. cisplatin).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

USA update on paclitaxel in ovarian cancer. Ozols, RF.[2019]

Docetaxel shows comparable efficacy to paclitaxel in treating ovarian cancer, with a median progression-free survival of 16 months and a low neurotoxicity rate of 5%, significantly lower than the over 30% seen with paclitaxel.

In a large randomized trial involving 1077 patients, docetaxel combined with carboplatin demonstrated acceptable toxicity and treatment adherence, justifying further analysis of its safety and efficacy compared to the traditional paclitaxel-carboplatin regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The integration of docetaxel into first-line chemotherapy for ovarian cancer. Kaye, SB.[2019]

Paclitaxel and docetaxel, two taxanes used in treating ovarian cancer, have shown clinical activity, with response rates of 20-48% for paclitaxel and 33-35% for docetaxel in previously treated patients, indicating their efficacy even in platinum-resistant tumors.

Premedication with dexamethasone, diphenhydramine, and cimetidine can significantly reduce the risk of severe allergic reactions to taxanes to less than 3%, highlighting a safety measure for patients undergoing treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Options for primary chemotherapy of epithelial ovarian cancer: taxanes. Trimble, EL., Arbuck, SG., McGuire, WP.[2018]

In a study comparing carboplatin combined with either paclitaxel or docetaxel in four ovarian carcinoma cell lines, both combinations showed a synergistic effect, enhancing the growth inhibitory impact on cancer cells.

The combination of carboplatin with paclitaxel produced a broader range of supra-additive effects across various concentrations compared to the carboplatin-docetaxel combination, suggesting that paclitaxel may be more effective in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin-paclitaxel- and carboplatin-docetaxel-induced cytotoxic effect in epithelial ovarian carcinoma in vitro. Engblom, P., Rantanen, V., Kulmala, J., et al.[2019]

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Single-agent DT2216 was well tolerated; the most common toxicity was thrombocytopenia that was typically transient and did not require cessation ...