CPI-0209 + Carboplatin for Ovarian Cancer

Overseen By Kelsey Mitch, RN

Age: 18+

Sex: Female

Trial Phase: Phase 1

Sponsor: Lan Coffman

Must not be taking: Warfarin, Herbal supplements

Disqualifiers: Platinum-resistant disease, HIV, Active infection, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for individuals with recurring ovarian cancer that responds well to platinum-based chemotherapy. The combination includes CPI-0209, an experimental drug, and Carboplatin, a standard chemotherapy drug. The trial aims to determine if this combination can improve outcomes for patients whose cancer returned at least six months after their last round of platinum-based treatment. Individuals who have undergone at least one previous round of platinum-based chemotherapy and whose cancer has returned may 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 new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot take warfarin or certain herbal supplements. Foods like grapefruit that affect drug metabolism must be avoided starting 7 days before the trial.

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

Research is examining the safety of using CPI-0209 with carboplatin for ovarian cancer patients. Early trials have tested CPI-0209 to assess its tolerability. Some studies suggest it can be safe when combined with carboplatin, a common chemotherapy drug.

However, because CPI-0209 remains in early testing, limited information exists about its long-term safety. In these trials, researchers aim to understand the body's reaction to the drug and any potential side effects. So far, these studies indicate that the treatment is generally well-tolerated.

Carboplatin is already used in treatments and is generally considered safe for many patients, though it can cause side effects like nausea or low blood cell counts. The goal of combining CPI-0209 with carboplatin is to improve treatment outcomes, but safety details are still under investigation. Always consult a doctor for personalized advice. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about CPI-0209 combined with carboplatin for ovarian cancer because it introduces a novel approach to treatment. Unlike standard chemotherapy options, which typically rely on disrupting cell division, CPI-0209 is a new compound that targets the epigenetic regulation of cancer cells, potentially silencing genes that promote tumor growth. This mechanism offers a fresh avenue for tackling cancer cells that might be resistant to existing treatments. Additionally, the combination of CPI-0209 with carboplatin could enhance the effectiveness of the chemotherapy by making cancer cells more susceptible to treatment, offering hope for improved outcomes.

What evidence suggests that this trial's treatments could be effective for ovarian cancer?

Research shows that CPI-0209, one of the treatments studied in this trial, may enhance ovarian cancer's response to platinum-based chemotherapy, such as Carboplatin. Studies have found that CPI-0209, also known as tulmimetostat, has been effective in ovarian cancer models with specific genetic changes. It has improved the efficacy of treatments like cisplatin, which is similar to Carboplatin. This trial will test CPI-0209 in combination with Carboplatin, with participants receiving either 100 mg or 150 mg of CPI-0209. These findings offer hope for better outcomes for patients with this type of cancer. ^{1 2 5 6 7}

Who Is on the Research Team?

Lan G Coffman, MD

Principal Investigator

UPMC Magee Women's Hospital

Are You a Good Fit for This Trial?

This trial is for women with ovarian cancer that has returned more than 6 months after platinum-based chemotherapy. They must be able to take oral medication, have a life expectancy of at least 3 months, and agree to use effective contraception. Exclusions include certain medical conditions, recent treatments or surgeries, and those not recovered from previous therapy side effects.

Inclusion Criteria

I had brain metastasis treated over 8 weeks ago, am off steroids for 4 weeks, and my condition is stable or improved.

I agree to use effective birth control or abstain from sex for 6 months after the study ends.

I've had platinum-based therapy and possibly bevacizumab or PARPi. I may have a BRCA mutation.

Exclusion Criteria

I haven't had major surgery in the last 2 weeks or still have major side effects from it.

I had radiotherapy recently and still experience side effects.

I have a history of HIV infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive CPI-0209 in combination with Carboplatin chemotherapy

24 months

Maintenance

Participants continue with CPI-0209 maintenance therapy to prolong disease-free interval

Up to 5.5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

5.5 years

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• CPI-0209

Trial Overview The study tests CPI-0209 combined with Carboplatin followed by maintenance CPI-0209 in patients with recurrent ovarian cancer who responded well previously to platinum-based treatment. The goal is to see if this combination helps control the cancer better than current treatments.

How Is the Trial Designed?

Group I: CPI-0209 (150 mg) + carboplatin Experimental Treatment 2 Interventions

CPI-0209: 100 mg (oral dosing) carboplatin administered intravenously as per institutional standards

Group II: CPI-0209 (100 mg) + carboplatin Experimental Treatment 2 Interventions

CPI-0209: 100 mg (oral dosing) carboplatin administered intravenously as per institutional standards

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

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

Lan Coffman

Lead Sponsor

Trials

1

Recruited

30+

MorphoSys AG

Industry Sponsor

Trials

27

Recruited

6,600+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Novartis Pharmaceuticals

Industry Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Published Research Related to This Trial

In this ongoing phase I study involving 24 previously untreated patients with advanced non-small cell lung cancer, the maximum tolerated dose of the combination of carboplatin and paclitaxel was established at 185 mg/m2 and 350 mg/m2, respectively.

The combination treatment demonstrated an excellent safety profile, with minimal instances of neutropenia and no cases of thrombocytopenia or infection, indicating it may be a well-tolerated option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preliminary results of a dose-finding study of paclitaxel and carboplatin in patients with advanced non-small cell lung cancer. Scagliotti, GV., Crinó, L., Pozzi, E., et al.[2015]

In a phase II study, carboplatin showed a clinical response rate of 28% in women with ovarian carcinoma who had persistent or recurrent tumors after cisplatin treatment, particularly benefiting those with smaller tumors and longer intervals since their last treatment.

A phase III trial found that while carboplatin and cyclophosphamide/cisplatin had comparable efficacy, the carboplatin regimen was easier to administer and resulted in less toxicity, making it a preferable option despite overall disappointing long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin in the treatment of carcinoma of the ovary: the National Cancer Institute of Canada experience. Ovarian Cancer Subcommittee. Swenerton, KD., Pater, JL.[2018]

In a dose-escalation study involving 25 patients with epithelial ovarian cancer, the combination of intraperitoneal cisplatin and carboplatin showed a high overall response rate of 80%, indicating strong efficacy of this treatment regimen.

The maximum tolerated dose of carboplatin was determined to be AUC 7 mg/ml x min, suggesting that this dosage is safe for further investigation in a phase II study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I study of cisplatin i.p. and carboplatin i.v. with G-CSF in patients with ovarian cancer. Adachi, S., Ito, K., Itani, Y., et al.[2019]

In a study of 27 ovarian cancer patients treated with Carboplatin, only 19% (5 patients) showed an objective response to the treatment, indicating limited efficacy.

Drug resistance was noted during the first course of therapy, suggesting that Carboplatin may not be effective for all patients and highlighting the need for alternative treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Role of carboplatin in treating patients with advanced ovarian cancer]. Pawlicki, M., Koralewski, P.[2017]

Carboplatin, a new analogue of cisplatin, has a similar effectiveness in treating cancers, particularly in platinum-sensitive tumors, emphasizing the importance of dosage for maximizing its efficacy.

In ovarian cancer patients, the recommended carboplatin dose ranges from 300 to 400 mg/m2, tailored based on the patient's renal function and chemotherapy history, highlighting the need for personalized treatment plans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimal dosing with carboplatin. Ozols, RF.[2018]

The combination of carboplatin and 3-hour infusional paclitaxel was well-tolerated in a study of 92 women with advanced gynecologic cancers, showing a manageable toxicity profile with neutropenia being the most significant side effect.

In patients with ovarian cancer or primary peritoneal carcinoma, 74% experienced a significant decline in tumor marker levels after treatment, indicating strong antineoplastic activity of this chemotherapy regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin plus paclitaxel in the treatment of gynecologic malignancies: the Cleveland Clinic experience. Markman, M., Kennedy, A., Webster, K., et al.[2015]

In a phase II study involving 43 patients with advanced ovarian cancer who had previously failed platinum therapy, carboplatin demonstrated antitumor activity, achieving four complete and eight partial responses.

The treatment was associated with significant hematologic toxicity, particularly severe thrombocytopenia in one-third of patients, suggesting that a lower starting dose of carboplatin is advisable to minimize side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of carboplatin in patients with ovarian carcinoma: a National Cancer Institute of Canada Clinical Trials Group Study. Eisenhauer, EA., Swenerton, KD., Sturgeon, JF., et al.[2013]

In a phase I/II trial involving 27 patients with advanced gynecologic cancers, intraperitoneal (IP) carboplatin showed promising efficacy, with eight patients remaining free of disease progression for over 2 years despite extensive prior treatments.

The study identified myelosuppression, particularly thrombocytopenia, as the main dose-limiting toxicity, leading to a recommended starting dose of 400 mg/m2 for most patients, while those with compromised renal function should start at 200 mg/m2.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraperitoneal carboplatin: rationale and experience. Speyer, JL., Sorich, J.[2018]

In a phase II study involving 50 evaluable ovarian cancer patients, carboplatin demonstrated an overall response rate of 38%, with a notably higher response of 54.2% in patients who had not received prior chemotherapy.

While carboplatin was associated with common hematologic toxicities like leukopenia and thrombocytopenia, these were generally well tolerated, indicating that carboplatin is a useful treatment option for ovarian cancer with manageable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Phase II study of carboplatin in ovarian cancer]. Kato, T., Nishimura, H., Yamabe, T., et al.[2013]

In a phase II study involving 66 patients with recurrent platinum-sensitive ovarian cancer, the combination of pemetrexed and carboplatin achieved an overall response rate of 32.8%, indicating its potential effectiveness in treating this condition.

The treatment was associated with manageable toxicity, with the most common severe side effects being neutropenia and thrombocytopenia, and only one drug-related death reported, suggesting a relatively low incidence of serious adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II trial of pemetrexed in combination with carboplatin in patients with recurrent ovarian or primary peritoneal cancer. Sehouli, J., Alvarez, AM., Manouchehrpour, S., et al.[2015]

Carboplatin, as a first-line treatment for advanced ovarian cancer, shows clinical complete response rates that are comparable to or exceed those of cisplatin, based on phase III trials.

Carboplatin not only achieves similar efficacy to cisplatin but also has significantly lower toxicity, resulting in reduced side effects like nausea, hearing loss, nerve damage, and kidney issues, making it the preferred choice for treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin in the first-line chemotherapy of ovarian cancer. Alberts, DS., Canetta, R., Mason-Liddil, N.[2018]

In a study of 33 patients with ovarian cancer who had progressed after taxane therapy, 21% showed partial responses to carboplatin reinduction, particularly those with a platinum-free interval of at least 12 months.

Carboplatin was well tolerated with no neurotoxicity observed, suggesting it may be a safe option for patients who initially responded to taxanes and had a significant break from platinum-based treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin reinduction after taxane in patients with platinum-refractory epithelial ovarian cancer. Kavanagh, J., Tresukosol, D., Edwards, C., et al.[2017]

In a study involving 44 patients with recurrent childhood brain tumors, carboplatin was found to have a disease-specific response rate of 43% in medulloblastoma, indicating its potential effectiveness in treating this type of cancer.

Carboplatin demonstrated a favorable safety profile with mild side effects, such as low emetic effects and no significant auditory or renal toxicity, making it a promising candidate for further studies in combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin and recurrent childhood brain tumors. Allen, JC., Walker, R., Luks, E., et al.[2017]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05942300

CPI-0209 Plus Carboplatin in Patients With Platinum ... This study aims to investigate whether CPI-0209 will enhance ovarian cancer sensitivity to platinum-based chemotherapy and prolong the disease free interval ...

2. veri.larvol.com veri.larvol.com/news/cpi-0209/drug

News - tulmimetostat (DZR123) Tulmimetostat administration achieved efficacy in multiple ARID1A mutant bladder, ovarian, and endometrial tumor models and improved cisplatin response.

3. novartis.com novartis.com/clinicaltrials/study/nct04104776

A Study of Tulmimetostat DZR123 (CPI-0209) in Patients ... The purpose of this open-label, first-in-human (FIH) trial is to evaluate the safety, tolerability, and preliminary clinical activity of Tulmimetostat as a ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12345763/

Epigenetic Therapies in Endocrine-Related Cancers A Randomized Phase II Trial of Epigenetic Priming with Guadecitabine and Carboplatin in Platinum-resistant, Recurrent Ovarian Cancer. Clin ...

5. facingourrisk.org facingourrisk.org/research-clinical-trials/results?amp%3Bintervention_type=risk%20reduction&amp%3Bkeyword=&amp%3Bstudy_type=prevention_detection_risk&cancer_type=ovarian

Research & Clinical Trials Search Results: Ovarian Cancer CPI-0209 Plus Carboplatin in Patients With Platinum Sensitive Recurrent Ovarian Cancer ... A Clinical Trial to Evaluate the Safety and Efficacy of COM701 ...

6. sigma.larvol.com sigma.larvol.com/product.php?e1=748185&tab=newstrac

tulmimetostat (DZR123) News New P1 trial, Platinum sensitive: CPI-0209 Plus Carboplatin in Patients With Platinum Sensitive Recurrent Ovarian Cancer (clinicaltrials.gov) - Jul 12, 2023

7. cancer.gov cancer.gov/research/participate/clinical-trials/intervention/tulmimetostat?pn=1

Clinical Trials Using Tulmimetostat - NCI CPI-0209 in Combination with Carboplatin for the Treatment of Patients with Platinum Sensitive Recurrent Ovarian, Fallopian Tube or Primary Peritoneal Cancer.