PT-112 for Thymic Cancer

Overseen By Arun Rajan, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Immunosuppressants, Hormonal agents

Disqualifiers: Active infection, Recent cancer, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

Duration: Up to 8 years

53 Participants Needed

Trial Summary

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, but it mentions that concurrent treatment with a non-permitted drug is not allowed. It's best to discuss your current medications with the study team to determine if any adjustments are needed.

What data supports the effectiveness of the drug PT-112 for thymic cancer?

Research shows that platinum-based chemotherapy, like PT-112, is beneficial for advanced thymic carcinoma, as it has been effective in other studies with similar drugs, leading to tumor shrinkage and improved patient outcomes. ^{1 2 3 4 5}

What safety data exists for PT-112 or similar platinum-based treatments?

Some platinum-based treatments have shown reduced toxicity compared to others, with less impact on kidneys, hearing, and digestion. However, they can still cause side effects like nausea, vomiting, and low white blood cell counts, which can affect the immune system. ^{6 7 8 9 10}

What makes the drug PT-112 unique for treating thymic cancer?

PT-112 is unique because it is a novel platinum-based compound that may offer a different mechanism of action compared to traditional platinum drugs like cisplatin, potentially overcoming resistance seen in some cancer cells. ^{11 12 13 14 15}

What is the purpose of this trial?

This trial is testing a drug called PT-112 to see if it can shrink tumors in adults with thymoma or thymic cancer that has come back or gotten worse after other treatments. PT-112 kills cancer cells and helps the immune system fight the cancer. The study will monitor patients' responses and side effects.

Research Team

Arun Rajan, M.D.

Principal Investigator

National Cancer Institute (NCI)

Eligibility Criteria

Adults aged 18+ with thymoma or thymic carcinoma that has returned or worsened after platinum-based chemotherapy, or those who refused standard treatment. They must have measurable disease, adequate organ and marrow function, and not be pregnant or breastfeeding. Contraception is required for participants of childbearing potential.

Inclusion Criteria

- Ability of participant to understand and the willingness to sign a written informed consent document.

My kidney function, measured by creatinine levels or clearance, is within the required range.

I am not pregnant or breastfeeding, and will not become pregnant during the study.

Exclusion Criteria

I do not have any active infections needing systemic treatment.

I have not had major surgery in the last 2 weeks.

- Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test positive).

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive PT-112 intravenously in 28-day cycles, on Days 1 and 15 of cycle 1, and on day 1 of each subsequent cycle

Up to 8 years

Visits on Days 1 and 15 of cycle 1, and Day 1 of each subsequent cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 years

Follow-up visits 2 weeks and 4 weeks after stopping therapy, then every 3 months

Treatment Details

Interventions

• PT-112

Trial Overview The trial tests PT-112, a drug designed to kill cancer cells and boost the immune system's ability to fight cancer. Participants will receive PT-112 through an infusion on specific days in a 28-day cycle and will continue as long as they tolerate side effects without worsening of their disease.

Participant Groups

Group I: PT-112 Experimental Treatment 1 Intervention

PT-112 will be administered intravenously in 28-day cycles, on Days 1 and 15 at a dose of 360 mg/m2 for cycle 1, and on day 1 at 250mg/m2 for each subsequent cycle, until disease progression, development of intolerable adverse events, or until 8 years after an individual participant has been on study

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a phase II study involving 42 patients with unresectable thymic epithelial tumors, the combination of cisplatin and Genexol-PM showed a high objective response rate of 62.5%, with better outcomes for thymic carcinoma (70%) compared to thymoma (46%).

The treatment was well-tolerated, with no treatment-related deaths reported; however, 26% of patients experienced significant neutropenia, indicating that while effective, monitoring for side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Prospective Phase II Study of Cisplatin and Cremophor EL-Free Paclitaxel (Genexol-PM) in Patients with Unresectable Thymic Epithelial Tumors. Kim, HS., Lee, JY., Lim, SH., et al.[2022]

In a study of 108 patients with advanced thymoma and thymic carcinoma, different front-line chemotherapy regimens (CAP, EP, and TP) showed similar overall survival (OS) rates, indicating that these treatments are comparably effective for long-term outcomes.

The study found that while the objective response rates (ORRs) varied slightly among the regimens (51% for CAP, 50% for EP, and 41% for TP), the median progression-free survival (PFS) and 5-year OS rates were not significantly different, suggesting that the choice of regimen may be flexible without compromising patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical outcomes for patients with thymoma and thymic carcinoma after undergoing different front-line chemotherapy regimens. Ma, WL., Lin, CC., Hsu, FM., et al.[2022]

Two patients with advanced, nonresectable thymomas responded well to a treatment regimen that included high-dose chemotherapy, peripheral blood stem cell transplantation (PBSCT), surgery, and radiotherapy, leading to complete tumor removal.

Both patients maintained disease-free status for significant periods (5 years and 2 years), indicating that this combined treatment approach is effective and well tolerated for advanced thymoma cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multidisciplinary therapy including high-dose chemotherapy followed by peripheral blood stem cell transplantation for invasive thymoma. Iwasaki, Y., Ohsugi, S., Takemura, Y., et al.[2019]

A 74-year-old female with advanced thymic carcinoma showed a partial response to a combination chemotherapy regimen of carboplatin and S-1, marking the first report of its efficacy against this aggressive cancer.

The treatment was well-tolerated, with no severe toxicities or need for dose reductions, suggesting a favorable safety profile for this chemotherapy combination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful chemotherapy with Carboplatin and s-1 for thymic carcinoma: a case report. Igawa, S., Yanagisawa, N., Ishihara, M., et al.[2021]

In three cases of unresectable and locally advanced thymic carcinoma resistant to cisplatin, treatment with carboplatin and paclitaxel as salvage chemotherapy resulted in two patients showing a partial response and one showing a minor response.

The findings suggest that thymic carcinoma is sensitive to platinum-based chemotherapy, and paclitaxel may also be an effective treatment option for this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Salvage chemotherapy with carboplatin and paclitaxel for cisplatin-resistant thymic carcinoma--three cases. Komatsu, Y., Koizumi, T., Tanabe, T., et al.[2015]

CI-973 shows promising efficacy in preclinical models, demonstrating activity comparable or superior to cisplatin and carboplatin, and is effective against cisplatin-resistant cancer cell lines.

In a phase I trial with 28 patients, CI-973 exhibited a favorable safety profile with no renal or auditory toxicity, although mild to moderate nausea and vomiting were common; the maximum tolerated dose was determined to be 290 mg/m2 for patients with good performance status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I clinical evaluation of [SP-4-3(R)]-[1,1-cyclobutanedicarboxylato(2-)](2-methyl-1,4- butanediamine-N,N1) platinum in patients with metastatic solid tumors. Theriault, RL., Cohen, IA., Esparza, L., et al.[2019]

In a Phase II study involving 46 patients with metastatic breast cancer, the combination of carboplatin and etoposide showed a 42% objective response rate in patients who had not received prior chemotherapy, indicating its potential effectiveness as a treatment option.

However, the combination was ineffective in patients who had previously undergone chemotherapy for metastatic cancer, suggesting it may not be suitable for salvage therapy in those cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of carboplatin and etoposide in metastatic breast cancer. Crown, J., Hakes, T., Reichman, B., et al.[2019]

Four different platinum compounds were tested for their effects on immune cells in mice, showing that they significantly suppressed the generation of antibody-producing cells in the spleen after injection.

Despite causing immunosuppression, certain doses of these platinum compounds also led to selective recovery of specific bone marrow precursor cells, indicating a unique pattern of effects with relatively low toxicity to blood cell production.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity of platinum complexes on hemopoietic precursor cells. Wierda, D., Pazdernik, TL.[2022]

The Pt(IV) prodrugs Cx-platin-Cl and Cx-DN604-Cl demonstrated superior cytotoxicity compared to traditional cisplatin and DN604, effectively reversing drug resistance in cancer cells during in vitro studies.

In preclinical models, Cx-platin-Cl not only inhibited tumor growth but also enhanced the immune response by increasing the proliferation of Teff cells and reducing Treg cell recruitment, suggesting its potential as an immunotherapeutic agent against chemo-immune resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging JWA-targeted Pt(IV) prodrugs conjugated with CX-4945 to overcome chemo-immune-resistance. Chen, F., Pei, S., Wang, X., et al.[2021]

Carboplatin, when administered intravenously to Wistar rats, caused significant suppression of blood cell production in the bone marrow, leading to conditions like anemia, leukopenia, and thrombocytopenia within the first month of treatment.

In addition to immediate effects, carboplatin also induced chromosomal damage in mice and showed greater myelotoxicity compared to cisplatin, with long-term impacts on blood cell production and immune organ health observed up to 6 months post-treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early and delayed effects of carboplatin on the blood system. Karpova, GV., Fomina, TI., Voronova, OL., et al.[2019]

Tetraplatin was found to be therapeutically effective in treating both cisplatin-resistant (L1210/DDPt) and sensitive (L1210/0) leukemia in mice, suggesting its potential as an alternative treatment for resistant cases.

The study showed that the sensitivity of leukemia cells to platinum compounds varies with concentration, with L1210/0 cells being more sensitive to both cisplatin and tetraplatin compared to L1210/DDPt cells, indicating that the effectiveness of these drugs can depend on the specific cell line and dosage used.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of trans-tetrachloro-1,2-diaminocyclohexane platinum (IV) in murine leukemia L1210 resistant and sensitive to cis-diamminedichloroplatinum (II). Wilkoff, LJ., Dulmadge, EA., Trader, MW., et al.[2019]

Preliminary clinical trials of eight platinum analogs have identified effective dosages and limiting toxicities for racemic malonato-1,2-diaminocyclohexaneplatinum(II) (PHM) and its isomer neo-PHM, suggesting potential for further development.

While three of the tested compounds were abandoned due to toxicity or ineffectiveness, ongoing trials for PHM and neo-PHM in combination with standard treatments indicate they may offer improved safety and efficacy compared to the widely used cis-dichlorodiammineplatinum(II).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Platinum analogs of clinical interest. Hill, JM., Loeb, E., Pardue, A., et al.[2013]

New platinum(II) complexes with N-cyclohexyl-1,3-propanediamine as a carrier have been synthesized and shown to have strong anticancer activity, particularly against human lung cancer and leukemia cell lines, outperforming carboplatin.

The structural analysis confirmed that these complexes have a square planar geometry, which is important for their function, and the compounds demonstrated effective binding properties that enhance their potential as alternative anticancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preparation, characterization and in vitro anticancer activity of platinum(II) complexes with N-Cyclohexyl-1,3-propanediamine as the carrier. Liu, W., Qing, C., Chen, X., et al.[2019]

The newly synthesized platinum(II) complexes, MMF3 and MPF4, showed anti-tumor activity against human ovarian carcinoma cell lines but were less effective than the well-known drug cisplatin.

Both complexes demonstrated cross-resistance with cisplatin in resistant cell lines and were inactive against HIV, indicating limited therapeutic potential compared to existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Perfluorophtalate Complexes of Platinum(II) With Chemotherapeutic Potential. de Oliveira, MB., Miller, J., Banks, RE., et al.[2021]

The new bis(platinum) complex (1,1/t,t) shows promising anti-cancer activity against cis-DDP-resistant cells, with a lower resistance factor compared to a previously studied bidentate complex (2,2/c,c), indicating its potential effectiveness in overcoming drug resistance.

This complex also demonstrates more efficient DNA interstrand cross-linking and unique binding sites on DNA, which could enhance its therapeutic action in treating cancers like ovarian carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of chemical reactivity, cytotoxicity, interstrand cross-linking and DNA sequence specificity of bis(platinum) complexes containing monodentate or bidentate coordination spheres with their monomeric analogues. Farrell, N., Qu, Y., Feng, L., et al.[2019]

References

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

A Prospective Phase II Study of Cisplatin and Cremophor EL-Free Paclitaxel (Genexol-PM) in Patients with Unresectable Thymic Epithelial Tumors. [2022]

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

Clinical outcomes for patients with thymoma and thymic carcinoma after undergoing different front-line chemotherapy regimens. [2022]

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

Multidisciplinary therapy including high-dose chemotherapy followed by peripheral blood stem cell transplantation for invasive thymoma. [2019]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Successful chemotherapy with Carboplatin and s-1 for thymic carcinoma: a case report. [2021]

5. Greece pubmed.ncbi.nlm.nih.gov

Salvage chemotherapy with carboplatin and paclitaxel for cisplatin-resistant thymic carcinoma--three cases. [2015]

6. Germany pubmed.ncbi.nlm.nih.gov

Phase I clinical evaluation of [SP-4-3(R)]-[1,1-cyclobutanedicarboxylato(2-)](2-methyl-1,4- butanediamine-N,N1) platinum in patients with metastatic solid tumors. [2019]

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

Phase II trial of carboplatin and etoposide in metastatic breast cancer. [2019]

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

Toxicity of platinum complexes on hemopoietic precursor cells. [2022]

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

Emerging JWA-targeted Pt(IV) prodrugs conjugated with CX-4945 to overcome chemo-immune-resistance. [2021]

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

Early and delayed effects of carboplatin on the blood system. [2019]

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

Evaluation of trans-tetrachloro-1,2-diaminocyclohexane platinum (IV) in murine leukemia L1210 resistant and sensitive to cis-diamminedichloroplatinum (II). [2019]

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

Platinum analogs of clinical interest. [2013]

13. Japan pubmed.ncbi.nlm.nih.gov

Preparation, characterization and in vitro anticancer activity of platinum(II) complexes with N-Cyclohexyl-1,3-propanediamine as the carrier. [2019]

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

New Perfluorophtalate Complexes of Platinum(II) With Chemotherapeutic Potential. [2021]

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

Comparison of chemical reactivity, cytotoxicity, interstrand cross-linking and DNA sequence specificity of bis(platinum) complexes containing monodentate or bidentate coordination spheres with their monomeric analogues. [2019]