LY2880070 for Cancer

Recruiting at 16 trial locations

Overseen By Esperas Pharma Inc.

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Esperas Pharma Inc.

Disqualifiers: CNS metastasis, HIV, Hepatitis, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 21-day cycles

229 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new medication called LY2880070 in patients with advanced or spreading solid tumors to see if it can help control their tumor growth.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

What data supports the effectiveness of the drug LY2880070 for cancer?

Gemcitabine, a component of LY2880070, has shown effectiveness in treating various cancers, including non-small cell lung cancer and pancreatic cancer, with a tumor regression rate of about 20%. It is also effective in combination therapies for other cancers like breast and bladder cancer, making it a promising part of LY2880070 for cancer treatment. ^{1 2 3 4 5}

What safety data exists for LY2880070 (Gemcitabine) in humans?

Gemcitabine, also known as LY2880070, has been studied for safety in various trials. Common side effects include mild decreases in blood cells, nausea, and fatigue. Serious side effects are rare but can include interstitial pneumonia, so careful monitoring is recommended. ^{5 6 7 8 9}

What makes the drug LY2880070 unique for cancer treatment?

LY2880070, also known as Gemzar, is a novel form of gemcitabine, which is a pyrimidine antimetabolite that disrupts DNA synthesis in cancer cells. It has shown promising activity against various solid tumors and is being evaluated for its effectiveness in combination with other drugs like erlotinib. This drug is unique because it can be administered orally, unlike traditional gemcitabine, which is typically given intravenously. ^{1 5 6 7 10}

Research Team

Email: [e-mail]

Principal Investigator

Esperas Pharma Inc.

Eligibility Criteria

This trial is for adults with certain advanced or metastatic cancers, including colorectal, breast, ovarian, endometrial cancer and sarcomas. Participants must have measurable tumor lesions and adequate organ function. They should not benefit from standard therapy and agree to use contraception. Exclusions include recent investigational drug use, significant radiation exposure to bone marrow, active secondary cancers within a year (with some exceptions), pregnancy or nursing women, CNS metastasis symptoms, certain viral infections or heart rhythm issues.

Inclusion Criteria

I am fully active or restricted in physically strenuous activity but can do light work.

You are expected to live for at least 12 weeks.

My organs are functioning well.

Exclusion Criteria

My cancer has spread to my brain and is causing symptoms.

Have received treatment with an investigational drug which has not received regulatory approval within 21 days of first study treatment

Your heart's electrical activity takes longer than normal to reset, or you have a condition that causes your heart to take longer to reset.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive multiple oral doses of LY2880070, with Gemcitabine administered intravenously during 21-day cycles

21-day cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Gemcitabine
• LY2880070

Trial Overview The study tests the safety and effectiveness of LY2880070 in combination with Gemcitabine for treating various solid tumors. It's divided into three parts: one focusing on metabolism phenotype related to CYP2D6 enzyme activity; another on specific genetic signatures in high-grade serous ovarian cancer; and the third part assessing broader efficacy across multiple cancer types.

Participant Groups

Group I: Part C: LY2880070 and Gemcitabine (High Grade Serous Ovarian Cancer) Experimental Treatment 2 Interventions

Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously)

Group II: Part B:LY2880070 and Gemcitabine (Ovarian) Experimental Treatment 2 Interventions

Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously)

Group III: Part B: LY2880070 and Gemcitabine (Soft Tissue Sarcoma (STS)) Experimental Treatment 2 Interventions

Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously)

Group IV: Part B: LY2880070 and Gemcitabine (Pancreatic) Experimental Treatment 2 Interventions

Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously)

Group V: Part B: LY2880070 and Gemcitabine (Endometrial) Experimental Treatment 2 Interventions

Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously)

Group VI: Part B: LY2880070 and Gemcitabine (Colorectal) Experimental Treatment 2 Interventions

Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously)

Group VII: Part B: LY2880070 and Gemcitabine (Breast) Experimental Treatment 2 Interventions

Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously)

Group VIII: Part A: LY2880070 with Gemcitabine Experimental Treatment 2 Interventions

Multiple oral doses of LY2880070, and Gemcitabine administered intravenously during 21-day cycles

Group IX: Part A: LY2880070 (Metabolism Phenotype) Experimental Treatment 1 Intervention

Multiple oral doses of LY2880070 administered during 21 day cycles, to participants who are poor metabolizers

Group X: Part A: LY2880070 Experimental Treatment 1 Intervention

Multiple oral doses of LY2880070 during 21-day cycles

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

Approved in European Union as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in United States as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in Canada as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in Japan as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Who Is Running the Clinical Trial?

Esperas Pharma Inc.

Lead Sponsor

Trials

1

Recruited

230+

Findings from Research

LY 188011 (gemcitabine hydrochloride) demonstrated significant antitumor effects in seven out of fifteen human tumor xenograft models in nude mice, including drug-resistant colorectal and lung cancers.

Compared to mitomycin C, LY 188011 was more effective in two lung cancer models and caused fewer side effects, indicating its potential as a promising candidate for clinical cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Antitumor activity of LY 188011, a new deoxycytidine analog, against human cancers xenografted into nude mice]. Fujita, M., Fujita, F., Inaba, H., et al.[2022]

Gemcitabine is an effective treatment for various solid tumors, including non-small-cell lung cancer and pancreatic cancer, with promising results also seen in breast and bladder cancers, based on phase II studies.

The drug has a favorable side-effect profile and may enhance the effectiveness of other DNA-damaging agents, suggesting its potential for use in combination therapies and different treatment schedules.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of gemcitabine in the treatment of other tumours. Carmichael, J.[2022]

Gemcitabine is a highly valuable chemotherapeutic agent for treating both early and advanced non-small cell lung cancer (NSCLC), showing a tumor regression rate of about 20% in patients, regardless of their previous chemotherapy history.

It is particularly effective in combination with platinum-based therapies and can be safely administered alongside radiotherapy, making it a key component in multimodal treatment strategies for NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine (Gemzar) in non-small cell lung cancer. Manegold, C.[2022]

Gemcitabine, a nucleoside analogue, shows promise in treating non-small cell lung cancer (NSCLC) and has been evaluated in economic studies across multiple countries, indicating it may be cost-effective compared to other treatments.

The economic evaluations suggest that gemcitabine can be administered safely in an outpatient setting with a lower side-effect profile, which contributes to its potential cost savings in NSCLC treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of the pharmacoeconomic research on gemcitabine in the treatment of advanced non-small cell lung cancer. Minshall, ME., Liepa, AM.[2022]

LY188011 (Gemcitabine hydrochloride) was found to have a maximum tolerated dose (MTD) of 1,000 mg/m2, with myelosuppression being the main dose-limiting factor observed in a Phase I study involving multiple patients.

The treatment showed anti-cancer effects in some patients with gastric and colon cancers, and the recommended dosing schedule for further studies is 800 mg/m2 weekly for 3 weeks, followed by a week of rest.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[LY188011 phase I study. Research Group of Gemcitabine (LY188011)]. Taguchi, T., Furuse, K., Fukuoka, M., et al.[2022]

The maximum tolerated dose (MTD) of LY2334737, an oral prodrug of gemcitabine, was determined to be 40 mg, with fatigue and elevated liver enzymes identified as the most common dose-limiting toxicities in a study involving 65 patients with advanced cancer.

The study showed promising signs of antitumor activity, with one patient achieving a complete response and 22 patients maintaining stable disease, indicating that further development of LY2334737 is warranted.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of Oral gemcitabine prodrug (LY2334737) alone and in combination with erlotinib in patients with advanced solid tumors. Koolen, SL., Witteveen, PO., Jansen, RS., et al.[2022]

In a Phase I study involving 13 Japanese patients with advanced solid tumors, LY2334737 was found to be tolerable at doses up to 30 mg/day, but the 40 mg/day dose led to significant dose-limiting toxicities, including severe liver issues and thrombocytopenia.

Two patients on the 30 mg/day dose achieved stable disease for 135 and 155 days, indicating some antitumor activity, but the study suggests that alternative dosing schedules may be needed to manage the toxicities observed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of oral gemcitabine prodrug (LY2334737) in Japanese patients with advanced solid tumors. Yamamoto, N., Nokihara, H., Yamada, Y., et al.[2022]

In a late phase II study involving 73 patients with untreated non-small-cell lung cancer (NSCLC), LY188011 (gemcitabine hydrochloride) demonstrated an efficacy response rate of 26%, indicating it can be a viable treatment option for this type of cancer.

The safety profile of LY188011 was generally favorable, with most adverse reactions being mild (grade 1 or 2), although careful monitoring is necessary due to a reported death from interstitial pneumonia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Late phase II study of LY188011 (gemcitabine hydrochloride) in patient with non-small-cell lung cancer. Gemcitabine Late Phase II Cooperative Study Group A)]. Fukuoka, M., Negoro, S., Kudo, S., et al.[2022]

Gemcitabine (GEMZAR) has shown to be an effective treatment for non-small-cell lung cancer (NSCLC) with a response rate of about 21% as a single agent, and it has a mild toxicity profile, making it suitable for combination therapies.

When combined with cisplatin, gemcitabine achieved higher response rates ranging from 38% to 54% and median survival times of 8.4 to 14.3 months, with manageable side effects, indicating its potential as a preferred treatment option in NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination studies with gemcitabine in the treatment of non-small-cell lung cancer. Steward, WP.[2022]

Gemcitabine (2',2'-Difluorodeoxycytidine) shows significant antitumor activity against various human tumors, with a study evaluating 215 tumor specimens revealing a concentration-dependent increase in tumor inhibition, particularly at higher doses (up to 200 micrograms/ml).

The agent demonstrated effectiveness across multiple cancer types, including colorectal, breast, lung, ovarian, kidney, and melanoma, suggesting it should be further tested in Phase II clinical trials targeting these malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activity of 2',2'-difluorodeoxycytidine (Gemcitabine) against human tumor colony forming units. Hanauske, AR., Degen, D., Marshall, MH., et al.[2022]

References

1. Japan pubmed.ncbi.nlm.nih.gov

[Antitumor activity of LY 188011, a new deoxycytidine analog, against human cancers xenografted into nude mice]. [2022]

2. England pubmed.ncbi.nlm.nih.gov

The role of gemcitabine in the treatment of other tumours. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Gemcitabine (Gemzar) in non-small cell lung cancer. [2022]

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

Review of the pharmacoeconomic research on gemcitabine in the treatment of advanced non-small cell lung cancer. [2022]

5. Japan pubmed.ncbi.nlm.nih.gov

[LY188011 phase I study. Research Group of Gemcitabine (LY188011)]. [2022]

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

Phase I study of Oral gemcitabine prodrug (LY2334737) alone and in combination with erlotinib in patients with advanced solid tumors. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

Phase I study of oral gemcitabine prodrug (LY2334737) in Japanese patients with advanced solid tumors. [2022]

8. Japan pubmed.ncbi.nlm.nih.gov

[Late phase II study of LY188011 (gemcitabine hydrochloride) in patient with non-small-cell lung cancer. Gemcitabine Late Phase II Cooperative Study Group A)]. [2022]

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

Combination studies with gemcitabine in the treatment of non-small-cell lung cancer. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Activity of 2',2'-difluorodeoxycytidine (Gemcitabine) against human tumor colony forming units. [2022]