FMC-376 for Solid Tumors

(PROSPER Trial)

Recruiting at 13 trial locations

Overseen By Medical Lead

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Frontier Medicines Corporation

Disqualifiers: Leptomeningeal disease, Carcinomatous meningitis, others

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

Compensation: Varies

Number of Visits: Unknown

403 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this clinical trial is to evaluate FMC-376 in participants with advanced solid tumors with KRAS G12C mutations. This clinical trial will be conducted in 3 parts: Phase 1A (Dose Escalation), Phase 1B (Dose Expansion), and Phase 2 (Cohort Expansion). Multiple dose levels in participants with advanced solid tumors will be evaluated.

Will I have to stop taking my current medications?

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

How does the drug FMC-376 differ from other treatments for solid tumors?

The research provided does not contain specific information about FMC-376, so it's unclear how it differs from other treatments for solid tumors. ^{1 2 3 4 5}

Research Team

Medical Lead

Principal Investigator

Frontier Medicines Corporation

Eligibility Criteria

This trial is for adults with advanced solid tumors that have a specific genetic change called KRAS G12C mutation. They should have tried standard treatments without success or can't tolerate them, and their blood, kidney, and liver functions must be stable. Participants need to be fairly active and well (ECOG status 0 or 1) and agree not to join other drug studies.

Inclusion Criteria

My blood, kidney, and liver tests are within normal ranges.

Agrees not to participate in another interventional study while receiving study drug

My condition worsened or I couldn't tolerate the standard treatment, or it was deemed unsuitable for me.

Exclusion Criteria

My cancer has spread to the lining of my brain or spinal cord.

I do not have any conditions that affect how my body absorbs medication.

Known or suspected hypersensitivity to FMC-376 or any components of the study drug

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive escalating doses of FMC-376 to determine the maximum tolerated dose

21 days

Multiple visits (in-person) during each cycle

Dose Expansion

Participants receive the determined dose of FMC-376 to further evaluate safety and efficacy

21-day cycles

Multiple visits (in-person) during each cycle

Cohort Expansion

Participants are treated with FMC-376 to assess clinical activity in specific cohorts

21-day cycles

Multiple visits (in-person) during each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

Approximately 24 months

Treatment Details

Interventions

• FMC-376

Trial Overview FMC-376 is being tested in people with certain types of cancer like colorectal, lung, and pancreatic cancers. The study has three parts: finding the right dose (Phase 1A), confirming this dose in more patients (Phase 1B), and then testing it in specific groups of patients (Phase 2).

Participant Groups

Group I: FMC-376 Experimental Treatment 1 Intervention

Dose Escalation, Dose Expansion, and Cohort Expansion; Administered for 21-day cycle

Who Is Running the Clinical Trial?

Frontier Medicines Corporation

Lead Sponsor

Trials

1

Recruited

400+

Findings from Research

Fluorouracil (5-FU) combined with levamisole is the standard treatment for node-positive colon cancer, showing significant benefits in disease-free and overall survival without long-term side effects.

While 5-FU can be enhanced with leucovorin to improve response rates and survival, other combinations like semustine have raised safety concerns, limiting their use despite some initial efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current treatment approaches in colorectal cancer. Grem, JL.[2018]

F10, a polymeric fluoropyrimidine, is significantly more potent than 5-fluorouracil (5-FU), showing a 137-314 fold increase in effectiveness depending on the TP53 mutational status in colorectal cancer cell lines.

The study found that TP53 mutations, especially gain-of-function mutations, lead to increased resistance to 5-FU, but F10 remains effective against these resistant cancer cells, suggesting it could improve treatment outcomes for colorectal cancer patients with TP53 mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved potency of F10 relative to 5-fluorouracil in colorectal cancer cells with p53 mutations. Dominijanni, A., Gmeiner, WH.[2022]

Capecitabine, an antimetabolite drug used in cancer treatment, can cause rare but serious side effects like myopericarditis, as demonstrated in a case of a 46-year-old woman who experienced chest pain and elevated cardiac troponin levels after her first dose.

Recognizing and treating capecitabine-induced myopericarditis promptly is crucial to prevent severe cardiac complications, highlighting the need for awareness of this potential toxicity in patients undergoing chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An unusual case of acute myopericarditis after the first dose of capecitabine: Need for new cardioprotective strategies and risk stratification. Meter, M., Gavran, I., Bajo, D., et al.[2021]

Adjuvant systemic therapy with 5-fluorouracil (5-FU) and folic acid is the established standard for treating stage III colorectal cancer, while new studies suggest that capecitabine may replace this standard treatment.

In metastatic colorectal cancer, combining 5-FU/folic acid with agents like CPT-11 or oxaliplatin (FOLFOX) has shown to significantly improve progression-free survival and overall survival, and targeted therapies like bevacizumab and cetuximab are emerging as effective options that enhance treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Adjuvant and palliative anticancer treatment of colon carcinoma in 2004]. Medinger, M., Steinbild, S., Mross, K.[2015]

In a study involving six patients and rabbits with VX2 tumors, 5-fluorouracil (5FU) was found to accumulate in tumors, with a significantly longer half-life in tumors (0.4-2.1 hours) compared to its short half-life in blood (5-15 minutes).

The ability to detect free 5FU in tumors using 19F NMR spectroscopy suggests that the extent of 5FU trapping may correlate with patient response to chemotherapy, highlighting the potential of this method for real-time pharmacokinetic analysis in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor trapping of 5-fluorouracil: in vivo 19F NMR spectroscopic pharmacokinetics in tumor-bearing humans and rabbits. Wolf, W., Presant, CA., Servis, KL., et al.[2019]

References

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

Current treatment approaches in colorectal cancer. [2018]

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

Improved potency of F10 relative to 5-fluorouracil in colorectal cancer cells with p53 mutations. [2022]

3. Germany pubmed.ncbi.nlm.nih.gov

An unusual case of acute myopericarditis after the first dose of capecitabine: Need for new cardioprotective strategies and risk stratification. [2021]

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

[Adjuvant and palliative anticancer treatment of colon carcinoma in 2004]. [2015]

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

Tumor trapping of 5-fluorouracil: in vivo 19F NMR spectroscopic pharmacokinetics in tumor-bearing humans and rabbits. [2019]