Tadalafil + Chemotherapy for Stomach Cancer

Overseen By Rachel E Jarrett

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Arizona

Must not be taking: Nitrates, α-blockers

Disqualifiers: Metastatic disease, Cardiovascular disorders, Autoimmune disease, others

Stay on Your Current Meds You can continue your current medications while participating

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if Tadalafil (also known as Cialis), used alone or with chemotherapy, can control stomach cancer by reducing cells that suppress the immune system. It will assess the safety and practicality of this treatment combination and its impact on the cancer environment. The trial seeks participants with specific types of stomach cancer that can be surgically removed, who have not received previous treatments for their cancer, and do not have any known spread of the disease. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it does exclude those using certain medications like nitrates, α-blockers, and some other interacting drugs. It's best to discuss your current medications with the trial team to see if they might affect your eligibility.

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

Research shows that Tadalafil, a drug commonly used for erectile dysfunction, is usually well-tolerated. Studies have examined its use with FLOT chemotherapy (a combination of 5-Fluorouracil, Oxaliplatin, and Docetaxel) for treating stomach cancer. These studies suggest that this combination might reduce certain cells that aid tumor growth. Although direct information on side effects is limited, earlier studies found no major increase in tumor growth or spread with Tadalafil use.

This trial is in an early stage, indicating some safety has been demonstrated in humans, but more data is needed to confirm its safety when combined with chemotherapy. Participants will first receive Tadalafil alone, followed by chemotherapy. Researchers will closely monitor any potential side effects to ensure safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for stomach cancer involve chemotherapy, which attacks rapidly dividing cancer cells. But Tadalafil, commonly known for treating erectile dysfunction, works differently. It enhances blood flow and might improve the delivery and effectiveness of chemotherapy drugs by dilating blood vessels. Researchers are excited because combining Tadalafil with chemotherapy could potentially make the treatment more effective and tolerable by targeting the tumor environment in a new way. This combination approach could offer a fresh perspective in the fight against stomach cancer, possibly improving patient outcomes.

What evidence suggests that Tadalafil + chemotherapy could be effective for stomach cancer?

Research has shown that Tadalafil, when combined with FLOT chemotherapy, might alter the area around stomach tumors. In this trial, participants will receive Tadalafil alone for 2 weeks, followed by Tadalafil with neoadjuvant FLOT chemotherapy for 8 weeks. This combination could reduce certain markers linked to tumor growth. Early results from ongoing studies suggest that Tadalafil might enhance chemotherapy's effectiveness by reducing specific cells that help tumors evade the immune system. Additionally, chemotherapy alone in similar cases has demonstrated a 40% success rate in shrinking tumors. Overall, combining Tadalafil with chemotherapy could make tumors easier to treat before surgery. ^{1 2 5 6 7}

Who Is on the Research Team?

Junaid Arshad, MD

Principal Investigator

University of Arizona

Are You a Good Fit for This Trial?

Adults with resectable gastric or gastroesophageal junction adenocarcinoma, who haven't had prior treatments for their cancer. They must have a certain level of albumin in the blood, measurable disease by scans, and adequate organ function. Participants should not be pregnant or breastfeeding and must agree to use contraception during the study and for six months after.

Inclusion Criteria

My cancer is in the early to mid stages and is located in my stomach or the junction connecting my stomach and esophagus.

My cancer can be measured on scans taken within the last 28 days.

I am fully active and can carry on all my pre-disease activities without restriction.

Exclusion Criteria

I have received treatment for stomach cancer before.

I haven't taken Tadalafil or similar drugs in the last 28 days.

My cancer has spread to other parts of my body.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Tadalafil Monotherapy

Participants receive Tadalafil alone to assess its effect on MDSCs

2 weeks

1 visit (in-person) for baseline assessments

Combination Treatment

Participants receive Tadalafil in combination with FLOT chemotherapy

8 weeks

Regular visits for chemotherapy administration and monitoring

Surgical Intervention

Surgical removal of the tumor following neoadjuvant treatment

1 week

1 visit (in-person) for surgery

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person) for follow-up assessments

What Are the Treatments Tested in This Trial?

Interventions

• Tadalafil

Trial Overview The trial is testing Tadalafil's effect on immune cells in the tumor environment when given alone and alongside standard chemotherapy (FLOT) before surgery. Patients will take Tadalafil for two weeks then combine it with FLOT for eight weeks, aiming to reduce suppressor cells that can hinder anti-cancer responses.

How Is the Trial Designed?

Group I: Tadalafil + chemotherapy Experimental Treatment 1 Intervention

Subjects will receive Tadalafil monotherapy for 2 weeks followed by Tadalafil in combination with neoadjuvant FLOT chemotherapy for 8 weeks in the window between their cancer diagnosis and surgical intervention.

Who Is Running the Clinical Trial?

University of Arizona

Lead Sponsor

Trials

545

Recruited

161,000+

Published Research Related to This Trial

A 68-year-old male with stage IIIb colon cancer showed a significant response to TS-1/CDDP combined chemotherapy, with a decrease in tumor marker CA19-9 and disappearance of metastatic lesions after three treatment courses.

The therapy not only proved effective for colon cancer but also highlighted the importance of individualizing chemotherapy based on tumor characteristics, such as high DPD activity, and it can be administered at home, improving the patient's quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A case report--TS-1/CDDP combined chemotherapy found effective for metastatic recurrence after operation for colon cancer]. Shimizu, T., Inaba, S., Nakata, M., et al.[2013]

A lower dose of docetaxel (50 mg/m2) combined with 5-FU and cisplatin showed a 40% response rate in patients with metastatic gastric cancer, indicating its efficacy in treating this condition.

While the treatment was associated with significant toxicities, including 68% of patients experiencing grade 3/4 neutropenia, the overall toxicity profile was considered tolerable, suggesting that this lower dose may reduce severe side effects compared to higher doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of low-dose docetaxel/fluorouracil/cisplatin in metastatic gastric carcinoma. Park, SR., Chun, JH., Kim, YW., et al.[2019]

In a phase II trial involving 158 untreated patients with advanced gastric cancer, the combination of docetaxel, cisplatin, and 5-fluorouracil (TCF) showed a significantly higher response rate and longer time to progression compared to docetaxel and cisplatin alone (TC).

While the TCF regimen had greater gastrointestinal toxicity and required more dose reductions, it was still manageable, and no deaths were reported in either treatment group, indicating a favorable safety profile for both regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel in combination for advanced gastric cancer. Ajani, JA.[2019]

Docetaxel-based chemotherapy shows significant promise in advanced gastric cancer, achieving response rates of 55% when combined with cisplatin and 5-fluorouracil, and a median survival of 9 months.

The combination of docetaxel with cisplatin and 5-fluorouracil (TCF) is well tolerated, with manageable hematotoxicity and less gastrointestinal toxicity compared to other regimens, indicating its potential as an effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel-based chemotherapy in the treatment of gastric cancer. Roth, AD., Ajani, J.[2020]

In a phase II study involving 58 patients with advanced gastric cancer, the combination of docetaxel, fluorouracil, and leucovorin (TFL) showed a moderate overall response rate of 26%, with 4 complete and 11 partial responses observed.

The TFL regimen was found to have manageable toxicity, with neutropenia being the most common severe side effect (30% of patients), and no toxic deaths reported, indicating a favorable safety profile for this chemotherapy combination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination docetaxel (Taxotere), fluorouracil, and leucovorin (TFL), as first-line chemotherapy in advanced gastric cancer: a Hellenic Cooperative Oncology Group phase II study. Papakostas, P., Tsavdaridis, D., Kosmidis, P., et al.[2022]

The recommended dose (RD) for the new DXO regimen, which combines docetaxel, capecitabine, and oxaliplatin, was established as 60 mg/m² of docetaxel, 1,000 mg/m² of capecitabine, and 100 mg/m² of oxaliplatin, showing promising efficacy in treating advanced gastric cancer (AGC) with 11 out of 14 patients achieving a partial response.

While the DXO regimen demonstrated substantial activity, it also presented significant toxicities, including neutropenia and diarrhea, which were manageable, indicating that this combination could be a viable alternative to the traditional DCF regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of 3-weekly docetaxel, capecitabine and oxaliplatin combination chemotherapy in patients with previously untreated advanced gastric cancer. Sym, SJ., Ryu, MH., Kang, HJ., et al.[2018]

TS-1, an oral formulation of 5-fluorouracil, combined with low-dose cisplatinum (CDDP), showed promising efficacy in treating advanced gastric cancer, with three cases demonstrating significant improvement in symptoms and disease status.

The combination therapy was well tolerated, with only mild adverse reactions reported, suggesting it could be a safe treatment option for patients with advanced gastric cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Three cases of advanced gastric cancer treated by TS-1 in combination with low-dose cisplatinum]. Gomi, T., Ohtoshi, M., Tamaki, N., et al.[2013]

In a phase I study involving 20 patients with upper gastrointestinal malignancies, the combination of docetaxel, cisplatin, and bolus 5-FU was found to have a maximally tolerated dose, with significant toxicities including neutropenia and sepsis leading to two treatment-related deaths.

The treatment regimen showed some efficacy, with three partial responses observed, indicating potential benefits for patients with esophagogastric and gastric cancers, but also highlighting the need for strategies to enhance tolerance to the combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I study of docetaxel, Cisplatin, 5-Fluorouracil and leucovorin. Mulcahy, MF., Loehrer, PJ., Meropol, NJ., et al.[2018]

A weekly formulation of the DCF chemotherapy regimen showed modest efficacy in treating locally advanced and metastatic gastric cancer, with a disease control rate of 57.8% among 64 patients studied.

The weekly DCF regimen resulted in minimal severe hematologic toxicity, making it a safer alternative for patients with lower performance status who cannot tolerate the standard every-three-weeks DCF treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and tolerability of weekly docetaxel, cisplatin, and 5-fluorouracil for locally advanced or metastatic gastric cancer patients with ECOG performance scores of 1 and 2. Turkeli, M., Aldemir, MN., Cayir, K., et al.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05709574

Tadalafil Effect + Chemotherapy in Resectable Gastric/GEJ ... The goal of this clinical trial is to assess the ability of Tadalafil alone and in combination with neoadjuvant FLOT (5-Fluorouracil, Oxaliplatin, and ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.e16104

Modifying the gastric tumor microenvironment with tadalafil Conclusions: Preliminary data of this ongoing study show that tadalafil treatment combined with FLOT, has the potential to decrease SLFN12L+ ...

3. withpower.com withpower.com/trial/phase-2-adenocarcinoma-2-2023-80d3a

Tadalafil + Chemotherapy for Stomach Cancer A lower dose of docetaxel (50 mg/m2) combined with 5-FU and cisplatin showed a 40% response rate in patients with metastatic gastric cancer, indicating its ...

4. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-00400

Tadalafil in Combination with FLOT Chemotherapy prior to ... Tadalafil in combination with chemotherapy may change the size of cancer tumors as well as the tumor microenvironment prior to surgery. Eligibility Criteria ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12378129/

Impact of adjuvant therapy on outcomes of cancer of the ... Median overall survival (OS) and tumor specific survival (TSS) were 19.4 ± 2.9 and 19.9 ± 3.1 months, respectively. 84.4% completed all cycles ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5931815/

selective PDE5 inhibitors as anti-cancer agents Results showed no significant effect on primary tumour growth or on metastatic spread when compared to controls. Pernkopf et al. [16] later showed that ...

7. nature.com nature.com/articles/s42003-025-07519-9

Repurposing of phosphodiesterase-5 inhibitor sildenafil as ... The results indicated that sildenafil exhibited a lower IC50 value and a higher apoptosis rate compared to tadalafil and vardenafil in GC cells ...