CA-4948 + Chemotherapy/Immunotherapy for Stomach & Esophageal Cancer
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Washington University School of Medicine
Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers
Disqualifiers: Other malignancy, Organ transplant, others
No Placebo Group
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This is a phase I trial of CA-4948 in combination with FOLFOX/PD-1 inhibitor with or without trastuzumab for unresectable gastric, GEJ, and esophageal cancer. During the Dose Escalation portion of the study, different dose levels of CA-4948 in combination with FOLFOX/nivolumab will be evaluated by BOIN algorithm.
Dose Expansion will include Cohorts A and B. Expansion Cohort A will enroll up to 12 patients with HER2 negative gastric, GEJ, and esophageal cancer at the expansion dose of CA-4948 determined during Dose Escalation and will use the same treatment regimen of FOLFOX/nivolumab. Expansion Cohort B will investigate CA-4948 at the dose determined during Dose Escalation in combination with FOLFOX/pembrolizumab and trastuzumab in up to 12 patients with HER2 positive disease; however, the initial 6 patients will be considered safety lead-in to confirm the safety and tolerability of this combination; if determined to be safe, an additional 6 patients will be enrolled for a total of 12 in Cohort B.
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. However, you must not be using alternative, holistic, or botanical formulations for cancer treatment, and certain HIV medications may be contraindicated due to drug interactions. It's best to discuss your current medications with the trial team.
What data supports the effectiveness of the drugs used in the CA-4948 + Chemotherapy/Immunotherapy trial for stomach and esophageal cancer?
Research shows that 5-Fluorouracil (5-FU) combined with folinic acid (leucovorin) or interferon has shown higher remission rates in gastric cancer compared to 5-FU alone. In esophageal cancer, 5-FU combined with interferon resulted in a 27% remission rate in a study, indicating it may be more effective than 5-FU alone.
12345Is the combination of CA-4948 and chemotherapy/immunotherapy safe for humans?
The safety of 5-fluorouracil (5-FU) and its combinations with leucovorin (a form of folic acid) has been studied in patients with colorectal and gastric cancer, showing it can be used safely in these conditions. However, specific safety data for CA-4948 combined with these treatments in stomach and esophageal cancer is not provided in the available research.
678910What makes the drug CA-4948 combined with chemotherapy/immunotherapy unique for stomach and esophageal cancer?
This treatment is unique because it combines CA-4948, a novel drug, with established chemotherapy and immunotherapy agents like 5-FU, Leucovorin, Oxaliplatin, Nivolumab, and Pembrolizumab, potentially enhancing the effectiveness of standard treatments for stomach and esophageal cancer.
12111213Eligibility Criteria
Adults with advanced, inoperable or metastatic stomach, gastroesophageal junction, or esophageal cancer. They must not have had previous systemic treatment for their cancer and should be in good physical condition (ECOG 0-1). Participants need normal organ and bone marrow function and known HER2 status. Women of childbearing potential and men must agree to use contraception.Inclusion Criteria
I had palliative radiation therapy over 10 days ago.
I am 18 years old or older.
My bone marrow and organs are functioning normally.
+11 more
Exclusion Criteria
I am not on any experimental drugs, or it has been 7 days since my last dose.
I have an autoimmune disease.
I have not received a live vaccine in the last 30 days.
+14 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Dose Escalation
Different dose levels of CA-4948 in combination with FOLFOX/nivolumab are evaluated using the BOIN algorithm
14 months
Every 14 days
Dose Expansion
Expansion Cohorts A and B receive CA-4948 at the dose determined during Dose Escalation with FOLFOX/nivolumab or FOLFOX/pembrolizumab and trastuzumab
14 months
Every 14 days
Follow-up
Participants are monitored for safety and effectiveness after treatment
6 months
Participant Groups
The trial is testing CA-4948 combined with FOLFOX chemotherapy and a PD-1 inhibitor (nivolumab or pembrolizumab), with an additional option of trastuzumab for those with HER2 positive disease. It includes dose escalation to find the safest dose followed by expansion cohorts based on HER2 status.
3Treatment groups
Experimental Treatment
Group I: Dose Expansion Cohort B (CA4948 + FOLFOX + Pembrolizumab + Trastuzumab)Experimental Treatment4 Interventions
* CA4948 (dose will be the recommended dose found in the dose escalation portion of study) twice daily by mouth Standard of care mFOLFOX7 every 14 days. Pembrolizumab on day 1 of every 3 cycles. Trastuzumab every 14 days.
* Each cycle is 14 days.
Group II: Dose Expansion Cohort A (CA4948 + FOLFOX + Nivolumab)Experimental Treatment3 Interventions
* CA4948 (dose will be the recommended phase II dose found in the dose escalation portion of study) twice daily by mouth. Standard of care mFOLFOX7 every 14 days. Nivolumab every 14 days.
* Each cycle is 14 days.
Group III: Dose Escalation (CA4948 + FOLFOX + Nivolumab)Experimental Treatment3 Interventions
* CA4948 (dose will depend on dose level assigned) twice daily by mouth. Standard of care mFOLFOX7 every 14 days. Nivolumab every 14 days.
* Each cycle is 14 days.
5-FU is already approved in United States, European Union, Canada, Japan for the following indications:
🇺🇸 Approved in United States as Fluorouracil for:
- Colorectal cancer
- Breast cancer
- Stomach cancer
- Pancreatic cancer
🇪🇺 Approved in European Union as Fluorouracil for:
- Colorectal cancer
- Breast cancer
- Stomach cancer
- Pancreatic cancer
- Skin cancer
🇨🇦 Approved in Canada as Fluorouracil for:
- Colorectal cancer
- Breast cancer
- Stomach cancer
- Pancreatic cancer
🇯🇵 Approved in Japan as Fluorouracil for:
- Colorectal cancer
- Breast cancer
- Stomach cancer
- Pancreatic cancer
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Washington University School of MedicineSaint Louis, MO
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Who Is Running the Clinical Trial?
Washington University School of MedicineLead Sponsor
The Foundation for Barnes-Jewish HospitalCollaborator
Curis, Inc.Industry Sponsor
References
Biochemical modulation of 5-fluorouracil by folinic acid or alpha-interferon with and without other cytostatic drugs in gastric, esophageal, and pancreatic cancer. [2018]5-Fluorouracil (5-FU) is one of the important antineoplastic agents for the treatment of gastrointestinal cancers. The biochemical modulation of 5-FU by various drugs has brought about the two combinations of 5-FU/folinic acid (FA) and 5-FU/alpha-interferon (IFN), which have shown clinical activity in phase II and III trials, especially in colorectal cancer. The experience with both combinations in upper gastrointestinal cancers, however, is limited. In esophageal cancer, two phase II studies with 5-FU/IFN reported seven (27%) objective remissions in 26 patients, indicating superiority of 5-FU/IFN over 5-FU monotherapy. Trials with 5-FU/FA alone are lacking in esophageal cancer. The modulation of 5-FU by IFN or FA failed to show clinically significant activity in pancreatic cancer. However, in gastric cancer, 5-FU/FA and 5-FU/IFN seem to induce higher complete and overall remission rates in advanced gastric cancer compared with 5-FU alone. With the daily times five schedule of 5-FU/FA, 27% objective remissions were achieved; in combination with other cytotoxic drugs, such as etoposide, anthracyclines, cisplatin, mitomycin, or methotrexate, objective response rates up to 50% and more were reported.
S-1 for the treatment of gastrointestinal cancer. [2022]5-Fluorouracil (5-FU)-based regimens are used worldwide as the standard treatment in chemotherapy for gastric cancer. S-1 , a fourth-generation oral fluoropyrimidine that combines tegafur and two biochemical modulators: gimeracil and oteracil potassium, is now attracting considerable interest.
Randomized trial comparing epirubicin, cisplatin, and fluorouracil versus fluorouracil, doxorubicin, and methotrexate in advanced esophagogastric cancer. [2022]We report the results of a prospectively randomized study that compared the combination of epirubicin, cisplatin, and protracted venous infusion fluorouracil (5-FU) (ECF regimen) with the standard combination of 5-FU, doxorubicin, and methotrexate (FAMTX) in previously untreated patients with advanced esophagogastric cancer.
Doxifluridine as palliative treatment in advanced gastric and pancreatic cancer patients. [2018]The association of 5-fluorouracil (5-FU) and leucovorin is currently the most used combination in the treatment of advanced gastrointestinal neoplasms. Doxifluridine (d-FUR) is a fluoropyrimidine derivative that is converted into 5-FU inside tumor cells, where it is selectively cytotoxic. The oral administration of dFUR has been extensively investigated in colorectal carcinoma, and has been proven to be active and well tolerated. The purpose of this study was to test the effectiveness of the oral combination with dFUR plus l-leucovorin in gastric and pancreatic cancer patients.
Phase II trial of neoadjuvant cisplatin, 5-fluorouracil and interferon-alpha in operable squamous cell carcinoma of the esophagus. [2013]The combination of 5-fluorouracil (5-FU), cisplatin and interferon (IFN)-alpha was found to result in a high response rate in advanced esophageal squamous cell carcinoma (SCC).
Adjuvant therapy with oral fluoropyrimidines as main chemotherapeutic agents after curative resection for colorectal cancer: individual patient data meta-analysis of randomized trials. [2019]Oral 5-fluorouracil and its prodrugs (tegafur, carmofur) is now being studied for adjuvant chemotherapy of curatively resected colorectal cancers. To evaluate the effect of these oral fluoropyrimidines (o-FPs), an individual patient data (IPD) meta-analysis of randomized clinical trials was performed in Japan as an inter-trialist group study.
Second-line treatment of advanced colorectal cancer with a weekly simultaneous 24-hour infusion of 5-fluorouracil and sodium-folinate: a multicentre phase II trial. [2013]A weekly continuous 24-h infusion therapy with 5-fluorouracil (5-FU) preceded by a 2-h infusion of calcium folinate (CA-FA) was shown to be an effective first- and secondline treatment in advanced metastatic colorectal cancer. Substitution of CA-FA by the new formulation sodium folinate (S-FA) allows the simultaneous i.v. administration of folinic acid with 5-FU in one pump.
Phase II study of a weekly 24-hour infusion with 5-fluorouracil and simultaneous sodium-folinic acid in the first-line treatment of metastatic colorectal cancer. [2017]A weekly continuous 24-hour infusion therapy with 5-fluorouracil (5-FU) and calcium - folinic acid (CA-FA) was shown to be an effective first-line treatment in advanced metastatic colorectal cancer. Sodium - folinic acid (S-FA) is a new formulation which, in contrast to CA-FA allows the simultaneous i.v. administration in combination with 5-FU in one pump.
Randomized, open-label, phase III study of a 28-day oral regimen of eniluracil plus fluorouracil versus intravenous fluorouracil plus leucovorin as first-line therapy in patients with metastatic/advanced colorectal cancer. [2017]To compare the efficacy and tolerability of eniluracil (EU)/fluorouracil (5-FU) with that of 5-FU/leucovorin (LV) as first-line therapy for patients with metastatic/advanced colorectal cancer.
A phase II and pharmacokinetic study of first line S-1 for advanced gastric cancer in Taiwan. [2022]To evaluate the efficacy, safety and pharmacokinetic profiles of S-1, which composed of tegafur (FT, a prodrug of 5-FU), 5-chloro-2,4-dihydroxypyridine and potassium oxonate (Oxo), in Taiwanese advanced gastric cancer (AGC) patients.
cDNA microarray analysis of differential gene expression in gastric cancer cells sensitive and resistant to 5-fluorouracil and cisplatin. [2021]Gastric cancer is one of the most prevalent cancers worldwide. 5-fluorouracil (5-FU) and cisplatin are the most commonly used drugs for the treatment of gastric cancer. However, a significant number of tumors often fail to respond to chemotherapy.
Capecitabine in the treatment of esophageal and gastric cancers. [2015]Fluoropyrimidine therapy has been a mainstay in the treatment of cancers of the esophagus and stomach for nearly half of a century in the form of intravenous 5-fluorouracil. Capecitabine , an oral fluoropyrimidine precursor, was first approved in 2001 for the treatment of metastatic colon cancer and may be used interchangeably with parenteral 5-FU in the treatment of upper gastrointestinal (GI) cancers.
Pharmacogenomics of fluorouracil -based chemotherapy toxicity. [2015]5- fluorouracil (5-FU), alone or in combination, is the most prevalent and effective chemotherapeutic agent for the treatment of cancers of the head and neck, breast, pancreas and gastrointestinal tract.