A Phase I Study of Anetumab Ravtansine in Combination With Either Anti-PD-1 Antibody, or Anti-CTLA4 and Anti-PD-1 Antibodies or Anti-PD-1 Antibody and Gemcitabine in Mesothelin-Positive Advanced Pancreatic Adenocarcinoma
Phase 1 trial tests new combination therapy for advanced pancreatic cancer
Plain English Summary
Testing the Combination of Anetumab Ravtansine With Either Nivolumab, Nivolumab and Ipilimumab, or Gemcitabine and Nivolumab in Advanced Pancreatic Cancer is a Phase 1 clinical trial sponsored by National Cancer Institute (NCI) studying Pancreatic Adenocarcinoma, Stage II Pancreatic Cancer AJCC v8, Stage III Pancreatic Cancer AJCC v8, Stage IV Pancreatic Cancer AJCC v8. This trial tests a combination of drugs, including anetumab ravtansine, nivolumab, ipilimumab, and gemcitabine, to see how safe and effective they are in treating advanced pancreatic cancer. It is for patients with pancreatic cancer that has spread and has a specific protein called mesothelin on its surface. Participation involves receiving the study drugs, undergoing regular medical check-ups, and providing tumor tissue samples for analysis. Standard chemotherapy or other cancer treatments are the current alternatives for patients with advanced pancreatic cancer. The trial aims to enroll 74 participants.
Official Summary
This phase I trial studies the side effects and best dose of anetumab ravtansine when given together with nivolumab, ipilimumab and gemcitabine hydrochloride in treating patients with mesothelin positive pancreatic cancer that has spread to other places in the body (advanced). Anetumab ravtansine is a monoclonal antibody, called anetumab ravtansine, linked to a chemotherapy drug called DM4. Anetumab attaches to mesothelin positive cancer cells in a targeted way and delivers DM4 to kill them. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving anetumab ravtansine together with nivolumab, ipilimumab, and gemcitabine hydrochloride may work better in treating patients with pancreatic cancer.
Who Can Participate
Here is what you need to know about eligibility for this trial. Patients must be at least 18 years old and have a confirmed diagnosis of pancreatic cancer that has spread or cannot be removed by surgery. The cancer must show a specific marker called mesothelin on its cells. Patients should have a life expectancy of at least 3 months and be in good general health (ECOG score 0-1). Patients must have received at least one prior cancer treatment and their cancer has progressed or they could not tolerate the treatment. This trial is studying Pancreatic Adenocarcinoma, Stage II Pancreatic Cancer AJCC v8, Stage III Pancreatic Cancer AJCC v8, Stage IV Pancreatic Cancer AJCC v8, so participants generally need a confirmed diagnosis.
What They're Measuring
The primary outcome measures the maximum tolerated dose, which helps determine the safest and most effective dose of the study drugs for future trials. The specific primary outcome measures are: Maximum tolerated dose (MTD) (Up to 30-37 days post treatment). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.
About This Phase
This trial is in Phase 1, the first major stage of clinical testing. Phase 1 trials typically involve 20-100 participants and focus on safety, dosage levels, and side effects. The primary goal is not to test whether the treatment works but to establish that it is safe enough for further testing. About 70% of Phase 1 drugs advance to Phase 2. If successful, the treatment will proceed to Phase 2 efficacy testing.
Why This Trial Matters
This trial aims to fill a treatment gap by exploring a novel combination therapy for advanced pancreatic cancer, a disease with limited effective treatment options. This research targets Pancreatic Adenocarcinoma, Stage II Pancreatic Cancer AJCC v8, Stage III Pancreatic Cancer AJCC v8, Stage IV Pancreatic Cancer AJCC v8, where improved treatment options are needed.
Investor Insight
This Phase 1 trial is an early step in evaluating a new treatment approach for a difficult-to-treat cancer, with potential for future market entry if successful. Phase 1 trials have approximately a 10% chance of eventually gaining FDA approval.
Is This Trial Right for Me?
Ask your doctor about the specific drugs being tested, potential side effects, and how the study drugs will be administered. Be prepared for regular clinic visits for drug infusions, blood tests, and imaging scans to monitor your health and cancer. You will need to provide tumor tissue samples, which may involve additional biopsies. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.
AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.
Study Design
- Study Type: INTERVENTIONAL
- Allocation: NON_RANDOMIZED
- Model: PARALLEL
- Masking: NONE
- Enrollment: 74 participants
Interventions
- BIOLOGICAL: Anetumab Ravtansine — Given IV
- PROCEDURE: Biopsy Procedure — Undergo biopsy
- PROCEDURE: Biospecimen Collection — Undergo collection of blood
- DRUG: Gemcitabine Hydrochloride — Given IV
- BIOLOGICAL: Ipilimumab — Given IV
Primary Outcomes
- Maximum tolerated dose (MTD) (Up to 30-37 days post treatment)
Secondary Outcomes
- Biomarker analysis (Up to 100 days post treatment)
Full Eligibility Criteria
Inclusion Criteria:
* Patients must have histologically or cytologically confirmed pancreatic adenocarcinoma that is metastatic or unresectable or recurrent
* Only subjects with positive mesothelin expression (Ventana mesothelin \[MSLN\]- immunohistochemistry \[IHC\]; Negative=H-score =\< 10) are eligible. This is to be performed centrally. For dose escalation cohorts, patients with mesothelin expression in \>= 5% of tumor cells are eligible. For dose expansion, patients must have moderate or strong tumor mesothelin expression defined as \>= 30% of tumor cells with mesothelin expression of 2+/3 on immunohistochemical staining
* Patients must be \>= 18 years of age
* Patients must have received and either progressed or been intolerant to at least 1 systemic therapy
* Life expectancy of at least 3 months
* Eastern Cooperative Oncology Group (ECOG) performance status score 0-1 (Karnofsky \>= 80%)
* Prior anti-cancer treatments are permitted (i.e. chemotherapy, including gemcitabine and nab-paclitaxel; radiotherapy; hormonal, or immunotherapy with the exception of anti-CTLA4, anti-PD1/PD-L1, and combination of anti-CTLA4 and anti-PD1/PD-L1) providing toxicity (except for alopecia) related to prior anti-cancer therapy and/or surgery have either resolved, improved to baseline or G1
* At least one (1) measurable lesion at baseline by computed tomography (CT) or magnetic resonance imaging (MRI) as per RECIST version (v)1.1; measurable disease is a requirement in both dose escalation phase and dose expansion phase
* Note: Measurable lesions may be in an irradiated field as long as there is documented progression and the lesion(s) can be reproducibly measured
* At least one lesion safely accessible for biopsy unless medically contraindicated; biopsies are mandatory both in dose escalation and in dose expansion; in dose escalation and in expansion the following biopsies are optional: at baseline and at progression; biopsy could be: core needle or excisional or punch biopsy. Irradiated lesions can be biopsied if tumor growth is confirmed
* Patients must have archival tumor tissue for mesothelin expression and correlative biomarker studies; subjects must consent to provide tumor blocks or slides and the availability of the tissue must be confirmed prior to subjects receiving study medication; if an archived tumor specimen is unavailable or unsuitable for correlative biomarker studies, a pre-treatment fresh tumor biopsy is required
* Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin \[HCG\]) within 24 hours of study enrollment or randomization; WOCBP must agree to appropriate methods of contraception for the duration of treatment and for 6 months after completion of treatment; males who are sexually active with a partner of childbearing potential must agree to appropriate methods of contraception for the duration of treatment. For all male patients, prior to treatment, advice should be sought for conserving sperm due to the chance of irreversible infertility as a consequence of treatment; genetic consultation is recommended if the patient wishes to have children after ending treatment; the investigator or a designated associate is requested to advise the patient how to achieve highly effective birth control
* Highly effective (failure rate of less than 1% per year) contraception methods include:
* Combined (estrogen and progesterone containing: oral, intravaginal, transdermal) and progesterone-only (oral, injectable, implantable) hormonal contraception associated with inhibition of ovulation
* Intrauterine device (IUD) or intrauterine hormone-releasing system (IUS)
* Bilateral tubal occlusion or vasectomized partner (provided that partner is the sole sexual partner and has received medical assessment of the surgical success)
* Sexual abstinence (reliability to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient)
* Male patients with a female partner of childbearing potential must use a condom and ensure that an additional form of contraception is also used during
* Note: a woman is considered WOCBP, i.e. fertile, following menarche and until becoming postmenopausal unless permanently sterile; permanent sterilization methods include but are not limited to hysterectomy, bilateral salpingectomy and bilateral oophorectomy
* A postmenopausal state is defined as no menses for 12 months without an alternative medical cause; a high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy; a man is considered fertile after puberty unless permanently sterile by bilateral orchiectomy
* Leukocytes \>= 3,000/mcL
* Absolute neutrophil count (ANC) \>= 1,500/mcL
* Platelets \>= 100,000/mcL
* Trial Locations
- University of Alabama at Birmingham Cancer Center, Birmingham, Alabama, United States
- City of Hope Comprehensive Cancer Center, Duarte, California, United States
- City of Hope at Irvine Lennar, Irvine, California, United States
- Keck Medicine of USC Koreatown, Los Angeles, California, United States
- Los Angeles General Medical Center, Los Angeles, California, United States
- USC / Norris Comprehensive Cancer Center, Los Angeles, California, United States
- UC Irvine Health/Chao Family Comprehensive Cancer Center, Orange, California, United States
- University of California Davis Comprehensive Cancer Center, Sacramento, California, United States
- UCHealth University of Colorado Hospital, Aurora, Colorado, United States
- UM Sylvester Comprehensive Cancer Center at Coral Gables, Coral Gables, Florida, United States
- ...and 10 more locations
Frequently Asked Questions
What is clinical trial NCT03816358?
NCT03816358 is a Phase 1 INTERVENTIONAL study titled "Testing the Combination of Anetumab Ravtansine With Either Nivolumab, Nivolumab and Ipilimumab, or Gemcitabine and Nivolumab in Advanced Pancreatic Cancer." It is currently active, not recruiting and is sponsored by National Cancer Institute (NCI). The trial targets enrollment of 74 participants.
What conditions does NCT03816358 study?
This trial investigates treatments for Pancreatic Adenocarcinoma, Stage II Pancreatic Cancer AJCC v8, Stage III Pancreatic Cancer AJCC v8, Stage IV Pancreatic Cancer AJCC v8. The primary condition under study is Pancreatic Adenocarcinoma.
What treatments are being tested in NCT03816358?
The interventions being studied include: Anetumab Ravtansine (BIOLOGICAL), Biopsy Procedure (PROCEDURE), Biospecimen Collection (PROCEDURE), Gemcitabine Hydrochloride (DRUG), Ipilimumab (BIOLOGICAL). Given IV
What does Phase 1 mean for NCT03816358?
Phase 1 trials are the first stage of testing a new treatment in humans. They focus on safety, dosage, and side effects, usually involving 20-100 healthy volunteers or patients.
What is the current status of NCT03816358?
This trial is currently "Active, Not Recruiting." It started on 2019-12-09. The estimated completion date is 2027-01-31.
Who is sponsoring NCT03816358?
NCT03816358 is sponsored by National Cancer Institute (NCI). The sponsor is responsible for funding, designing, and overseeing the clinical trial.
How many people can participate in NCT03816358?
The trial aims to enroll 74 participants. The trial status is active, not recruiting.
How is NCT03816358 designed?
This is a interventional study, uses non_randomized allocation, follows a parallel design, employs none masking.
What are the primary outcomes being measured in NCT03816358?
The primary outcome measures are: Maximum tolerated dose (MTD) (Up to 30-37 days post treatment). These are the main endpoints researchers use to determine whether the treatment is effective.
Where is NCT03816358 being conducted?
This trial is being conducted at 20 sites, including Birmingham, Alabama; Duarte, California; Irvine, California; Los Angeles, California and 16 more sites (United States).
Where can I find official information about NCT03816358?
The official record for NCT03816358 is available on ClinicalTrials.gov at https://clinicaltrials.gov/study/NCT03816358. This government database provides the most up-to-date and detailed information about the trial.
What is NCT03816358 testing in simple terms?
This trial tests a combination of drugs, including anetumab ravtansine, nivolumab, ipilimumab, and gemcitabine, to see how safe and effective they are in treating advanced pancreatic cancer. It is for patients with pancreatic cancer that has spread and has a specific protein called mesothelin on its surface.
Why is this trial significant?
This trial aims to fill a treatment gap by exploring a novel combination therapy for advanced pancreatic cancer, a disease with limited effective treatment options.
What are the potential risks of participating in NCT03816358?
Common side effects may include fatigue, nausea, vomiting, diarrhea, and skin reactions. More serious side effects can occur, including liver problems, nerve damage, and effects on blood cell counts. The study drugs may also affect your immune system, potentially leading to autoimmune reactions. As with any clinical trial, participants are closely monitored and can withdraw at any time.
Should I consider participating in NCT03816358?
Ask your doctor about the specific drugs being tested, potential side effects, and how the study drugs will be administered. Be prepared for regular clinic visits for drug infusions, blood tests, and imaging scans to monitor your health and cancer. You will need to provide tumor tissue samples, which may involve additional biopsies. Always discuss clinical trial participation with your healthcare provider to determine if it is appropriate for your specific situation.
What does NCT03816358 signal from an investment perspective?
This Phase 1 trial is an early step in evaluating a new treatment approach for a difficult-to-treat cancer, with potential for future market entry if successful. This is a Phase 1 trial, which is in early development stages.
What happens if the treatment in this trial doesn't work?
Participation involves receiving the study drugs, undergoing regular medical check-ups, and providing tumor tissue samples for analysis. Participants in clinical trials always have the right to withdraw and pursue alternative treatments. The study team will help transition patients to other available options.
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This analysis is AI-generated and does not constitute medical advice. Always consult your healthcare provider before making decisions about clinical trial participation.