Colorectal CancerPhase 1/2NCT07411599
Dual Administration Of Intraperitoneal And Intravenous TROP2-Directed CAR-NK With TGF-Beta Receptor 2 (TGFBR2) Knock Out (KO) Therapy For Colorectal Cancer-Related Peritoneal Carcinomatosis: A Phase 1/2 Trial ("Chip-CRC Trial")
A Phase 1/2 study testing Cyclophosphamide, Fludarabine and Cetuximab in people with Colorectal Cancer and Peritoneal Metastases, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
To find the highest dose of NK cells that can be given by vein and intraperitoneally (given directly into the abdominal cavity) in combination with cetuximab to patients with colorectal cancer that has spread to the peritoneum. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer, Peritoneal Metastases, Carcinomatosis
- What is being tested?
- Cyclophosphamide, Fludarabine and Cetuximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 1 siteUnited States
- Study dates
- 20 Apr 2026to 15 Nov 2030
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- Pregnant, breastfeeding, or expecting to conceive within the projected duration of the study, starting with screening visit through 4 months after last dose of trail treatment (TROP2 CAR/IL-15 TGFBR2 KO NK cell therapy). If a WOCBP has a positive urine pregnancy test within 72 hours prior to administration of LD chemotherapy that cannot be confirmed as negative, a serum pregnancy test will be required.
- Participants with BRAFV600E mutated tumors (determined by Next Generation Sequencing, NGS) will be excluded.
- Has received systemic anti-cancer therapy within 4 weeks of their scheduled diagnostic laparoscopy (DL)/IP catheter placement or 6 weeks if the regimen included Bevacizumab. Or has received systemic chemotherapy of any kind within 4 weeks prior to the time of their lymphodepleting (LD) chemotherapy.
- Participants must have recovered from all AEs due to previous therapies to Grade ≤1 or baseline. Participants with Grade ≤2 neuropathy, alopecia, or other AEs may be deemed eligible at the discretion of the PI. If a participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment.
- Has received prior radiotherapy within 2 weeks of the start of study intervention (DL). Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout if permitted for palliative radiation (≤2 weeks of radiotherapy) to non-central nervous system (CNS) disease.
- Has received a live vaccine within 30 days prior to the initiation of LD chemotherapy. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus-Calmette-Guérin (BCG), and typhoid vaccines. Seasonal influenza and COVID vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g. FluMist®) are live attenuated vaccines and are not allowed.
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- Is currently receiving another investigational agent or has used an investigational device within 6 weeks prior to the first dose of study intervention. Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 6 weeks after the last dose of the previous investigation agent.
- Diagnosis of immunodeficiency or receiving chronic systemic steroid therapy (in dosing exceeding 10mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose LD.
- High-volume extra-peritoneal visceral metastases to include but are not limited to, high volume (>3) liver metastases, high volume (>5) lung metastases, CNS metastases (any number) and/or carcinomatous meningitis, bone metastases (any number) will be excluded. Any participant s with >8 total metastases combined between all visceral extraperitoneal sites will also be excluded. Low volume liver (≤3) and/or lung (≤5) metastases that have been treated, are amendable to locoregional therapy, and are not an immediate threat to life may be included at the discretion of the PI if the total number of visceral extraperitoneal metastases remains ≤ 8. Individuals with nodal metastases and/or abdominal wall metastases similarly may be included at the discretion of the PI.
- Active autoimmune disease that has required systemic treatment in the past 2 months (i.e. with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is allowed.
- History of interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
- Serious active infection requiring intravenous systemic therapy.
- Uncontrolled Human Immunodeficiency Virus (HIV) infection. Participants with HIV who have an undetectable viral load and a CD4 count of at least 400 cells/mm3 may participate.
- Known Hepatitis B Virus (HBV) not on suppressive therapy or with detectable viral load on suppressive therapy. If undetectable viral load on suppressive therapy, OK to participate.
- Known Hepatitis C Virus who has not been treated or cured, or who is currently being treatment with a detectable viral load. If cured or being treated with an undetectable viral load, OK to participate.
- Known history of active Tuberculosis (TB).
- History or current evidence of any condition, therapy, or laboratory abnormalities that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
- Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- Has had allogeneic tissue/solid organ transplant.
- Clinically significant cardiovascular disease within 12 months from the first dose of study intervention, including New York Heart Association (NYHA) Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular event, or cardiac arrhythmia associated with hemodynamic instability. Note: medically controlled arrhythmia would be permitted.
- Prolonged QTcF interval to >480 ms.
- Bleeding or thrombotic disorders or subjects at risk of severe hemorrhage. Subject with known deep vein thrombosis/pulmonary embolism that are under appropriate anticoagulation treatment are eligible.
- Radiographic distribution of disease that in the investigator's opinion would impart excessive risk to participation to this protocol.
- Active peritonitis or diverticulitis.
- Medical or surgical history that in the treating physician's opinion would make the subject not a suitable candidate for intraperitoneal therapy. Examples would include surgically documented extensive intraperitoneal adhesions, prior HIPEC operation, or large volume ascites.
- History of severe hypersensitivity reaction with biologic therapies (e.g. monoclonal antibodies).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
MD Anderson Cancer Center
Houston, Texas, 77030
Paula M Smith, MD, 713-792-3785, psmith7@mdanderson.org
Paula M Smith, MD
About this study
To find the highest dose of NK cells that can be given by vein and intraperitoneally (given directly into the abdominal cavity) in combination with cetuximab to patients with colorectal cancer that has spread to the peritoneum.
Read the detailed description
Primary Objective and Endpoints Objective: Determine the safety, and Maximum Tolerated Dose (MTD), Recommended Phase 2 Dose (RP2D), schedule of iterative delivery of dual administration of IP/IV TROP2 CAR/IL-15 TGFBR2 KO NK cells Cell Therapy + IV Cetuximab
- Conditions
- Colorectal Cancer, Peritoneal Metastases, Carcinomatosis
- Being tested
- Cyclophosphamide, Fludarabine, Cetuximab, NK Cells
- Keywords
- Trop2, CAR-NK, Phase 1/2, TGfBR2
- Medical subject headings
- Colorectal Neoplasms, Carcinoma, Colorectal Cancer, Hereditary Nonpolyposis, Type 6
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CyclophosphamideDrug
Given by IV
FludarabineDrug
Also called Fludara
Given by IV
CetuximabDrug
Also called Erbitux
Given by IV
NK CellsDrug
Given by IV and IP
| Study group | Role | What they receive |
|---|---|---|
| Dose Escalation | Experimental | To find the highest dose of NK cells that can be given by vein and intraperitoneally (given directly into the abdominal cavity) in combination with cetuximab to patients with colorectal cancer that has spread to the peritoneum. Receives: Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Cetuximab; Drug: NK Cells |
| Dose Expansion | Experimental | To learn if the recommended dose of NK cells found in Phase 1 given by vein and intraperitoneally in combination with cetuximab can help to control the disease. Receives: Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Cetuximab; Drug: NK Cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and adverse events (AEs
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
Measured: Through study completion; an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
20 Apr 202615 Nov 2030
- First posted17 Feb 2026
- Study start20 Apr 2026
- Primary completion15 Nov 2028 (estimated)
- Study completion15 Nov 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 28 participants (estimated)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Paula M Smith, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07411599
- Sponsor's protocol ID
- 2025-1617
- Other IDs
- NCI-2026-00995
- Status last verified
- Sep 2026
- First submitted
- 9 Feb 2026
- Last updated
- 5 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No