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")

NCT07411599 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 2025-1617NCI-2026-00995
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Colorectal Cancer; Peritoneal Metastases; Carcinomatosis

Keywords

Trop2; CAR-NK; Phase 1/2; TGfBR2

Outcome Measures

Primary Outcomes (1)

• 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

  Through study completion; an average of 1 year

Study Arms (2)

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.

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.

Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Cetuximab; Drug: NK Cells

Interventions

Cyclophosphamide DRUG

Given by IV

Dose Escalation; Dose Expansion

Fludarabine DRUG

Given by IV

Also known as: Fludara

Dose Escalation; Dose Expansion

Cetuximab DRUG

Given by IV

Also known as: Erbitux

Dose Escalation; Dose Expansion

NK Cells DRUG

Given by IV and IP

Dose Escalation; Dose Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Colorectal Neoplasms; Carcinoma; Colorectal Cancer, Hereditary Nonpolyposis, Type 6

Interventions

Cyclophosphamide; fludarabine; fludarabine phosphate; Cetuximab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Paula M Smith, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Paula M Smith, MD

CONTACT

713-792-3785; psmith7@mdanderson.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 9, 2026
• First Posted: February 17, 2026
• Study Start: April 20, 2026
• Primary Completion (Estimated): November 15, 2028
• Study Completion (Estimated): November 15, 2030
• Last Updated: April 23, 2026

Record last verified: 2026-04

Locations

US (1)