NIH Clinical Center Search the Studies: Study Number, Study Title

Protocol Details

Phase II Study Evaluating the Efficacy of M9241 in Combination with Hepatic Artery Infusion Pump (HAIP) and Systemic Therapy for Subjects with Metastatic Colorectal Cancer or Intrahepatic Cholangiocarcinoma

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

000307-C

Sponsoring Institute

National Cancer Institute (NCI)

Recruitment Detail

Type: Participants currently recruited/enrolled
Gender: Male & Female
Min Age: 18 Years
Max Age: N/A

Referral Letter Required

No

Population Exclusion(s)

Fetuses;
Pregnant Women;
Children

Keywords

Mcrc;
Icc;
NHS-IL12;
Response Rates;
Progression Free Survival (Pfs);
Overall Survival (Os);
Patient Survival;
Unresectable Liver Tumor;
SMART System

Recruitment Keyword(s)

None

Condition(s)

Metastatic Colorectal Cancer (Mcrc);
Intrahepatic Cholangiocarcinoma (Icc);
Colorectal Cancer;
Colorectal Neoplasms;
Cholangiocarcinoma;
Intrahepatic Bile Duct Cancer;
Bile Duct Cancer;
Bile Duct Neoplasms

Investigational Drug(s)

Floxuridine (FUDR)
5-Fluorouracil (5-FU)

Investigational Device(s)

None

Intervention(s)

Drug: Floxuridine
Drug: 5-Fluorouracil
Drug: Irinotecan
Device: Intera 3000 Hepatic Artery Infusion Pump (HAIP)
Drug: Oxaliplatin
Drug: Leucovorin
Drug: M9241
Drug: Gemcitabine
Drug: Dexamethasone

Supporting Site

National Cancer Institute

Background:

One way to treat liver cancer is to deliver chemotherapy drugs only to the liver (and not to the whole body). Researchers want to see if adding the drug M9241 can improve the treatment. The drug triggers the immune system to fight cancer.<TAB>

Objective:

To see if treatment with HAIPs to deliver liver-directed chemotherapy in combination with M9241 is effective for certain cancers.

Eligibility:

People aged 18 and older who have cancer of the bile ducts that is only in the liver, or colorectal cancer that has spread to the liver.

Design:

Participants will be screened with:

Medical history

Physical exam

Blood tests

Pregnancy test (if needed)

Tumor biopsy (if needed)

Electrocardiogram

Computed tomography (CT) scans

Participants will have an abdominal operation. A catheter will be placed into an artery that feeds blood to the liver. The catheter will then be attached to the HAIP. The HAIP will lay under the skin on the left side of the abdomen.

Participants will have chemotherapy drugs or heparin with saline infused into the HAIP every 2 weeks. M9241 will be injected under the skin every 4 weeks. They will get systemic chemotherapy through an IV or mediport every 2 weeks. They will receive this treatment until their cancer gets worse or they have bad side effects.

Participants will have 2 study visits each month. They will have CT scans every 8 weeks. At visits, they will repeat some screening tests.

Participants will have a follow-up visit 1 month after treatment ends. Then they will be contacted every 6 months for 5 years.

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Eligibility

INCLUSION CRITERIA:

Inclusion Criteria- All Cohorts

-Age >= 18 years.

-Negative serum or urine pregnancy test at screening for women of childbearing potential (WOCBP).

NOTE: WOCBP is defined as any female who has experienced menarche and who has not undergone successful surgical sterilization or who is not postmenopausal. WOCBP must have a negative pregnancy test (HCG blood or urine) during screening

-Women of child-bearing potential and men must agree to use highly effective contraception prior to study entry, for the duration of study participation and for 3 months after completion of study treatment. Highly effective birth control (failure rate of less than 1%), e.g., intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, vasectomized partner and sexual abstinence. The use of condoms by male subjects is required unless the female partner is permanently sterile.

-Breastfeeding subject must agree to discontinue breastfeeding.

-Arterial anatomy on CT angiogram or CT chest, abdomen and pelvis multiphase (i.e., CT C/A/P multiphase) amenable to placement of the HAIP.

-Subject must sign the informed consent form to participate in this study.

-HIV-positive subjects may be considered for this study only if they have an undetectable viral load.

-Subjects must agree to co-enroll on the Surgical Oncology Program s tissue collection protocol 13C0176, Tumor, Normal Tissue and Specimens from Patients Undergoing Evaluation or Surgical Resection of Solid Tumors

-Subject s liver metastases must not be amenable to resection/ablation to No Evidence of Disease (NED) in one stage.

-Subject must be able to tolerate systemic chemotherapy at initiation of study treatment as outlined below (mCRC: FOLFOX or FOLFIRI; ICC: GemOx or FOLFOX).

Inclusion Criteria-Metastatic Colorectal Carcinoma

-Subjects must have histologically or cytologically confirmed diagnosis of colorectal adenocarcinoma metastatic to the liver (Cohort 1)

-Subjects must have measurable liver metastatic disease

-Subjects must have received 1st line systemic chemotherapy

-ECOG performance status <= 1

-Subjects must have adequate organ and marrow function as defined below:

--leukocytes > 3,000/mcL

--absolute neutrophil count > 1,500/mcL

--platelets > 90,000/mcL

--hemoglobin > 8 g/dL

--total bilirubin < 1.5 X institutional upper limit of normal

--AST(SGOT)/ALT(SGPT) < 2.5 X institutional upper limit of normal

--creatinine within normal institutional limits OR eGFR within normal as predicted by the CKD-EPI equation > 60 mL/min/1.73 m2..

Inclusion Criteria-Intrahepatic Cholangiocarcinoma

-Subjects must have histologically or cytologically confirmed diagnosis of intrahepatic cholangiocarcinoma confined to the liver (Cohort 2). Archival tumor sample may be used but if archival tissue is not available or is not adequate, tissue biopsy will be required.

-Clinical or radiographic evidence of metastatic disease to regional (porta hepatis) lymph nodes will be allowed, provided it is amenable to resection.

-Subjects must have radiographically measurable disease

-Disease must be considered unresectable at the time of preoperative evaluation.

-Subjects must have received 1st line systemic chemotherapy

-ECOG performance status <= 1.

-Subjects must have adequate organ and marrow function as defined below:

--leukocytes >= 2,000/ mm(3)

--absolute neutrophil count > 1,500/mcL

--platelets >= 75,000/ mm(3)

--hemoglobin > 8 g/dL

--total bilirubin < 1.5 mg/dl

--creatinine <= 1.5 mg/dl

EXCLUSION CRITERIA:

Exclusion Criteria- All Cohorts

-Subjects who are receiving any other investigational agents.

-Subjects who have previously received rIL-12

-Subjects with active autoimmune diseases, that might deteriorate when receiving an immunostimulatory agent with the exceptions:

-diabetes type I, vitiligo, alopecia, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible;

-subjects requiring hormone replacement with corticosteroids are eligible if the steroids are administered only for the purpose of hormonal replacement and at doses <= 10 mg of prednisone or equivalent per day;

-administration of steroids for other conditions through a route known to result in a minimal systemic exposure (topical, intranasal, intro-ocular, or inhalation) is eligible.

-History of organ transplant, except for transplants that do not require immunosuppression.

-History of or active inflammatory bowel disease (e.g., Crohn s disease, ulcerative colitis).

-Known hypersensitivity or allergic reactions attributed to any compounds of similar chemical or biologic composition to the study medication, such as recombinant IL-12 or other monoclonal antibodies and history of allergic reactions attributed to compounds of similar chemical composition to FUDR or heparin.

-Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke < 6 months prior to enrollment, myocardial infarction < 6 months prior to enrollment, unstable angina, congestive heart failure (>= NYHA III) or serious cardiac arrhythmia requiring medication.

-All conditions associated with significant necrosis of nontumor-bearing tissues.

-Esophageal or gastroduodenal ulcers < 6 months prior to treatment.

-Active ischemic bowel disease.

-Psychiatric illness/social situations that would limit compliance with study requirements.

-Active concurrent malignancies within the last five years other than colorectal primary except basal cell skin carcinoma and thyroid carcinoma.

-Prior radiation to liver.

-Subjects with active Hepatitis B or C infection.

-Significant acute or chronic infections (i.e., tuberculosis) history of exposure or history of positive tuberculosis test; plus, presence of clinical symptoms, physical or radiographic findings).

-Any condition, including the presence of laboratory abnormalities and/or insufficient normal liver parenchyma, which places the subject at unacceptable risk if they were to participate in the study or confounds the ability to interpret data from the study.

Exclusion Criteria-Metastatic Colorectal Carcinoma

-Subjects with incontrovertible radiographic evidence of disease outside of the colon/rectum (primary) and liver given unlikelihood of benefit from liver-directed therapy.

Note: Lung lesions seen on CT do not always represent metastases. They are very hard to qualify, therefore exception to this exclusion is subjects with fewer than five lung lesions greater than 1 cm that have not increased in size by more than 10% over a 4-month period of time and are amenable to resection should subsequent problematic growth occur. Lesions less than 1 cm are indeterminant as far as etiology is concerned and will be ignored. Subjects with liver metastases and oligometastatic lung lesions (we define oligometastatic as less than 5 amenable to thoracoscopic removal) are still likely to benefit from liver directed therapy.

-Subjects who have undergone extra-hepatic metastasectomy and have a documented disease-free interval less than or equal to 4 months.

-MSI-high subjects who need to be treated with check-point inhibitors.

-Prior treatment with FUDR.

Exclusion Criteria-Intrahepatic Cholangiocarcinoma

-Presence of distant metastatic disease. Clinical or radiographic evidence of metastatic disease to regional lymph nodes will be allowed, provided it is amenable to resection.

-Prior treatment with FUDR.

-Diagnosis of sclerosing cholangitis.

-Clinical evidence or portal hypertension (ascites, gastroesophageal varices, or portal vein thrombosis).


--Back to Top--

Citations:

Not Provided

--Back to Top--

Contacts:

Principal Investigator

Referral Contact

For more information:

Jonathan M. Hernandez, M.D.
National Cancer Institute (NCI)
NIHBC 10 - CRC BG RM 4-3740
10 CENTER DR
BETHESDA MD 20892
(240) 760-6072
jonathan.hernandez@nih.gov

Cathleen E. Hannah, C.R.N.P.
National Cancer Institute (NCI)
NIHBC 10 - CRC BG RM 4-5740
10 CENTER DR
BETHESDA MD 20892
(240) 858-7006
cathleen.hannah@nih.gov

NCI Referral Office
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Bethesda, Maryland 20892, United States: NCI Clinical Trials Referral Office
1-888-NCI-1937

Clinical Trials Number:

NCT05286814

--Back to Top--

NIH Clinical Center Search the Studies: Study Number, Study Title

Protocol Details

Phase II Study Evaluating the Efficacy of M9241 in Combination with Hepatic Artery Infusion Pump (HAIP) and Systemic Therapy for Subjects with Metastatic Colorectal Cancer or Intrahepatic Cholangiocarcinoma

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

000307-C

Sponsoring Institute

National Cancer Institute (NCI)

Recruitment Detail

Type: Participants currently recruited/enrolled
Gender: Male & Female
Min Age: 18 Years
Max Age: N/A

Referral Letter Required

No

Population Exclusion(s)

Fetuses;
Pregnant Women;
Children

Keywords

Mcrc;
Icc;
NHS-IL12;
Response Rates;
Progression Free Survival (Pfs);
Overall Survival (Os);
Patient Survival;
Unresectable Liver Tumor;
SMART System

Recruitment Keyword(s)

None

Condition(s)

Metastatic Colorectal Cancer (Mcrc);
Intrahepatic Cholangiocarcinoma (Icc);
Colorectal Cancer;
Colorectal Neoplasms;
Cholangiocarcinoma;
Intrahepatic Bile Duct Cancer;
Bile Duct Cancer;
Bile Duct Neoplasms

Investigational Drug(s)

Floxuridine (FUDR)
5-Fluorouracil (5-FU)

Investigational Device(s)

None

Intervention(s)

Drug: Floxuridine
Drug: 5-Fluorouracil
Drug: Irinotecan
Device: Intera 3000 Hepatic Artery Infusion Pump (HAIP)
Drug: Oxaliplatin
Drug: Leucovorin
Drug: M9241
Drug: Gemcitabine
Drug: Dexamethasone

Supporting Site

National Cancer Institute

Background:

One way to treat liver cancer is to deliver chemotherapy drugs only to the liver (and not to the whole body). Researchers want to see if adding the drug M9241 can improve the treatment. The drug triggers the immune system to fight cancer.<TAB>

Objective:

To see if treatment with HAIPs to deliver liver-directed chemotherapy in combination with M9241 is effective for certain cancers.

Eligibility:

People aged 18 and older who have cancer of the bile ducts that is only in the liver, or colorectal cancer that has spread to the liver.

Design:

Participants will be screened with:

Medical history

Physical exam

Blood tests

Pregnancy test (if needed)

Tumor biopsy (if needed)

Electrocardiogram

Computed tomography (CT) scans

Participants will have an abdominal operation. A catheter will be placed into an artery that feeds blood to the liver. The catheter will then be attached to the HAIP. The HAIP will lay under the skin on the left side of the abdomen.

Participants will have chemotherapy drugs or heparin with saline infused into the HAIP every 2 weeks. M9241 will be injected under the skin every 4 weeks. They will get systemic chemotherapy through an IV or mediport every 2 weeks. They will receive this treatment until their cancer gets worse or they have bad side effects.

Participants will have 2 study visits each month. They will have CT scans every 8 weeks. At visits, they will repeat some screening tests.

Participants will have a follow-up visit 1 month after treatment ends. Then they will be contacted every 6 months for 5 years.

--Back to Top--

Eligibility

INCLUSION CRITERIA:

Inclusion Criteria- All Cohorts

-Age >= 18 years.

-Negative serum or urine pregnancy test at screening for women of childbearing potential (WOCBP).

NOTE: WOCBP is defined as any female who has experienced menarche and who has not undergone successful surgical sterilization or who is not postmenopausal. WOCBP must have a negative pregnancy test (HCG blood or urine) during screening

-Women of child-bearing potential and men must agree to use highly effective contraception prior to study entry, for the duration of study participation and for 3 months after completion of study treatment. Highly effective birth control (failure rate of less than 1%), e.g., intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, vasectomized partner and sexual abstinence. The use of condoms by male subjects is required unless the female partner is permanently sterile.

-Breastfeeding subject must agree to discontinue breastfeeding.

-Arterial anatomy on CT angiogram or CT chest, abdomen and pelvis multiphase (i.e., CT C/A/P multiphase) amenable to placement of the HAIP.

-Subject must sign the informed consent form to participate in this study.

-HIV-positive subjects may be considered for this study only if they have an undetectable viral load.

-Subjects must agree to co-enroll on the Surgical Oncology Program s tissue collection protocol 13C0176, Tumor, Normal Tissue and Specimens from Patients Undergoing Evaluation or Surgical Resection of Solid Tumors

-Subject s liver metastases must not be amenable to resection/ablation to No Evidence of Disease (NED) in one stage.

-Subject must be able to tolerate systemic chemotherapy at initiation of study treatment as outlined below (mCRC: FOLFOX or FOLFIRI; ICC: GemOx or FOLFOX).

Inclusion Criteria-Metastatic Colorectal Carcinoma

-Subjects must have histologically or cytologically confirmed diagnosis of colorectal adenocarcinoma metastatic to the liver (Cohort 1)

-Subjects must have measurable liver metastatic disease

-Subjects must have received 1st line systemic chemotherapy

-ECOG performance status <= 1

-Subjects must have adequate organ and marrow function as defined below:

--leukocytes > 3,000/mcL

--absolute neutrophil count > 1,500/mcL

--platelets > 90,000/mcL

--hemoglobin > 8 g/dL

--total bilirubin < 1.5 X institutional upper limit of normal

--AST(SGOT)/ALT(SGPT) < 2.5 X institutional upper limit of normal

--creatinine within normal institutional limits OR eGFR within normal as predicted by the CKD-EPI equation > 60 mL/min/1.73 m2..

Inclusion Criteria-Intrahepatic Cholangiocarcinoma

-Subjects must have histologically or cytologically confirmed diagnosis of intrahepatic cholangiocarcinoma confined to the liver (Cohort 2). Archival tumor sample may be used but if archival tissue is not available or is not adequate, tissue biopsy will be required.

-Clinical or radiographic evidence of metastatic disease to regional (porta hepatis) lymph nodes will be allowed, provided it is amenable to resection.

-Subjects must have radiographically measurable disease

-Disease must be considered unresectable at the time of preoperative evaluation.

-Subjects must have received 1st line systemic chemotherapy

-ECOG performance status <= 1.

-Subjects must have adequate organ and marrow function as defined below:

--leukocytes >= 2,000/ mm(3)

--absolute neutrophil count > 1,500/mcL

--platelets >= 75,000/ mm(3)

--hemoglobin > 8 g/dL

--total bilirubin < 1.5 mg/dl

--creatinine <= 1.5 mg/dl

EXCLUSION CRITERIA:

Exclusion Criteria- All Cohorts

-Subjects who are receiving any other investigational agents.

-Subjects who have previously received rIL-12

-Subjects with active autoimmune diseases, that might deteriorate when receiving an immunostimulatory agent with the exceptions:

-diabetes type I, vitiligo, alopecia, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible;

-subjects requiring hormone replacement with corticosteroids are eligible if the steroids are administered only for the purpose of hormonal replacement and at doses <= 10 mg of prednisone or equivalent per day;

-administration of steroids for other conditions through a route known to result in a minimal systemic exposure (topical, intranasal, intro-ocular, or inhalation) is eligible.

-History of organ transplant, except for transplants that do not require immunosuppression.

-History of or active inflammatory bowel disease (e.g., Crohn s disease, ulcerative colitis).

-Known hypersensitivity or allergic reactions attributed to any compounds of similar chemical or biologic composition to the study medication, such as recombinant IL-12 or other monoclonal antibodies and history of allergic reactions attributed to compounds of similar chemical composition to FUDR or heparin.

-Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke < 6 months prior to enrollment, myocardial infarction < 6 months prior to enrollment, unstable angina, congestive heart failure (>= NYHA III) or serious cardiac arrhythmia requiring medication.

-All conditions associated with significant necrosis of nontumor-bearing tissues.

-Esophageal or gastroduodenal ulcers < 6 months prior to treatment.

-Active ischemic bowel disease.

-Psychiatric illness/social situations that would limit compliance with study requirements.

-Active concurrent malignancies within the last five years other than colorectal primary except basal cell skin carcinoma and thyroid carcinoma.

-Prior radiation to liver.

-Subjects with active Hepatitis B or C infection.

-Significant acute or chronic infections (i.e., tuberculosis) history of exposure or history of positive tuberculosis test; plus, presence of clinical symptoms, physical or radiographic findings).

-Any condition, including the presence of laboratory abnormalities and/or insufficient normal liver parenchyma, which places the subject at unacceptable risk if they were to participate in the study or confounds the ability to interpret data from the study.

Exclusion Criteria-Metastatic Colorectal Carcinoma

-Subjects with incontrovertible radiographic evidence of disease outside of the colon/rectum (primary) and liver given unlikelihood of benefit from liver-directed therapy.

Note: Lung lesions seen on CT do not always represent metastases. They are very hard to qualify, therefore exception to this exclusion is subjects with fewer than five lung lesions greater than 1 cm that have not increased in size by more than 10% over a 4-month period of time and are amenable to resection should subsequent problematic growth occur. Lesions less than 1 cm are indeterminant as far as etiology is concerned and will be ignored. Subjects with liver metastases and oligometastatic lung lesions (we define oligometastatic as less than 5 amenable to thoracoscopic removal) are still likely to benefit from liver directed therapy.

-Subjects who have undergone extra-hepatic metastasectomy and have a documented disease-free interval less than or equal to 4 months.

-MSI-high subjects who need to be treated with check-point inhibitors.

-Prior treatment with FUDR.

Exclusion Criteria-Intrahepatic Cholangiocarcinoma

-Presence of distant metastatic disease. Clinical or radiographic evidence of metastatic disease to regional lymph nodes will be allowed, provided it is amenable to resection.

-Prior treatment with FUDR.

-Diagnosis of sclerosing cholangitis.

-Clinical evidence or portal hypertension (ascites, gastroesophageal varices, or portal vein thrombosis).


--Back to Top--

Citations:

Not Provided

--Back to Top--

Contacts:

Principal Investigator

Referral Contact

For more information:

Jonathan M. Hernandez, M.D.
National Cancer Institute (NCI)
NIHBC 10 - CRC BG RM 4-3740
10 CENTER DR
BETHESDA MD 20892
(240) 760-6072
jonathan.hernandez@nih.gov

Cathleen E. Hannah, C.R.N.P.
National Cancer Institute (NCI)
NIHBC 10 - CRC BG RM 4-5740
10 CENTER DR
BETHESDA MD 20892
(240) 858-7006
cathleen.hannah@nih.gov

NCI Referral Office
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Bethesda, Maryland 20892, United States: NCI Clinical Trials Referral Office
1-888-NCI-1937

Clinical Trials Number:

NCT05286814

--Back to Top--