Neoplasms

All Conditions

Digestive System Diseases

Rare Diseases

Adenocarcinoma

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Small Intestinal Adenocarcinoma

Anti-Infective Agents

All Drugs and Chemicals

Antineoplastic Agents

Metronidazole

Pembrolizumab

Vancomycin

Nivolumab

Neomycin

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Anti-Bacterial Agents

Antiprotozoal Agents

Antiparasitic Agents

Enzyme Inhibitors

Patients receive metronidazole PO Q8H on days -14 to -8 and then vancomycin PO Q6H and neomycin PO Q6H on days -8 to -6. Patients then undergo colonoscopic FMT on day -5.

POST-COLONOSCOPIC FMT: Patients receive standard of care pembrolizumab IV over 30 minutes on day 1. Patients also receive fecal microbiota transplantation capsule PO on days 1, 8, and 15 of cycle 1. Beginning in cycle 2, patients receive fecal microbiota transplantation capsule PO on day 1. Cycles repeat every 21 days for up to 6 months in the absence of disease progression or unacceptable toxicity.

Patients receive metronidazole PO Q8H on days -14 to -8 and then vancomycin PO Q6H and neomycin PO Q6H on days -8 to -6. Patients then undergo colonoscopic FMT on day -5.

POST-COLONOSCOPIC FMT: Patients receive standard of care nivolumab IV over 30 minutes on day 1. Patients also receive fecal microbiota transplantation capsule PO on days 1 and 8 of cycles 1-2. Beginning in cycle 4, patients receive fecal microbiota transplantation capsule PO on day 1 of every other cycle. Cycles repeat every 14 days for up to 6 months in the absence of disease progression or unacceptable toxicity.

Biopsy

Fecal Microbiota Transplantation

Fecal Microbiota Transplantation Capsule

Questionnaire Administration

Michael J Overman

This phase II trial studies the effect of fecal microbiota transplant and re-introduction of anti-PD-1 therapy (pembrolizumab or nivolumab) in treating anti-PD-1 non-responders with colorectal cancer that has spread to other places in the body (metastatic). Fecal microbiota transplants contain the normal bacteria and viruses found in fecal (stool) material. Immunotherapy with monoclonal antibodies, such as pembrolizumab and nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving pembrolizumab or nivolumab with fecal microbiota transplants may help to control the disease.

PRIMARY OBJECTIVE:

I. To evaluate the efficacy of pembrolizumab or nivolumab in conjunction with fecal microbiota transplant (FMT) from PD-1 responding mismatch-repair deficiency (dMMR) colorectal cancer (CRC) patients for treatment of PD-1 non-responding dMMR CRC patient.

Fecal Microbiota Transplant and Re-introduction of Anti-PD-1 Therapy (Pembrolizumab or Nivolumab) for the Treatment of Metastatic Colorectal Cancer in Anti-PD-1 Non-responders

Pilot Trial of Fecal Microbiota Transplantation and Re-Introduction of Anti-PD-1 Therapy in dMMR Colorectal Adenocarcinoma Anti-PD-1 Non-Responders

Assessed by Immune-Modified Response Evaluation Criteria in Solid Tumors (iRECIST). Will be summarized by mean, standard error, and 95% confidence interval.

National Cancer Institute (NCI)

M.D. Anderson Cancer Center

Symptoms and General Pathology

Carcinoma, Squamous Cell

Syndrome

Neoplasms, Squamous Cell

Adenocarcinoma of the Appendix

Atezolizumab

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Immunologic Factors

Participants receive cobimetinib PO QD on days 1-21 and atezolizumab IV over 60 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cobimetinib

Kanwal P Raghav

This phase II trial studies how well cobimetinib and atezolizumab work in treating participants with rare tumors that have spread to other places in the body (advanced) or that does not respond to treatment (refractory). Cobimetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving cobimetinib and atezolizumab may work better in treating participants with advanced or refractory rare tumors.

PRIMARY OBJECTIVE:

I. To evaluate the efficacy of cobimetinib plus atezolizumab (COTEZO) in cohorts of advanced rare tumors using objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1.

SECONDARY OBJECTIVES:

I. To determine progression-free survival (PFS) on COTEZO in cohorts of advanced rare tumors per RECIST v1.1 and immune-related (ir)RECIST.

II. To determine overall survival (OS) on COTEZO in cohorts of advanced rare tumors.

III. To determine disease control rate (DCR) and duration of response (DOR) on COTEZO in cohorts of advanced rare tumors per RECIST v1.1 and irRECIST.

IV. To determine objective response rate (ORR) per immune-related RECIST criteria.

V. To determine safety profile and adverse events encountered by patients with advanced rare tumors treated with COTEZO.

VI. To collect and bank tumor tissue and peripheral blood for future correlative analyses from patients with advanced rare tumors treated with COTEZO.

OUTLINE:

Participants receive cobimetinib orally (PO) once daily (QD) on days 1-21 and atezolizumab intravenously (IV) over 60 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, participants followed up every 3 months thereafter.

Cobimetinib and Atezolizumab in Treating Participants With Advanced or Refractory Rare Tumors

A Phase II, Open-Label, Single-Arm, Multi-Cohort, Proof-of-Principle Study to Investigate the Efficacy of Cobimetinib and Atezolizumab in Advanced Rare Tumors

ORR (partial response (PR) or complete response (CR) measured as per RECIST 1.1.

Small Intestine Cancer

Micronutrients

Hematinics

Bone Density Conservation Agents

Vitamins

Irinotecan

Paclitaxel

Leucovorin

Fluorouracil

Levoleucovorin

Albumin-Bound Paclitaxel

Calcium

Folic Acid

Camptothecin

Calcium, Dietary

Ramucirumab

Lexatumumab

Vitamin B Complex

Immunoglobulins, Intravenous

Tubulin Modulators

Antimitotic Agents

Hormones

Antimetabolites

Immunosuppressive Agents

Topoisomerase I Inhibitors

Antidotes

Protective Agents

Trace Elements

Angiogenesis Inhibitors

Growth Inhibitors

Folinic Acid

Folate

Vitamin B9

Patients receive ramucirumab IV over 30-60 minutes on days 1 and 15, and paclitaxel IV over 30 minutes on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients receive irinotecan IV over 90 minutes on days 1 and 15, leucovorin IV over 2 hours on days 1 and 15, and fluorouracil IV bolus on days 1 and 15. Patients also receive fluorouracil IV over 46-48 hours on days 1-3 and 15-17. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Irinotecan Hydrochloride

Leucovorin Calcium

Christy Klepetko

Dana Sparks

Site Public Contact

Charles W. Drescher

John A. Ellerton

Jay W. Carlson

Gary L. Buchschacher

Christopher M. Reynolds

John M. Schallenkamp

Kendrith M. Rowland

Bryan A. Faller

Ardaman Shergill

This phase II trial studies how well ramucirumab and paclitaxel or the FOLFIRI regimen (leucovorin calcium, fluorouracil, and irinotecan hydrochloride) work in treating patients with small bowel cancers that have spread extensively to other anatomic sites (advanced) or are no longer responding to treatment (refractory). Ramucirumab is a monoclonal antibody that attaches to and inhibits a molecule called VEGFR-2. This may restrain new blood vessel formation therefore reducing nutrient supply to tumor which may interfere with tumor cell growth and expansion. Drugs used in chemotherapy, such as paclitaxel, leucovorin calcium, fluorouracil, and irinotecan 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 Ramucirumab plus paclitaxel or FOLFIRI, may be helpful in treating advanced or refractory small bowel cancers and may help patients live longer.

PRIMARY OBJECTIVES:

I. To evaluate whether progression-free survival (PFS) meets an efficacy threshold in patients with previously treated advanced small bowel adenocarcinoma who receive treatment with ramucirumab and paclitaxel or FOLFIRI.

II. If the stated threshold is met in both arms, to choose the better regimen with respect to progression free survival (PFS).

SECONDARY OBJECTIVES:

I. To assess overall response rate (ORR) \[complete and partial, confirmed and unconfirmed\] in the subset of patients with measurable disease treated with ramucirumab and paclitaxel or FOLFIRI in this patient population.

II. To assess overall survival (OS) in patients treated with ramucirumab and paclitaxel or FOLFIRI in this patient population.

III. To evaluate safety and toxicity associated with combination ramucirumab and paclitaxel treatment or FOLFIRI therapy in this patient population.

TRANSLATIONAL OBJECTIVES:

I. To explore the correlation of maximum decrease in CEA levels and time to maximum decrease in CEA levels with PFS, OS, and ORR.

II. To bank tissue and blood samples for other future correlative studies from patients enrolled on the study.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive ramucirumab intravenously (IV) over 30-60 minutes on days 1 and 15, and paclitaxel IV over 30 minutes on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive irinotecan IV over 90 minutes on days 1 and 15, leucovorin IV over 2 hours on days 1 and 15, and fluorouracil IV bolus on days 1 and 15. Patients also receive fluorouracil IV over 46-48 hours on days 1-3 and 15-17. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients completing study treatment are followed up every 8 weeks until disease progression. Once the disease has progressed, patients are followed up every 6 months for up to 3 years post registration.

Ramucirumab and Paclitaxel or FOLFIRI in Advanced Small Bowel Cancers

Randomized Phase II Selection Study of Ramucirumab and Paclitaxel Versus FOLFIRI in Refractory Small Bowel Adenocarcinoma

CEA levels will be measured at the beginning of the first cycle and every 8 weeks during the study. Maximum decrease in CEA levels from treatment onset and time to maximum decrease in CEA will be summarized in descriptive analyses. Decrease in CEA levels will be defined as high (\>= 50% change) versus low (\< 50% change).

PFS will be assessed in all eligible and evaluable (received at least one dose of protocol therapy) patients using the Kaplan-Meier method, with statistical differences in event rates between treatment arms assessed via stratified Cox regression model.

Probabilities of OS will be estimated using the method of Kaplan-Meier, with statistical differences in event rates between treatment arms assessed via stratified Cox regression model.

Will be assessed by Response Evaluation Criteria in Solid Tumors 1.1. Will be compared across treatment arms via chi-square tests.

Will be compared across treatment arms via chi-square tests.

SWOG Cancer Research Network

Recurrence

Patients receive pembrolizumab IV over 30 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Laboratory Biomarker Analysis

Robert McWilliams

This phase II trial studies how well pembrolizumab works in treating patients with small bowel adenocarcinoma that has spread to other places in the body or that cannot be removed by surgery. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread.

PRIMARY OBJECTIVES:

I. To determine whether pembrolizumab administered to small bowel adenocarcinoma (SBA) patients demonstrates antitumor activity as measured by the confirmed response rate.

SECONDARY OBJECTIVES:

I. To assess survival endpoints (overall survival \[OS\], progression free survival \[PFS\]), including stratified analysis by tumor site.

II. To assess whether pembrolizumab is safe in SBA patients by assessing adverse events.

TERTIARY OBJECTIVES:

I. To determine whether PD-L1 expression, as measured by immunohistochemistry (IHC), or microsatellite instability (MSI) status is associated with the response rate overall.

II. To determine if Bim levels in tumor-reactive CD11ahighPD-1+CD8+ peripheral blood T cells can objectively monitor responses to pembrolizumab and to determine if excessive release of soluble B7-H1 (soluble \[s\]PD-L1) by the tumor leads to Bim upregulation and treatment resistance in SBA.

III. To determine if other tissue-based factors, such as total mutational burden, correlate with response to pembrolizumab.

OUTLINE:

Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months until disease progression, and then every 6 months for up to 5 years.

Pembrolizumab in Treating Patients With Small Bowel Adenocarcinoma That is Metastatic or Locally Advanced and Cannot Be Removed by Surgery

A Multicenter Phase II Study of Pembrolizumab (MK-3475) in Patients With Advanced Small Bowel Adenocarcinomas

Correlated with clinical data (i.e. response, overall survival, progression free survival, adverse events). These correlations will be done using the Chi-square or Fisher?s exact test for categorical data and Kaplan-Meier methods (including the log-rank test) for the survival endpoints. Univariate Cox regression models will also be done to assess for marker effects on survival endpoints. Descriptive statistics and graphical methods will be used to summarize the data as well. All these analyses will be done overall and by MMR/microsatellite instability status.

The response rate (percentage) is the percent of patients whose best response was Complete Response (CR) or Partial Response (PR) as defined by RECIST 1.1 criteria. Percentage of successes will be estimated by 100 times the number of successes divided by the total number of evaluable patients.

Progression free survival (PFS) is defined as the time from the date of randomization to the date of disease progression or death resulting from any cause, whichever comes first. Progression is defined according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator.

Overall survival time is defined as the time from randomization to death due to any cause. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator.

number of participants who experienced at least one grade 3 or higher adverse events regardless of attribution assessed by National Cancer Institute's Common Terminology Criteria for Adverse Events version 4.03

Academic and Community Cancer Research United

Patients receive 200 mg pembrolizumab IV over 30 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Treatment (Pembrolizumab)

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

Eastern Cooperative Oncology Group PS Scale: 0)Fully active, able to carry on all pre-disease performance without restriction; 1)Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work; 2)Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours; 3)Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours; 4)Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair.

ECOG Performance Status

Robert R. McWilliams, M.D.

Overall Confirmed Response Rate

Progression Free Survival

Overall Survival

Number of Participants Who Experienced at Least One Grade 3 or Higher Adverse Events Regardless of Attribution

Biomarker Levels

Overall Study

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Fecal Microbiota Transplant and Re-introduction of Anti-PD-1 Therapy (Pembrolizumab or Nivolumab) for the Treatment of Metastatic Colorectal Cancer in Anti-PD-1 Non-responders	NCT04729322	Metastatic Colo... Metastatic Smal... Stage IV Colore... Stage IV Small ... Stage IVA Color... Stage IVB Color... Stage IVC Color...	Biopsy Fecal Microbiot... Fecal Microbiot... Metronidazole Neomycin Nivolumab Pembrolizumab Questionnaire A... Vancomycin	18 Years -	M.D. Anderson Cancer Center
Cobimetinib and Atezolizumab in Treating Participants With Advanced or Refractory Rare Tumors	NCT03108131	Skin Squamous C... Appendix Adenoc... Rare Lesion Locally Advance... Locally Advance... Metastatic Mali... Metastatic Skin... Metastatic Smal... Rare Neoplastic... Refractory Mali... Stage IV Small ... Unresectable Ma...	Atezolizumab Cobimetinib	18 Years -	M.D. Anderson Cancer Center
Fecal Microbiota Transplant and Re-introduction of Anti-PD-1 Therapy (Pembrolizumab or Nivolumab) for the Treatment of Metastatic Colorectal Cancer in Anti-PD-1 Non-responders	NCT04729322	Metastatic Colo... Metastatic Smal... Stage IV Colore... Stage IV Small ... Stage IVA Color... Stage IVB Color... Stage IVC Color...	Biopsy Fecal Microbiot... Fecal Microbiot... Metronidazole Neomycin Nivolumab Pembrolizumab Questionnaire A... Vancomycin	18 Years -	M.D. Anderson Cancer Center
Ramucirumab and Paclitaxel or FOLFIRI in Advanced Small Bowel Cancers	NCT04205968	Metastatic Smal... Stage III Small... Stage IIIA Smal... Stage IIIB Smal... Stage IV Small ...	Fluorouracil Irinotecan Irinotecan Hydr... Leucovorin Leucovorin Calc... Paclitaxel Ramucirumab	18 Years -	SWOG Cancer Research Network
Pembrolizumab in Treating Patients With Small Bowel Adenocarcinoma That is Metastatic or Locally Advanced and Cannot Be Removed by Surgery	NCT02949219	Metastatic Smal... Recurrent Small... Unresectable Sm...	Laboratory Biom... Pembrolizumab	18 Years -	Academic and Community Cancer Research United
Fecal Microbiota Transplant and Re-introduction of Anti-PD-1 Therapy (Pembrolizumab or Nivolumab) for the Treatment of Metastatic Colorectal Cancer in Anti-PD-1 Non-responders	NCT04729322	Metastatic Colo... Metastatic Smal... Stage IV Colore... Stage IV Small ... Stage IVA Color... Stage IVB Color... Stage IVC Color...	Biopsy Fecal Microbiot... Fecal Microbiot... Metronidazole Neomycin Nivolumab Pembrolizumab Questionnaire A... Vancomycin	18 Years -	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for metastatic small intestinal adenocarcinoma