NCT01347645

Irinotecan Plus E7820 Versus FOLFIRI in Second-Line Therapy in Patients With Locally Advanced or Metastatic Colon or Rectal Cancer

Terminated Phase 1, PHASE2 Results posted Last updated 22 June 2023

What this trial tests

Phase 1, PHASE2 trial testing FOLFIRI in Colon Cancer in 82 participants. Terminated before completion.

Timeline

30 September 2011

Primary endpoint
22 June 2015

22 June 2015

Quick facts

Lead sponsor	Eisai Inc.
Phase	Phase 1, PHASE2
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	82
Start date	30 September 2011
Primary completion	22 June 2015
Estimated completion	22 June 2015
Sites	38 locations across Russia, Ukraine, Argentina, Australia, United States, Brazil

Drugs / interventions tested

• FOLFIRI (folfiri) — full drug profile →
• E7820 — full drug profile →

Conditions studied

• Colon Cancer — all drugs for Colon Cancer →
• Rectal Cancer — all drugs for Rectal Cancer →

Sponsor

Eisai Inc. — full company profile →

Who can join

18 and older, any sex, with Colon Cancer or Rectal Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Phase 1b: Maximum Tolerated Dose (MTD) of E7820 With Irinotecan as Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0 Primary · Up to 12 cycles (each cycle length =14 days)

MTD: maximum dose that was determined to be safe and tolerable for Phase 2.If two dose limiting toxicities (DLTs) occurred at any dose level,MTD: preceding dose/intermediate dose.DLT was graded according to CTCAE v4.0. Includes \>= Grade 3(G3) peripheral neuropathy,\>=G3 nausea/vomiting despite optimal anti-emetic treatment, any other non-hematologic toxicity of \>=G3(except alopecia, single abnormal laboratory values Investigator judged unlikely related to study therapy, had no clinical correlate, resolved in 7 days, hypersensitivity reaction to any of compounds),Grade 4 neutropenia lasting o

Group	Value	95% CI
Phase 1b, All Participants	NA

Phase 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Primary · From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)

TEAE is defined as an adverse event that had an onset date, or a worsening in severity on or after the first dose of study drug up to the end of the study. Number of participants with TEAEs are reported based on safety assessments of laboratory tests, physical examination, examining bowel movements, regular measurement of vital signs, eastern cooperative oncology group-performance status and electrocardiogram parameter values. SAE is any untoward medical occurrence that at any dose: resulted in death; life threatening required inpatient hospitalization; resulted in persistent, significant disa

TEAEs

Group	Value	95% CI
Phase 2: E7820 70 mg + Irinotecan	34
Phase 2: Folfiri	34

SAEs

Group	Value	95% CI
Phase 2: E7820 70 mg + Irinotecan	10
Phase 2: Folfiri	8

Phase 2: Progression Free Survival (PFS) Secondary · From date of randomization up to 1 year and 2 months

PFS is defined as the time from the date of randomization of a participant until the sooner of (1) the date of first documented progression of such participant's disease (PD) based on Investigator assessments according to response evaluation criteria in solid tumor (RECIST) version (v) 1.1. or; (2) the date of such participant's death due to any cause. PD is defined as at least a 20 percent (%) increase or 5 millimeter (mm) increase in the sum of diameters of target lesions (taking as reference the smallest sum on study) recorded since the treatment started or the appearance of 1 or more new l

Group	Value	95% CI
Phase 2: E7820 70 mg + Irinotecan	17.1	9.00 – 32.29
Phase 2: Folfiri	33.7	24.14 – 45.43

Phase 2: Overall Survival (OS) Secondary · From date of randomization up to 1 year and 2 months

OS is defined as time from the date of randomization of a participant until the date of death of such participant, regardless of the actual cause of the participant's death.

Group	Value	95% CI
Phase 2: E7820 70 mg + Irinotecan	NA	NA – NA
Phase 2: Folfiri	NA	NA – NA

Phase 2: Time to Progression (TTP) Secondary · From date of randomization up to 1 year and 2 months

TTP is defined as time from the date of randomization of a participant until the date of first documented progression of such participant's disease. PD is defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking in reference the smallest summed longest diameters on study (this included the baseline sum if that was the smallest on study). In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. The appearance of 1 or more new lesions was also considered progression.

Group	Value	95% CI
Phase 2: E7820 70 mg + Irinotecan	23.7	14.43 – 33.00
Phase 2: Folfiri	33.7	24.14 – 45.43

Phase 2: Percentage of Participants With Overall Response Secondary · From date of randomization up to 1 year and 2 months

ORR is defined as percentage of participants in the study whose best overall response is either complete response (CR) or partial response (PR) based on RECIST v1.1. CR is defined as complete disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to less than 10 mm. PR is defined as at least a 30% decrease in the sum of the longest diameters of target lesions, taking as reference the baseline summed longest diameters.

Group	Value	95% CI
Phase 2: E7820 70 mg + Irinotecan	20.6	8.7 – 37.9
Phase 2: Folfiri	20.6	8.7 – 37.9

Adverse events — posted to ClinicalTrials.gov

Time frame: From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Phase 1b: Cohort 1: E7820 40 mg + Irinotecan

Serious: 2/3 (67%)

Deaths: 1/3

Phase 1b: Cohort 2: E7820 70 mg + Irinotecan

Serious: 1/8 (13%)

Deaths: 5/8

Phase 1b: Cohort 3: E7820 100 mg + Irinotecan

Serious: 0/3 (0%)

Deaths: 2/3

Phase 2: E7820 70 mg + Irinotecan

Serious: 10/34 (29%)

Deaths: 7/34

Phase 2: Folfiri

Serious: 8/34 (24%)

Deaths: 7/34

Serious adverse events (22 terms)

Reaction	System	Phase 1b: Cohort 1: E7820 …	Phase 1b: Cohort 2: E7820 …	Phase 1b: Cohort 3: E7820 …	Phase 2: E7820 70 mg + Iri…	Phase 2: Folfiri
Neutropenia	Blood and lymphatic system disorders	—	—	—	—	—
Cardiovascular insufficiency	Cardiac disorders	—	—	—	—	—
Febrile neutropenia	Blood and lymphatic system disorders	—	—	—	—	—
Colitis	Gastrointestinal disorders	—	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—	—
Gastroenteritis	Infections and infestations	—	—	—	—	—
Rhabdomyolysis	Musculoskeletal and connective tissue disorders	—	—	—	—	—
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—	—	—
Intestinal obstruction	Gastrointestinal disorders	—	—	—	—	—
Pyrexia	General disorders	—	—	—	—	—
Thrombosis in device	General disorders	—	—	—	—	—
Clostridium difficile colitis	Infections and infestations	—	—	—	—	—
Device related infection	Infections and infestations	—	—	—	—	—
Lobar pneumonia	Infections and infestations	—	—	—	—	—
Lung infection	Infections and infestations	—	—	—	—	—
Alanine aminotransferase increased	Investigations	—	—	—	—	—
Loss of consciousness	Nervous system disorders	—	—	—	—	—
Acute kidney injury	Renal and urinary disorders	—	—	—	—	—
Haematuria	Renal and urinary disorders	—	—	—	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—

Other adverse events (105 terms — click to expand)

Reaction	System	Phase 1b: Cohort 1: E7820 …	Phase 1b: Cohort 2: E7820 …	Phase 1b: Cohort 3: E7820 …	Phase 2: E7820 70 mg + Iri…	Phase 2: Folfiri
Neutropenia	Blood and lymphatic system disorders	—	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—	—
Alopecia	Skin and subcutaneous tissue disorders	—	—	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—	—	—
Leukopenia	Blood and lymphatic system disorders	—	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—	—
Asthenia	General disorders	—	—	—	—	—
Fatigue	General disorders	—	—	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—	—	—
Pyrexia	General disorders	—	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—	—
Stomatitis	Gastrointestinal disorders	—	—	—	—	—
Alanine aminotransferase increased	Investigations	—	—	—	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—	—	—	—
Lymphopenia	Blood and lymphatic system disorders	—	—	—	—	—
Respiratory tract infection	Infections and infestations	—	—	—	—	—
Hyperkalaemia	Metabolism and nutrition disorders	—	—	—	—	—
Aspartate aminotransferase increased	Investigations	—	—	—	—	—
Blood alkaline phosphatase increased	Investigations	—	—	—	—	—
Dizziness	Nervous system disorders	—	—	—	—	—
Headache	Nervous system disorders	—	—	—	—	—
Insomnia	Psychiatric disorders	—	—	—	—	—
Respiratory tract infection viral	Infections and infestations	—	—	—	—	—
Creatinine renal clearance decreased	Investigations	—	—	—	—	—
Thrombocytopenia	Blood and lymphatic system disorders	—	—	—	—	—
Mucosal inflammation	General disorders	—	—	—	—	—
Urinary tract infection	Infections and infestations	—	—	—	—	—
Neutrophil count decreased	Investigations	—	—	—	—	—
Weight decreased	Investigations	—	—	—	—	—
White blood cell count decreased	Investigations	—	—	—	—	—
Hyperglycaemia	Metabolism and nutrition disorders	—	—	—	—	—
Hypocalcaemia	Metabolism and nutrition disorders	—	—	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—	—	—
Neuropathy peripheral	Nervous system disorders	—	—	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—
Hyperhidrosis	Skin and subcutaneous tissue disorders	—	—	—	—	—
Rash	Skin and subcutaneous tissue disorders	—	—	—	—	—
Dyspepsia	Gastrointestinal disorders	—	—	—	—	—
Oedema peripheral	General disorders	—	—	—	—	—

Most-reported serious reactions: Neutropenia, Cardiovascular insufficiency, Febrile neutropenia, Colitis, Diarrhoea, Gastroenteritis, Rhabdomyolysis, Pulmonary oedema.

Data from ClinicalTrials.gov NCT01347645 adverse events section.

Sponsor's own description

The purpose of the Phase Ib portion is to find out the highest dose of study drug that can safely be given when tested in a small group of subjects.

The purpose of the Phase II portion is to find out how safe the study drug is when taken at the highest dose in a larger group of subjects.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Targeting integrin pathways: mechanisms and advances in therapy.
   Pang X, He X, Qiu Z, Zhang H, et al · · 2023 · cited 704× · PMID 36588107 · DOI 10.1038/s41392-022-01259-6
2. The force awakens: metastatic dormant cancer cells.
   Park SY, Park SY, Nam JS. · · 2020 · cited 149× · PMID 32300189 · DOI 10.1038/s12276-020-0423-z
3. Beyond matrix stiffness: targeting force-induced cancer drug resistance.
   Kalli M, Poskus MD, Stylianopoulos T, Zervantonakis IK. · · 2023 · cited 112× · PMID 37558577 · DOI 10.1016/j.trecan.2023.07.006
4. RNA-binding protein 39: a promising therapeutic target for cancer.
   Xu C, Chen X, Zhang X, Zhao D, et al · · 2021 · cited 57× · PMID 34389703 · DOI 10.1038/s41420-021-00598-7
5. Prognostic Significance of Integrin Subunit Alpha 2 (ITGA2) and Role of Mechanical Cues in Resistance to Gemcitabine in Pancreatic Ductal Adenocarcinoma (PDAC).
   Gregori A, Bergonzini C, Capula M, Mantini G, et al · · 2023 · cited 26× · PMID 36765586 · DOI 10.3390/cancers15030628
6. Tissue mechanics in tumor heterogeneity and aggression.
   Finger AM, Hendley AM, Figueroa D, Gonzalez H, et al · · 2025 · cited 18× · PMID 40307158 · DOI 10.1016/j.trecan.2025.04.004
7. Integrin α2β1 Represents a Prognostic and Predictive Biomarker in Primary Ovarian Cancer.
   Dötzer K, Schlüter F, Koch FEV, Brambs CE, et al · · 2021 · cited 10× · PMID 33809043 · DOI 10.3390/biomedicines9030289
8. Molecular glue degrader for tumor treatment.
   Hu Y, Yan Y, Wang J, Hou J, et al · · 2024 · cited 8× · PMID 39759140 · DOI 10.3389/fonc.2024.1512666