Pilot Trial of CRLX101 in Treatment of Patients With Advanced or Metastatic Stomach, Gastroesophageal, or Esophageal Cancer That Cannot be Removed by Surgery

NCT01612546 | Completed Phase 2 Results DMC

• 2 other identifiers: 11276NCI-2012-00893
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This pilot clinical trial studies cyclodextrin-based nanopharmaceutical CRLX101 in treating patients with advanced or metastatic stomach, gastroesophageal, or esophageal cancer that has progressed through at least one prior regimen of chemotherapy and cannot be removed by surgery. CRLX101 delivers the cytotoxic topoisomerase-1 inhibitor camptothecin into tumor cells and is hypothesized to interrupt the growth of tumor cells.

Conditions

Adenocarcinoma of the Esophagus; Adenocarcinoma of the Gastroesophageal Junction; Diffuse Adenocarcinoma of the Stomach; Intestinal Adenocarcinoma of the Stomach; Mixed Adenocarcinoma of the Stomach; Recurrent Esophageal Cancer; Recurrent Gastric Cancer; Squamous Cell Carcinoma of the Esophagus; Stage IIIB Esophageal Cancer; Stage IIIB Gastric Cancer; Stage IIIC Esophageal Cancer; Stage IIIC Gastric Cancer; Stage IV Esophageal Cancer; Stage IV Gastric Cancer

Outcome Measures

Primary Outcomes (1)

• CRLX101 (CPT) Uptake in Tumor and Nearby Normal Tissue

  Using Fisher's Exact to determine statistical significance in detection of a CPT fluorescence signal posttreatment between tumor and adjacent normal tissue biopsy specimens.

  Baseline and day 8

Secondary Outcomes (4)

• Overall Objective Response Rate

  Up to 4 years

• Clinical Benefit Rate

  At least 4 months post treatment, assessed up to 4 years

• Overall Survival

  From date of start of therapy to date of death due to any cause, assessed up to 4 years

• Incidence of Adverse Events

  Up to 4 years

Study Arms (1)

Treatment (cyclodextrin-based polymer-camptothecin CRLX101)

EXPERIMENTAL

Patients receive cyclodextrin-based polymer-camptothecin CRLX101 IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. After the completion of 6 courses, patients achieving stable disease or better may receive treatment for an additional 6 months.

Drug: cyclodextrin-based polymer-camptothecin CRLX101; Other: Laboratory biomarker analysis; Other: Pharmacological studies

Interventions

cyclodextrin-based polymer-camptothecin CRLX101 DRUG

Given IV

Also known as: CRLX101, cyclodextrin-based polymer-camptothecin IT-101, IT-101

Treatment (cyclodextrin-based polymer-camptothecin CRLX101)

Laboratory biomarker analysis OTHER

Correlative studies

Treatment (cyclodextrin-based polymer-camptothecin CRLX101)

Pharmacological studies OTHER

Correlative studies

Treatment (cyclodextrin-based polymer-camptothecin CRLX101)

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically confirmed advanced or metastatic squamous adenocarcinoma of the esophagus, GEJ, or stomach
• Patients must have primary tumor and adjacent normal tissue accessible via endoscopic biopsy
• Patients must have received at least one prior chemotherapy regimen for their unresectable or metastatic disease, not including treatment administered in the adjuvant and/or neoadjuvant setting for curative intent
• Patients must have measurable or evaluable disease
• Absolute neutrophil count \>= 1500 cells/uL
• Platelets \>= 100,000 cells/uL
• Total bilirubin =\< 1.5 times the upper limit of normal (ULN)
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =\< 2.5 x ULN
• AST/ALT =\< 5 x ULN if liver metastasis is present
• Serum creatinine =\< 1.5 mg/dL or a measured creatinine clearance \>= 50 mL/min
• Prothrombin time (PT)/partial thromboplastin time (PTT) =\< 1.5 x ULN
• Subjects with an Eastern Cooperative Oncology Group (ECOG) performance status of =\< 2
• Subjects with a life expectancy \>= 12 weeks
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for six months following duration of study participation; should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately and be discontinued on study; subjects should be instructed to notify the investigator if it is determined after completion of the study that they became pregnant during the treatment phase of the study; the anticipated date or birth or termination of the pregnancy should be provided at the time of the initial report; whenever possible, a pregnancy should be followed to term, any premature terminations reported, and the status of the mother and the child should be reported to the study monitor after delivery; if the outcome of the pregnancy meets any severe adverse events (SAE) classification criterion, the investigator must follow the procedures for reporting SAEs; any neonatal death occurring =\< 30 days after birth must also be reported as a SAE
• Subjects must have an electrocardiogram without evidence of clinically significant conduction abnormalities or active ischemia as determined by the investigator and an acceptable QTc interval

You may not qualify if:

• Female subjects who are pregnant or nursing
• Subjects who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to first dose of study drug or those who have not had adverse events return to baseline severity level or a severity of grade 1 due to agents administered more than 4 weeks prior to first dose of study drug
• Subjects with a history of congestive heart failure (CHF) requiring medical therapy
• Subjects with serum amylase or lipase \> 1.5 ULN
• Subjects with previous high dose chemotherapy with autologous stem cell rescue bone marrow transplantation
• History of organ or allogeneic bone marrow transplant
• Use of any investigational agent or device within 4 weeks prior to first dose of study drug
• Metastatic disease to the central nervous system (CNS) requiring treatment or radiation therapy
• Subjects with known untreated brain metastases or treated brain metastases that have not been stable \>= 4 weeks prior to first dose of study drug
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection (including human immunodeficiency virus \[HIV\] not stable on antiretroviral therapy), symptomatic congestive heart failure, hypertension, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements, as determined by the investigator
• History of prior malignancy not cured by excision; patients with non-melanoma skin cancer or carcinoma in situ of the cervix are not excluded, but patients with other prior malignancies must have had at least 2-year disease free interval
• Concurrent therapeutic anticoagulation: PTT less than or equal to 1.5 x ULN or low dose aspirin and low-molecular weight heparin only are allowed; Coumadin will be allowed on a case by case basis if use is chronic and approved by the study medical monitors
• Any major surgery =\< 4 week prior to first dose of study drug
• Concurrent use of filgrastim (G-CSF) or growth factors at the time of initiation of study drug
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to CRLX101 and camptothecins

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

MeSH Terms

Conditions

Adenocarcinoma Of Esophagus; Esophageal Neoplasms; Stomach Neoplasms; Esophageal Squamous Cell Carcinoma

Interventions

IT-101

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Stomach Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Squamous Cell

Results Point of Contact

• Title: Paul Frankel, Ph.D.
• Organization: City of Hope

pfrankel@coh.org

626-218-5265

Study Officials

• Joseph Chao

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 4, 2012
• First Posted: June 6, 2012
• Study Start: November 1, 2012
• Primary Completion: January 15, 2015
• Study Completion: January 15, 2015
• Last Updated: February 1, 2018
• Results First Posted: December 27, 2017

Record last verified: 2018-01

Locations

US (1)