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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by City of Hope Medical Center
Sponsor:
Collaborator:
Information provided by (Responsible Party):
City of Hope Medical Center
ClinicalTrials.gov Identifier:
NCT01612546
First received: June 4, 2012
Last updated: August 1, 2014
Last verified: August 2014
  Purpose

This pilot clinical trial studies cyclodextrin-based nanopharmaceutical CRLX101 in treating patients with advanced or metastatic HER-2 negative 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.


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

Study Type: Interventional
Study Design: Endpoint Classification: Bio-availability Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pilot Trial of CRLX101 in the Treatment of Patients With Advanced HER-2 Negative Gastric, Gastroesophageal, or Esophageal Squamous or Adenocarcinoma

Resource links provided by NLM:


Further study details as provided by City of Hope Medical Center:

Primary Outcome Measures:
  • Change in CRLX101 uptake in tumor and nearby normal tissue [ Time Frame: Baseline and day 8 ] [ Designated as safety issue: No ]
    The effect size is the mean difference divided by the standard deviation of the difference.


Secondary Outcome Measures:
  • Response (Complete Response + Partial Response) assessed using Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
  • Clinical benefit (Complete Response + Partial Response + Stable Disease) [ Time Frame: At least 4 months post treatment, assessed up to 4 years ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: From date of start of therapy to date of death due to any cause, assessed up to 4 years ] [ Designated as safety issue: No ]
  • Incidence of adverse events [ Time Frame: Up to 4 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 11
Study Start Date: November 2012
Estimated Primary Completion Date: July 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (cyclodextrin-based polymer-camptothecin CRLX101)
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.
Drug: cyclodextrin-based polymer-camptothecin CRLX101
Given IV
Other Names:
  • CRLX101
  • cyclodextrin-based polymer-camptothecin IT-101
  • IT-101
Other: Laboratory biomarker analysis
Correlative studies
Other: Pharmacological studies
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To evaluate pre- and post-treatment biopsies to assess CRLX101 (cyclodextrin-based polymer-camptothecin CRLX101) nanoparticle and 20(S)-Camptothecin (CPT) uptake in tumor and normal tissue.

SECONDARY OBJECTIVES:

I. To evaluate the safety and toxicity of CRLX101 in this patient population.

II. To examine the antitumor efficacy of CRLX101 in advanced gastric/gastroesophageal junction (GEJ)/esophageal squamous or adenocarcinoma including clinical benefit rate (complete response [CR] + partial response [PR] + stable disease [SD]) at 4 months and overall survival.

OUTLINE:

Patients receive cyclodextrin-based polymer-camptothecin CRLX101 intravenously (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.

Patients achieving stable disease or better, may receive treatment for an additional 6 months.

After completion of study treatment, patients are followed up monthly.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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
  • All subjects must have the ability to understand and the willingness to sign a written informed consent
  • Subjects must not have received prior chemotherapy or radiation within < 4 weeks prior to first dose of study drug
  • Subjects may be entered if they have received prior radiation therapy involving =< 30% of the bone marrow; any prior radiation therapy must have been administered >= 4 weeks prior to first dose of study drug and the subject must be recovered from the acute toxic effects of the treatment prior to first dose of study drug (defined as a return to baseline or a severity of =< grade 1)
  • Subjects may be enrolled with a history of treated brain metastases that are clinically stable for >= 4 weeks prior to the first dose of study drug; subjects may not be currently receiving dexamethasone

Exclusion Criteria:

  • Patients with adenocarcinoma histology and documented HER2 overexpression
  • 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
  • Subjects with marked baseline prolongation of QT/QTc interval (for females QTc interval >= 470 msec and for males QTc interval >= 450 msec)
  • Subjects, who in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01612546

Locations
United States, California
City of Hope Medical Center Recruiting
Duarte, California, United States, 91010
Contact: Joseph Chao, MD    800-826-4673      
Principal Investigator: Joseph Chao, MD         
Sponsors and Collaborators
City of Hope Medical Center
Investigators
Principal Investigator: Joseph Chao City of Hope Medical Center
  More Information

No publications provided

Responsible Party: City of Hope Medical Center
ClinicalTrials.gov Identifier: NCT01612546     History of Changes
Other Study ID Numbers: 11276, NCI-2012-00893
Study First Received: June 4, 2012
Last Updated: August 1, 2014
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Additional relevant MeSH terms:
Esophageal Neoplasms
Carcinoma, Squamous Cell
Adenocarcinoma
Stomach Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Head and Neck Neoplasms
Esophageal Diseases
Camptothecin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 19, 2014