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Adenocarcinoma of the EsophagusPhase 2NCT01612546

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

A Phase 2 study testing cyclodextrin-based polymer-camptothecin CRLX101, Laboratory biomarker analysis and Pharmacological studies in people with Adenocarcinoma of the Esophagus and Adenocarcinoma of the Gastroesophageal Junction, run by City of Hope Medical Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
cyclodextrin-based polymer-camptothecin CRLX101, Laboratory biomarker analysis and Pharmacological studies
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
10 participants
Where
1 siteUnited States
Study dates
Nov 2012to 15 Jan 2015
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • City of Hope Medical Center

    Duarte, California, 91010

Other trials in United States

About this study

Official title: Pilot Trial of CRLX101 in the Treatment of Patients With Advanced Gastric, Gastroesophageal, or Esophageal Squamous or Adenocarcinoma

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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.

Being tested
cyclodextrin-based polymer-camptothecin CRLX101, Laboratory biomarker analysis, Pharmacological studies
Medical subject headings
Adenocarcinoma Of Esophagus, Esophageal Neoplasms, Stomach Neoplasms, Esophageal Squamous Cell Carcinoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • cyclodextrin-based polymer-camptothecin CRLX101Drug

    Also called CRLX101, cyclodextrin-based polymer-camptothecin IT-101, IT-101

    Given IV

  • Laboratory biomarker analysisOther

    Correlative studies

  • Pharmacological studiesOther

    Correlative studies

Study groups in NCT01612546
Study groupRoleWhat they receive
Treatment (cyclodextrin-based polymer-camptothecin CRLX101)ExperimentalPatients 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.
Receives: Drug: cyclodextrin-based polymer-camptothecin CRLX101; Other: Laboratory biomarker analysis; Other: Pharmacological studies

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Baseline and day 8

Secondary outcomes (4)

  1. Overall Objective Response Rate

    Patients with best response of Complete Response or Partial Response assessed using Response Evaluation Criteria In Solid Tumors (RECIST) 1.1. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

    Measured: Up to 4 years

  2. Clinical Benefit Rate

    Patients with a best response of Complete Response, Partial Response or Stable Disease after at least 4 months of treatment assessed using Response Evaluation Criteria In Solid Tumors (RECIST) 1.1. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), not a CR, PR, Progression or Symptomatic Deterioration; Progression (PD), a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Symptomatic Deterioration, global deterioration of health status requiring discontinuation of treatment without objective evidence of progression. Clinical Benefit (CR + PR +SD≥4months).

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

  3. Overall Survival

    Estimated using the product-limit method of Kaplan and Meier.

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

  4. Incidence of Adverse Events

    Incidence of treatment related adverse events graded per NCI CTCAE version 4.03

    Measured: Up to 4 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Jun 2012 (estimated)
  2. Study startNov 2012
  3. Primary completion15 Jan 2015
  4. Study completion15 Jan 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01612546
Sponsor's protocol ID
11276
Other IDs
NCI-2012-00893
Status last verified
Jan 2018
First submitted
4 Jun 2012
Last updated
1 Feb 2018
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing cyclodextrin-based polymer-camptothecin CRLX101, Laboratory biomarker analysis and Pharmacological studies in people with Adenocarcinoma of the Esophagus and Adenocarcinoma of the Gastroesophageal Junction, run by City of Hope Medical Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Dec 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

CRLX101 (CPT) Uptake in Tumor and Nearby Normal Tissue (time frame: Baseline and day 8). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01612546.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Feb 2018.

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