FOLFOX/Bevacizumab/Hydroxychloroquine (HCQ) in Colorectal Cancer

NCT01206530 | Completed Phase 1 DMC

• 1 other identifier: UPCC 07210
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

In this Phase I/II clinical trial, the investigators seek to pilot the addition of hydroxychloroquine (HCQ) to the standard front-line therapy of colorectal cancer, FOLFOX/bevacizumab. In toxicity terms, the investigators previous studies lead them to believe that a full dose (800mg) of HCQ will be well-tolerated in this setting. By starting at 600 mg, the investigators will ensure that the full dose is approached with an eye to safety, and if needed, the investigators will use the lower dose. Both doses achieve autophagy inhibition in our current studies.

Conditions

Rectal Cancer; Colon Cancer; Metastasis; Adenocarcinoma

Keywords

histologically documented; advanced; metastatic; adenocarcinoma; colon; rectum

Outcome Measures

Primary Outcomes (1)

• Response Rate

  We will use response as the primary efficacy marker to investigate the relationship between changes in autophagy markers and SUVs and the efficacy of treatment.

Secondary Outcomes (3)

• Progression-free survival

• Overall survival

• Incidence of toxicity

Interventions

Hydroxychloroquine DRUG

Dose:600 or 800 mg Route:PO daily Treatment Administration: Daily

Oxaliplatin DRUG

Dose: 85mg/m2 Route: IV infusion over 2 hours Treatment Administration: Day 1

Leucovorin DRUG

Dose: 400mg/m2 Route IV infusion over 2 hours Treatment Administration: Day 1

5-fluorouracil DRUG

Dose: 400mg/m2 Route: IV bolus immediately following leucovorin Treatment Administration Day 1

Bevacizumab DRUG

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 documented advanced or metastatic adenocarcinoma of the colon or rectum.
• Patients must have measurable disease as defined by the RECIST criteria as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as 20 mm with conventionaltechniques on either CT of MRI. Marker (CEA) elevation alone is insufficient for entry.
• Patients may have had prior adjuvant treatment of advanced colorectal cancer. The prior treatment regimen must not have included bevacizumab but may have included oxaliplatin and the last dose of chemotherapy must have been 6 months prior to study entry. Patients with prior radiotherapy are acceptable. It must be at least 2 weeks since administration of radiation therapy and all signs of toxicty must have abated.
• Patients must be 18 years or older.
• Patients must have an ECOG performance status of 0-1.
• The following required Initial Laboratory Values should be obtained within 4 weeks of the start of treatment: Granulocytes 1,500/ml, Platelet Count 100,000/ml, Creatinine 1.5 x upper limit of normal, Bilirubin 1.5 x upper limit of normal, AST 5 x upper limit of normal Urine Urine protein:creatinine ratio 1.0 at screening
• Patients must not be pregnant or lactating as chemotherapy is thought to present substantial risk to the fetus/infant.
• Patients must have a life expectancy of greater than three months.
• Patients must have the ability to understand and the willingness to sign a written informed consent document.

You may not qualify if:

• Major sugical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, anticipation of need for major surgical procedure during the course of the study. Minor surgical procedures such as fine needle aspirations or core biopsies within 7 days prior to Day 0.
• Patients with serious nonhealing wounds, ulcers, or bone fractures.
• Patients with a history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months prior to Day 0
• Patients with a history of myocardial infarction, unstable angina, or cerebrovascular accident 6 months prior to registration.
• Patients with clinically significant peripheral vascular disease.
• Patients with New York Heart Association Class II or greater congestive heart failure (class II is defined as symptoms of fatigue, dyspnea or other symptoms with ordinary physical activity).
• Patients using oral or parenteral anticoagulation are not excluded provided they are on a stable dose of anticoagulant.
• Patients with pre-existing hypertension should be on a stable antihypertensive regimen and have a blood pressure 150/100 mmHg at the time of enrollement.
• Patients must not have known brain metastases because the study drug has not been adequately tested in this setting.

Sponsors & Collaborators

• Abramson Cancer Center at Penn Medicine: lead

Study Sites (1)

Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (1)

• Mendonca Gorgulho C, Krishnamurthy A, Lanzi A, Galon J, Housseau F, Kaneno R, Lotze MT. Gutting it Out: Developing Effective Immunotherapies for Patients With Colorectal Cancer. J Immunother. 2021 Feb-Mar 01;44(2):49-62. doi: 10.1097/CJI.0000000000000357.

  PMID: 33416261 DERIVED

MeSH Terms

Conditions

Rectal Neoplasms; Colonic Neoplasms; Neoplasm Metastasis; Adenocarcinoma

Interventions

Hydroxychloroquine; Oxaliplatin; Leucovorin; Fluorouracil; Bevacizumab

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases; Colonic Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coordination Complexes; Organic Chemicals; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Peter J. O'Dwyer, MD

  Abramson Cancer Center at Penn Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Purpose: TREATMENT
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 16, 2010
• First Posted: September 22, 2010
• Study Start: September 1, 2010
• Primary Completion: September 1, 2017
• Study Completion: September 1, 2017
• Last Updated: April 18, 2019

Record last verified: 2019-04

Locations

US (1)