Back to resultsQuinacrine-Capecitabine Combinatorial Therapy for Advanced Stage Colorectal Adenocarcinoma
Primary Purpose
Colorectal Adenocarcinoma
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Quinacrine and Capecitabine
Sponsored by
About this trial
This is an interventional treatment trial for Colorectal Adenocarcinoma focused on measuring advanced stage colorectal adenocarcinoma
Eligibility Criteria
Inclusion Criteria:
- Patients much have histologically confirmed adenocarcinoma of the colon or rectum.
- Patients must have measurable recurrence or metastases in the liver and/or lungs.
- Patients must have prior chemotherapy for advanced colorectal cancer and have previously received both an oxaliplatin and an irinotecan based regimen.
- Age > 18 years.
- Life expectancy greater than 4 weeks.
- ECOG performance status <3.
- Patients must have normal organ and marrow function.
- Patients must be able to swallow capsules.
- Patients must be able to understand and willing to sign a written informed consent document.
- Patients are included regardless of KRAS/BRAF status.
Exclusion Criteria:
- Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
- Patients may not be receiving any other investigational agent.
- Patients with know brain metastases should be excluded from this clinical trial because they often develop progressive neurological dysfunction that would confound the evaluation of neurologic and other adverse events.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to quinacrine, capecitabine or fluorouracil.
- The concomitant use of quinacrine and primaquine is contraindicated.
- Uncontrolled intercurrent illness including but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnant women are excluded from this study.
- Patients with a baseline creatinine clearance of < 50 mL/min.
- Patients must be currently not treated with quinacrine or drugs related to quinacrine.
- Patients who require anti-arrhythmic treatment with amiodarone or any drug with a quinidine-like effect on the heart or who have history of a malignant ventricular arrhythmia unless they have a functioning automatic implantable cardio defibrillator implanted.
- Patients who have a history of noninfectious hepatitis or alcoholism.
- Patients with a lifetime history of porphyria or psoriasis because it can exacerbate these conditions.
- Patients with documented glucose-6-phosphate dehydrogenase deficiency.
- Patients with a lifetime history of seizure disorder.
- Patients with a lifetime history of dermatitis as an allergic/toxic reaction to any medication.
- Patients with know dihydropyrimidine dehydrogenase deficiency.
Sites / Locations
- Fox Chase Cancer Center
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Phase I Level -2
Phase I Level -1
Phase I Level 0
Phase II
Arm Description
Phase I (Quinacrine and Capecitabine): The Phase I portion of the study will aim to determine the tolerability of both agents in combinations when used at established clinical doses. This portion of the study will more closely resemble a pilot study or feasibility study rather than a dose escalation. Each group will have 1 to 6 patients enrolled in it. If the patients in a lower group do not have any significant side effects the next patient will start at the next group dose. Group 1: capecitabine at a dose of 1000 mg/m^2 twice per day (days 1-14), and quinacrine at a dose of 100 mg once per day (days 1-21) for a 21 day cycle
Phase I (Quinacrine and Capecitabine): The Phase I portion of the study will aim to determine the tolerability of both agents in combinations when used at established clinical doses. This portion of the study will more closely resemble a pilot study or feasibility study rather than a dose escalation. Each group will have 1 to 6 patients enrolled in it. If the patients in a lower group do not have any significant side effects the next patient will start at the next group dose. Group 1: capecitabine at a dose of 1000 mg/m^2 twice per day (days 1-14), and quinacrine at a dose of 100 mg twice per day (days 1-21) for a 21 day cycle
Group 3: capecitabine at a dose of 1000 mg/m^2 twice per day (days 1-14), quinacrine at a dose of 200 mg twice a day (days 1-21) for a 21 day cycle
Phase II will use the treatment outlined in phase I, using the recommended phase II dose (RP2D) derived from Phase I. Patients will receive capecitabine at a dose of 1000 mg/m^2 twice per day (days 1-14), quinacrine at a dose of 100 mg twice per day (days 1-21) for a 21 day cycle
Outcomes
Primary Outcome Measures
Phase I - Number of Participants Who Experienced Dose Limiting Toxicities and Adverse Reactions
Establish the tolerability of both agents in combination when used at established clinical doses. The objective is to determine toxicities and adverse reactions of patients in each group with different dose levels to find the maximum tolerated dose (MTD).
Secondary Outcome Measures
Phase II - Rate of Response
Determine rate of response in patients receiving quinacrine in combination with capecitabine. Using Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) complete response (CR) is a disappearance of all target lesions, partial response (PR) is at least 30% decrease in the sum of diameters of target lesions, and overall response is the number of patients who experience a complete response or partial response.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01844076
Brief Title
Quinacrine-Capecitabine Combinatorial Therapy for Advanced Stage Colorectal Adenocarcinoma
Official Title
Quinacrine-Capecitabine Combinatorial Therapy for Advanced Stage Colorectal Adenocarcinoma:A Phase I/II Investigator-Initiated Clinical Trial
Study Type
Interventional
2. Study Status
Record Verification Date
March 2021
Overall Recruitment Status
Terminated
Why Stopped
The single Quinacrine manufacture facility in the US was shut down by the FDA
Study Start Date
January 14, 2016 (Actual)
Primary Completion Date
August 9, 2019 (Actual)
Study Completion Date
August 9, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fox Chase Cancer Center
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Establish the tolerability and safety of aimed dose of both quinacrine and capecitabine in combination to treat patients with advanced colorectal adenocarcinoma.
Detailed Description
Because of the well published safety profiles of both quinacrine and capecitabine, the Phase I portion of our study will aim to determine the tolerability of both agents in combinations when used at established clinical doses. This portion of the study will more closely resemble a pilot study or feasibility study rather than a dose escalation Phase I trial. The objective is to determine toxicities and adverse reactions, not a maximally tolerated dose. The investigators hypothesize that there will be no toxic interactions at the pharmacokinetic or pharmacodynamic level, and want to know the feasibility of using quinacrine and capecitabine at their respective recommended single agent doses. Because capecitabine is already regarded as standard treatment for colorectal cancer, the investigators will begin the study with a full dose of capecitabine combined with a slightly lower dose of quinacrine. If the safety-interim analysis does not detect an excess of toxicity, then subsequent patients will be enrolled using the full dose of both drugs.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Adenocarcinoma
Keywords
advanced stage colorectal adenocarcinoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
19 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Phase I Level -2
Arm Type
Experimental
Arm Description
Phase I (Quinacrine and Capecitabine): The Phase I portion of the study will aim to determine the tolerability of both agents in combinations when used at established clinical doses. This portion of the study will more closely resemble a pilot study or feasibility study rather than a dose escalation.
Each group will have 1 to 6 patients enrolled in it. If the patients in a lower group do not have any significant side effects the next patient will start at the next group dose.
Group 1: capecitabine at a dose of 1000 mg/m^2 twice per day (days 1-14), and quinacrine at a dose of 100 mg once per day (days 1-21) for a 21 day cycle
Arm Title
Phase I Level -1
Arm Type
Experimental
Arm Description
Phase I (Quinacrine and Capecitabine): The Phase I portion of the study will aim to determine the tolerability of both agents in combinations when used at established clinical doses. This portion of the study will more closely resemble a pilot study or feasibility study rather than a dose escalation.
Each group will have 1 to 6 patients enrolled in it. If the patients in a lower group do not have any significant side effects the next patient will start at the next group dose.
Group 1: capecitabine at a dose of 1000 mg/m^2 twice per day (days 1-14), and quinacrine at a dose of 100 mg twice per day (days 1-21) for a 21 day cycle
Arm Title
Phase I Level 0
Arm Type
Experimental
Arm Description
Group 3: capecitabine at a dose of 1000 mg/m^2 twice per day (days 1-14), quinacrine at a dose of 200 mg twice a day (days 1-21) for a 21 day cycle
Arm Title
Phase II
Arm Type
Experimental
Arm Description
Phase II will use the treatment outlined in phase I, using the recommended phase II dose (RP2D) derived from Phase I.
Patients will receive capecitabine at a dose of 1000 mg/m^2 twice per day (days 1-14), quinacrine at a dose of 100 mg twice per day (days 1-21) for a 21 day cycle
Intervention Type
Drug
Intervention Name(s)
Quinacrine and Capecitabine
Other Intervention Name(s)
Quinacrine, Capecitabine
Intervention Description
The Phase I portion of the study will aim to determine the tolerability of both agents in combinations when used at established clinical doses. This portion of the study will more closely resemble a pilot study or feasibility study rather than a dose escalation.
Primary Outcome Measure Information:
Title
Phase I - Number of Participants Who Experienced Dose Limiting Toxicities and Adverse Reactions
Description
Establish the tolerability of both agents in combination when used at established clinical doses. The objective is to determine toxicities and adverse reactions of patients in each group with different dose levels to find the maximum tolerated dose (MTD).
Time Frame
One year
Secondary Outcome Measure Information:
Title
Phase II - Rate of Response
Description
Determine rate of response in patients receiving quinacrine in combination with capecitabine. Using Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) complete response (CR) is a disappearance of all target lesions, partial response (PR) is at least 30% decrease in the sum of diameters of target lesions, and overall response is the number of patients who experience a complete response or partial response.
Time Frame
2-3 years
Other Pre-specified Outcome Measures:
Title
Phase II - Time to Progression (TTP)
Description
Determine time to progression from start of treatment in patients receiving quinacrine in combination with capecitabine. Using Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1), progression is defined as a 20% increase in sum of target lesions, with at least a 5 mm absolute increase.
Time Frame
2-3 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients much have histologically confirmed adenocarcinoma of the colon or rectum.
Patients must have measurable recurrence or metastases in the liver and/or lungs.
Patients must have prior chemotherapy for advanced colorectal cancer and have previously received both an oxaliplatin and an irinotecan based regimen.
Age > 18 years.
Life expectancy greater than 4 weeks.
ECOG performance status <3.
Patients must have normal organ and marrow function.
Patients must be able to swallow capsules.
Patients must be able to understand and willing to sign a written informed consent document.
Patients are included regardless of KRAS/BRAF status.
Exclusion Criteria:
Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
Patients may not be receiving any other investigational agent.
Patients with know brain metastases should be excluded from this clinical trial because they often develop progressive neurological dysfunction that would confound the evaluation of neurologic and other adverse events.
History of allergic reactions attributed to compounds of similar chemical or biologic composition to quinacrine, capecitabine or fluorouracil.
The concomitant use of quinacrine and primaquine is contraindicated.
Uncontrolled intercurrent illness including but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
Pregnant women are excluded from this study.
Patients with a baseline creatinine clearance of < 50 mL/min.
Patients must be currently not treated with quinacrine or drugs related to quinacrine.
Patients who require anti-arrhythmic treatment with amiodarone or any drug with a quinidine-like effect on the heart or who have history of a malignant ventricular arrhythmia unless they have a functioning automatic implantable cardio defibrillator implanted.
Patients who have a history of noninfectious hepatitis or alcoholism.
Patients with a lifetime history of porphyria or psoriasis because it can exacerbate these conditions.
Patients with documented glucose-6-phosphate dehydrogenase deficiency.
Patients with a lifetime history of seizure disorder.
Patients with a lifetime history of dermatitis as an allergic/toxic reaction to any medication.
Patients with know dihydropyrimidine dehydrogenase deficiency.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Crystal S. Denlinger, MD
Organizational Affiliation
Fox Chase Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fox Chase Cancer Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19011
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
Started study at new Institution
Learn more about this trial
Quinacrine-Capecitabine Combinatorial Therapy for Advanced Stage Colorectal Adenocarcinoma
We'll reach out to this number within 24 hrs