Quinacrine-Capecitabine Combinatorial Therapy for Advanced Stage Colorectal Adenocarcinoma

NCT01844076 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: GI-078
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

Establish the tolerability and safety of aimed dose of both quinacrine and capecitabine in combination to treat patients with advanced colorectal adenocarcinoma.

Conditions

Colorectal Adenocarcinoma

Keywords

advanced stage colorectal adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• 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).

  One year

Secondary Outcomes (1)

• Phase II - Rate of Response

  2-3 years

Other Outcomes (1)

• Phase II - Time to Progression (TTP)

  2-3 years

Study Arms (4)

Phase I Level -2

EXPERIMENTAL

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

Drug: Quinacrine and Capecitabine

Phase I Level -1

EXPERIMENTAL

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

Drug: Quinacrine and Capecitabine

Phase I Level 0

EXPERIMENTAL

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

Drug: Quinacrine and Capecitabine

Phase II

EXPERIMENTAL

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

Drug: Quinacrine and Capecitabine

Interventions

Quinacrine and Capecitabine DRUG

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.

Also known as: Quinacrine, Capecitabine

Phase I Level -1; Phase I Level -2; Phase I Level 0; Phase II

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Fox Chase Cancer Center: lead

Study Sites (1)

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19011, United States

Location

MeSH Terms

Interventions

Quinacrine; Capecitabine

Intervention Hierarchy (Ancestors)

Aminoacridines; Acridines; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Limitations and Caveats

Uncertain optimal time of peak plasma concentrations due to sample measurements at only 4 time points. Inaccurate half-life of Cmax due to lack of samples. Technical errors for lower-than-expected concentrations in participants.

Results Point of Contact

• Title: Crystal Denlinger MD, FACP
• Organization: Fox Chase Cancer Center

Crystal.Denlinger@fccc.edu

215-214-1676

Study Officials

• Crystal S. Denlinger, MD

  Fox Chase Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 4, 2013
• First Posted: May 1, 2013
• Study Start: January 14, 2016
• Primary Completion: August 9, 2019
• Study Completion: August 9, 2019
• Last Updated: March 25, 2021
• Results First Posted: March 25, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)