Protective Effect of Pentoxifylline Against Chemotherapy Induced Toxicities in Patients With Colorectal Cancer

NCT05590117 | Unknown Early Phase 1 FDA Drug

• 1 other identifier: 35931/10/22
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to: \- Evaluate the possible protective effect of pentoxifylline against oxaliplatin induced peripheral neuropathy and chemotherapy induced mucositis in patients with stage II and stage III colorectal cancer. This study will be a randomized placebo controlled parallel study.48 patients with colorectal cancer will be randomized to 2 groups: Group I (control group; n=24) which will receive 12 cycles of FOLFOX-6 regimen plus placebo tablets twice daily. Group II (Pentoxiphylline group; n=24) which will receive FOLFOX-6 regimen in addition to pentoxifylline 400 mg twice daily. Blood sample collection and biochemical assessment:

• Malondialdehyde (MDA) as oxidative stress marker (colorimetry).
• Tumor necrosis factor alfa (TNF-α) as pro inflammatory marker (ELISA).
• Neurotensin (NT) as a potential marker for neuropathic pain (ELISA).
• Citrulline as a biomarker for mucositis (ELISA). Clinical assessment of oxaliplatin induced neuropathy will be done through: The assessment of the severity of neuropathic pain through "Brief Pain Inventory-Short Form" at baseline and by the end of every two chemotherapy cycles. The implication of National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE, Version 5, 2017) for grading of neuropathy every 2 cycles. The use of Neurotoxicity- 12 item questionnaire score (Ntx-12) from the validated Functional Assessment of Cancer Therapy/Gynecologic Oncology Group at baseline and by the end of every two chemotherapy cycles). Mucositis will be assessed at baseline and by the end of every two chemotherapy cycles through the use of common terminology criteria for adverse events "CTCAE, version 5.00, 2017

Conditions

Colo-rectal Cancer; Neuropathy;Peripheral; Mucositis

Keywords

Colorectal cancer; Neuropathy; Mucositis; Pentoxifylline; Chemotherapy; Toxicity

Outcome Measures

Primary Outcomes (3)

• percentage of patients with peripheral sensory neuropathy grade ≥ 2

  Grading according to National Cancer Institute Common Terminology. there are 5 grades; Grade (1) is asymptomatic may be accompanied by loss of tendon reflex or paresthesia. Grade (2) is moderate symptoms which limit instrumental activities of daily life Grade (3) is severe symptoms which limit self-care activates of daily life. Grade (4) is life threatening consequences or urgent intervention indicated. Grade (5) is death. Criteria for Adverse Events (NCI-CTCAE, Version 5, 2017)

  6 months

• variation of 12-item neurotoxicity questionnaire (Ntx- 12) total score

  the Ntx-12 questionnaire is comprised of 12 statements intended to measure the severity and impact of peripheral sensory neuropathy on patients' lives. Patients will be instructed to complete the Arabic version of the Ntx-12 and choose the number corresponding to how true each statement was for them using a likert-type scale, with 0 indicating not at all; 1, a little bit; 2, somewhat; 3, quite a bit; and 4, very much

  6 months

• variation in grades of mucositis

  Mucositis will be assessed through the use of common terminology criteria for adverse events "CTCAE, version 5.00, 2017". Grade (1) is Asymptomatic or mild symptoms; intervention not indicated. Grade (2) is Moderate pain or ulcer that does not interfere with oral intake; modified diet indicated. Grade (3) is Severe pain, interfering with oral intake. Grade (4) is Life-threatening consequences; urgent intervention indicated. Grade (5) is Death.

  6 months

Secondary Outcomes (4)

• Change in the biological marker Malondialdehyde

  6 months

• Change in the biological marker Tumor necrosis factor alfa

  6 months

• Change in the biological marker Neurotensin

  6 months

• Change in the biological marker Citrulline

  6 months

Study Arms (2)

Group 1 placebo

PLACEBO COMPARATOR

n=24 which will receive 12 cycles of FOLFOX-6 regimen plus placebo tablets twice daily.

Drug: Placebo; Drug: FOLFOX-6 regimen

Group 2 pentoxifylline

ACTIVE COMPARATOR

n=24 which will receive FOLFOX-6 regimen in addition to pentoxifylline 400 mg twice daily.

Drug: Pentoxifylline; Drug: FOLFOX-6 regimen

Interventions

Pentoxifylline DRUG

Pentoxifylline is a potent anti inflammatory may prevent chemotherapy induced neuropathy and mucositis and will be administered 400mg twice daily

Also known as: Trental

Group 2 pentoxifylline

Placebo DRUG

placebo tablets

Group 1 placebo

FOLFOX-6 regimen DRUG

12 cycles of FOLFOX-6 regimen

Also known as: Oxaliplatin, Fluorouracil, calcium leucovorin

Group 1 placebo; Group 2 pentoxifylline

Eligibility Criteria

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

You may qualify if:

• \- Patients with histologically confirmed diagnosis of stage II and stage III colorectal cancer.
• Patients who will be scheduled to receive FOLFOX-6 regimen.
• Patients with no contraindication to chemotherapy.
• Males and females aged ≥ 18 years old.
• Adequate baseline hematologic values (absolute neutrophilic count ≥ 1.5
• × 109/L, platelet count ≥ 100 × 109/L and hemoglobin level ≥ 10 g/dl).
• Patients with adequate renal function (serum creatinine \< 1.5 mg/dL and Creatinine clearance (ClCr) ˃ 45 mL/min).
• Patients with adequate liver function (serum bilirubin \< 1.5 mg/dl).
• Patients with performance status \< 2 according to Eastern Cooperative Oncology Group (ECOG) score.

You may not qualify if:

• \- Children \< 18 years old.
• Prior exposure to neurotoxic chemotherapy (oxaliplatin, cisplatin, vincristine, paclitaxel, docetaxel or Isoniazid) for at least 6 months prior the study treatment.
• Evidence of pre-existing peripheral neuropathy resulting from another reason (diabetes, brain tumor or brain trauma).
• Patients with diabetes and other conditions that predispose to neuropathy as hypothyroidism, autoimmune diseases or hepatitis C.
• History of known allergy to oxaliplatin or other platinum agents.
• Patients with other inflammatory diseases (rheumatoid arthritis and ulcerative colitis) or stressful conditions (obesity class 2 and 3, smoking).
• Concomitant use of multivitamins (vitamins E, C and A), tricyclic antidepressants or other neuro-protective medications (gabapentin, lamotrigine, carbamazepine and phenytoin, etc...).
• Concurrent active cancer originating from a primary site other than colon or rectum.
• Patients on blood thinning agents
• Pregnant and breastfeeding women

Sponsors & Collaborators

• Tanta University: lead

Study Sites (1)

Tanta University

Tanta, Gharbyia, 00000, Egypt

Location

Related Publications (20)

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MeSH Terms

Conditions

Colonic Neoplasms; Neuritis; Mucositis; Colorectal Neoplasms

Interventions

Pentoxifylline; Oxaliplatin; Fluorouracil; Leucovorin

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Gastroenteritis; Mouth Diseases; Stomatognathic Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Theobromine; Xanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coordination Complexes; Organic Chemicals; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Coenzymes; Enzymes and Coenzymes

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 13, 2022
• First Posted: October 21, 2022
• Study Start: October 11, 2022
• Primary Completion: October 11, 2023
• Study Completion: October 11, 2024
• Last Updated: October 21, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

EG (1)