Colo-rectal CancerEarly Phase 1NCT05590117
Protective Effect of Pentoxifylline Against Chemotherapy Induced Toxicities in Patients With Colorectal Cancer
A Early Phase 1 study testing Pentoxifylline and FOLFOX-6 regimen in people with Colo-rectal Cancer and Neuropathy;Peripheral, run by Tanta University at 1 site in Egypt.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colo-rectal Cancer, Neuropathy;Peripheral, Mucositis
- What is being tested?
- Pentoxifylline and FOLFOX-6 regimen
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 48 participants
- Where
- 1 siteEgypt
- Study dates
- 11 Oct 2022to 11 Oct 2024
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
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 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).
Show all 9Show fewer
- 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.
Who cannot join
- - 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).
Show all 10Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Possible Protective Effect of Pentoxifylline Against Chemotherapy Induced Toxicities in Patients With Colorectal Cancer
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.
Read more
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
Read the detailed description
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. Assessment of participants' adherence, side effects and tolerability Pentoxiphylline will be provided on biweekly basis and the participants' adherence will be assessed through counting the returned tablets. Participants will be followed-up by weekly telephone calls and direct meetings during chemotherapy cycles to assess their adherence and to report any drug related adverse effects. The adverse effects will be collected and graded according to the National Cancer Institute Common Terminology Criteria for Adverse events "NCI-CTCAE; version 5, 2017". Participants will be considered non- adherent and excluded from the study if not consumed the provided tablets or lost the follow-up meeting at any time of intervention or changed regimen.
The primary and secondary endpoints:
The primary endpoint is the percentage of patients with peripheral sensory neuropathy grade ≥ 2, the variation of 12-item neurotoxicity questionnaire (Ntx- 12) total score and the variation in grades of mucositis. The secondary endpoint is the change in the serum concentrations of the measured biological markers.
Sample size calculation:
According to the results of previous studies, the total number of subjects required to detect the effect of neuro-protective drugs in patients received neuro- toxic chemotherapy was 41 patients with 5% significance, 80% statistical power and an attrition of 15 %. In this context, during the current study, a total sample size of 41 patients in both arms will be sufficient to detect the effect. Assuming that the attrition rate will be 15 %, the initial sample size will be 48 patients in both arms with 24 patients in each arm.
Ethical approval:
The study will be performed in accordance with the ethical standards of Helsinki declaration in 1964 and its later amendments. The study will be approved by the Research Ethics Committee of Tanta University. The study will be registered as a clinical trial at ClinicalTrials.gov. All participants will be informed about the benefits and risks of the study. Any unexpected risks that will appear during the course of the research will be clarified to the participants and to the ethical committee on time. The data of the enrolled patients will be confidential. All enrolled patients will give their written informed consents. The study will be conducted between October 2022 and October 2024.
- Conditions
- Colo-rectal Cancer, Neuropathy;Peripheral, Mucositis
- Being tested
- Pentoxifylline, Placebo, FOLFOX-6 regimen
- Keywords
- Colorectal cancer, Neuropathy, Mucositis, Pentoxifylline, Chemotherapy, Toxicity
- Medical subject headings
- Colonic Neoplasms, Neuritis, Mucositis, Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PentoxifyllineDrug
Also called Trental
Pentoxifylline is a potent anti inflammatory may prevent chemotherapy induced neuropathy and mucositis and will be administered 400mg twice daily
PlaceboDrug
placebo tablets
FOLFOX-6 regimenDrug
Also called Oxaliplatin, Fluorouracil, calcium leucovorin
12 cycles of FOLFOX-6 regimen
| Study group | Role | What they receive |
|---|---|---|
| Group 1 placebo | Placebo comparator | n=24 which will receive 12 cycles of FOLFOX-6 regimen plus placebo tablets twice daily. Receives: 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. Receives: Drug: Pentoxifylline; Drug: FOLFOX-6 regimen |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 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
Measured: 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.
Measured: 6 months
Secondary outcomes (4)
Change in the biological marker Malondialdehyde
Malondialdehyde (MDA) as oxidative stress marker will be measured using colorimetry
Measured: 6 months
Change in the biological marker Tumor necrosis factor alfa
Tumor necrosis factor alfa (TNF-α) as pro inflammatory marker will be measured using ELISA will be measured using (ELISA).
Measured: 6 months
Change in the biological marker Neurotensin
Neurotensin (NT) as a potential marker for neuropathic pain will be measured using ELISA
Measured: 6 months
Change in the biological marker Citrulline
Citrulline as a biomarker for mucositis will be measured using ELISA
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Oct 2022
- Study start11 Oct 2022 (estimated)
- Primary completion11 Oct 2023 (estimated)
- Study completion11 Oct 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (20)Papers the sponsor has linked to this study.
- Other trials for Colo-rectal CancerStudies of the same condition, open and under way.
- More trials run by Tanta UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 48 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Tanta University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mostafa Tarek Aboelnoor, Tanta University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05590117
- Sponsor's protocol ID
- 35931/10/22
- Status last verified
- Oct 2022
- First submitted
- 13 Oct 2022
- Last updated
- 21 Oct 2022
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Keum N, Giovannucci E. Global burden of colorectal cancer: emerging trends, risk factors and prevention strategies. Nat Rev Gastroenterol Hepatol. 2019 Dec;16(12):713-732. doi: 10.1038/s41575-019-0189-8. Epub 2019 Aug 27.
PubMed 31455888Guren MG. The global challenge of colorectal cancer. Lancet Gastroenterol Hepatol. 2019 Dec;4(12):894-895. doi: 10.1016/S2468-1253(19)30329-2. Epub 2019 Oct 21. No abstract available.
PubMed 31648973Andre T, Iveson T, Labianca R, Meyerhardt JA, Souglakos I, Yoshino T, Paul J, Sobrero A, Taieb J, Shields AF, Ohtsu A, Grothey A, Sargent DJ; for the IDEA Steering Committee. The IDEA (International Duration Evaluation of Adjuvant Chemotherapy) Collaboration: Prospective Combined Analysis of Phase III Trials Investigating Duration of Adjuvant Therapy with the FOLFOX (FOLFOX4 or Modified FOLFOX6) or XELOX (3 versus 6 months) Regimen for Patients with Stage III Colon Cancer: Trial Design and Current Status. Curr Colorectal Cancer Rep. 2013;9(3):261-269. doi: 10.1007/s11888-013-0181-6.
PubMed 24032000Zedan AH, Hansen TF, Fex Svenningsen A, Vilholm OJ. Oxaliplatin-induced neuropathy in colorectal cancer: many questions with few answers. Clin Colorectal Cancer. 2014 Jun;13(2):73-80. doi: 10.1016/j.clcc.2013.11.004. Epub 2013 Nov 13.
PubMed 24365057Saito Y, Okamoto K, Kobayashi M, Narumi K, Furugen A, Yamada T, Iseki K. Magnesium co-administration decreases cisplatin-induced nephrotoxicity in the multiple cisplatin administration. Life Sci. 2017 Nov 15;189:18-22. doi: 10.1016/j.lfs.2017.08.028. Epub 2017 Aug 31.
PubMed 28864226Hoff PM, Saad ED, Costa F, Coutinho AK, Caponero R, Prolla G, Gansl RC. Literature review and practical aspects on the management of oxaliplatin-associated toxicity. Clin Colorectal Cancer. 2012 Jun;11(2):93-100. doi: 10.1016/j.clcc.2011.10.004. Epub 2011 Dec 6.
PubMed 22154408Zanardelli M, Micheli L, Cinci L, Failli P, Ghelardini C, Di Cesare Mannelli L. Oxaliplatin neurotoxicity involves peroxisome alterations. PPARgamma agonism as preventive pharmacological approach. PLoS One. 2014 Jul 18;9(7):e102758. doi: 10.1371/journal.pone.0102758. eCollection 2014.
PubMed 25036594Chakraborty A, Chowdhury S, Bhattacharyya M. Effect of metformin on oxidative stress, nitrosative stress and inflammatory biomarkers in type 2 diabetes patients. Diabetes Res Clin Pract. 2011 Jul;93(1):56-62. doi: 10.1016/j.diabres.2010.11.030. Epub 2010 Dec 13.
PubMed 21146883Kleczkowska P, Lipkowski AW. Neurotensin and neurotensin receptors: characteristic, structure-activity relationship and pain modulation--a review. Eur J Pharmacol. 2013 Sep 15;716(1-3):54-60. doi: 10.1016/j.ejphar.2013.03.004. Epub 2013 Mar 14.
PubMed 23500196Plaza-Manzano G, Molina-Ortega F, Lomas-Vega R, Martinez-Amat A, Achalandabaso A, Hita-Contreras F. Changes in biochemical markers of pain perception and stress response after spinal manipulation. J Orthop Sports Phys Ther. 2014 Apr;44(4):231-9. doi: 10.2519/jospt.2014.4996. Epub 2014 Jan 22.
PubMed 24450367Al Moundhri MS, Al-Salam S, Al Mahrouqee A, Beegam S, Ali BH. The effect of curcumin on oxaliplatin and cisplatin neurotoxicity in rats: some behavioral, biochemical, and histopathological studies. J Med Toxicol. 2013 Mar;9(1):25-33. doi: 10.1007/s13181-012-0239-x.
PubMed 22648527Basile D, Di Nardo P, Corvaja C, Garattini SK, Pelizzari G, Lisanti C, Bortot L, Da Ros L, Bartoletti M, Borghi M, Gerratana L, Lombardi D, Puglisi F. Mucosal Injury during Anti-Cancer Treatment: From Pathobiology to Bedside. Cancers (Basel). 2019 Jun 20;11(6):857. doi: 10.3390/cancers11060857.
PubMed 31226812Fragkos KC, Forbes A. Citrulline as a marker of intestinal function and absorption in clinical settings: A systematic review and meta-analysis. United European Gastroenterol J. 2018 Mar;6(2):181-191. doi: 10.1177/2050640617737632. Epub 2017 Oct 12.
PubMed 29511548Yehia R, Saleh S, El Abhar H, Saad AS, Schaalan M. L-Carnosine protects against Oxaliplatin-induced peripheral neuropathy in colorectal cancer patients: A perspective on targeting Nrf-2 and NF-kappaB pathways. Toxicol Appl Pharmacol. 2019 Feb 15;365:41-50. doi: 10.1016/j.taap.2018.12.015. Epub 2018 Dec 25.
PubMed 30592963Speer EM, Dowling DJ, Ozog LS, Xu J, Yang J, Kennady G, Levy O. Pentoxifylline inhibits TLR- and inflammasome-mediated in vitro inflammatory cytokine production in human blood with greater efficacy and potency in newborns. Pediatr Res. 2017 May;81(5):806-816. doi: 10.1038/pr.2017.6. Epub 2017 Jan 10.
PubMed 28072760
Study at a glance
From the registry record, last updated by the sponsor on 21 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Possible Protective Effect of Pentoxifylline Against Chemotherapy Induced Toxicities in Patients With Colorectal Cancer
- ClinicalTrials.gov ID
- NCT05590117
- Acronym / sponsor ID
- 35931/10/22
- Conditions
- Colo-rectal Cancer, Neuropathy;Peripheral, Mucositis
- Keywords
- Colorectal cancer, Neuropathy, Mucositis, Pentoxifylline, Chemotherapy, Toxicity
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 48 participants (estimated)
- Lead sponsor
- Tanta UniversityUniversity, hospital or other
- Study start
- 11 Oct 2022 (estimated)
- Primary completion
- 11 Oct 2023 (estimated)
- Study completion
- 11 Oct 2024 (estimated)
- First posted
- 21 Oct 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed description
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. Assessment of participants' adherence, side effects and tolerability Pentoxiphylline will be provided on biweekly basis and the participants' adherence will be assessed through counting the returned tablets. Participants will be followed-up by weekly telephone calls and direct meetings during chemotherapy cycles to assess their adherence and to report any drug related adverse effects. The adverse effects will be collected and graded according to the National Cancer Institute Common Terminology Criteria for Adverse events "NCI-CTCAE; version 5, 2017". Participants will be considered non- adherent and excluded from the study if not consumed the provided tablets or lost the follow-up meeting at any time of intervention or changed regimen.
The primary and secondary endpoints:
The primary endpoint is the percentage of patients with peripheral sensory neuropathy grade ≥ 2, the variation of 12-item neurotoxicity questionnaire (Ntx- 12) total score and the variation in grades of mucositis. The secondary endpoint is the change in the serum concentrations of the measured biological markers.
Sample size calculation:
According to the results of previous studies, the total number of subjects required to detect the effect of neuro-protective drugs in patients received neuro- toxic chemotherapy was 41 patients with 5% significance, 80% statistical power and an attrition of 15 %. In this context, during the current study, a total sample size of 41 patients in both arms will be sufficient to detect the effect. Assuming that the attrition rate will be 15 %, the initial sample size will be 48 patients in both arms with 24 patients in each arm.
Ethical approval:
The study will be performed in accordance with the ethical standards of Helsinki declaration in 1964 and its later amendments. The study will be approved by the Research Ethics Committee of Tanta University. The study will be registered as a clinical trial at ClinicalTrials.gov. All participants will be informed about the benefits and risks of the study. Any unexpected risks that will appear during the course of the research will be clarified to the participants and to the ethical committee on time. The data of the enrolled patients will be confidential. All enrolled patients will give their written informed consents. The study will be conducted between October 2022 and October 2024.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 1 placebo | Placebo comparator | Drug: Placebo, Drug: FOLFOX-6 regimenn=24 which will receive 12 cycles of FOLFOX-6 regimen plus placebo tablets twice daily. |
| Group 2 pentoxifylline | Active comparator | Drug: Pentoxifylline, Drug: FOLFOX-6 regimenn=24 which will receive FOLFOX-6 regimen in addition to pentoxifylline 400 mg twice daily. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- - 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
Key exclusion criteria (10 listed)
- - 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PentoxifyllineAlso: TrentalPentoxifylline is a potent anti inflammatory may prevent chemotherapy induced neuropathy and mucositis and will be administered 400mg twice daily | Drug | Group 2 pentoxifylline |
| Placeboplacebo tablets | Drug | Group 1 placebo |
| FOLFOX-6 regimenAlso: Oxaliplatin, Fluorouracil, calcium leucovorin12 cycles of FOLFOX-6 regimen | Drug | Group 1 placebo, Group 2 pentoxifylline |
Primary outcome
percentage of patients with peripheral sensory neuropathy grade ≥ 2
Time frame: 6 months
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)
variation of 12-item neurotoxicity questionnaire (Ntx- 12) total score
Time frame: 6 months
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
variation in grades of mucositis
Time frame: 6 months
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.
4 secondary outcomes
Change in the biological marker Malondialdehyde
Time frame: 6 months
Change in the biological marker Tumor necrosis factor alfa
Time frame: 6 months
Change in the biological marker Neurotensin
Time frame: 6 months
Change in the biological marker Citrulline
Time frame: 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Oct 2022.
- Background: PubMed 31455888Keum N, Giovannucci E. Global burden of colorectal cancer: emerging trends, risk factors and prevention strategies. Nat Rev Gastroenterol Hepatol. 2019 Dec;16(12):713-732. doi: 10.1038/s41575-019-0189-8. Epub 2019 Aug 27.
- Background: PubMed 31648973Guren MG. The global challenge of colorectal cancer. Lancet Gastroenterol Hepatol. 2019 Dec;4(12):894-895. doi: 10.1016/S2468-1253(19)30329-2. Epub 2019 Oct 21. No abstract available.
- Background: PubMed 24032000Andre T, Iveson T, Labianca R, Meyerhardt JA, Souglakos I, Yoshino T, Paul J, Sobrero A, Taieb J, Shields AF, Ohtsu A, Grothey A, Sargent DJ; for the IDEA Steering Committee. The IDEA (International Duration Evaluation of Adjuvant Chemotherapy) Collaboration: Prospective Combined Analysis of Phase III Trials Investigating Duration of Adjuvant Therapy with the FOLFOX (FOLFOX4 or Modified FOLFOX6) or XELOX (3 versus 6 months) Regimen for Patients with Stage III Colon Cancer: Trial Design and Current Status. Curr Colorectal Cancer Rep. 2013;9(3):261-269. doi: 10.1007/s11888-013-0181-6.
- Background: PubMed 24365057Zedan AH, Hansen TF, Fex Svenningsen A, Vilholm OJ. Oxaliplatin-induced neuropathy in colorectal cancer: many questions with few answers. Clin Colorectal Cancer. 2014 Jun;13(2):73-80. doi: 10.1016/j.clcc.2013.11.004. Epub 2013 Nov 13.
- Background: PubMed 28864226Saito Y, Okamoto K, Kobayashi M, Narumi K, Furugen A, Yamada T, Iseki K. Magnesium co-administration decreases cisplatin-induced nephrotoxicity in the multiple cisplatin administration. Life Sci. 2017 Nov 15;189:18-22. doi: 10.1016/j.lfs.2017.08.028. Epub 2017 Aug 31.
- Background: PubMed 22154408Hoff PM, Saad ED, Costa F, Coutinho AK, Caponero R, Prolla G, Gansl RC. Literature review and practical aspects on the management of oxaliplatin-associated toxicity. Clin Colorectal Cancer. 2012 Jun;11(2):93-100. doi: 10.1016/j.clcc.2011.10.004. Epub 2011 Dec 6.
- Background: PubMed 25036594Zanardelli M, Micheli L, Cinci L, Failli P, Ghelardini C, Di Cesare Mannelli L. Oxaliplatin neurotoxicity involves peroxisome alterations. PPARgamma agonism as preventive pharmacological approach. PLoS One. 2014 Jul 18;9(7):e102758. doi: 10.1371/journal.pone.0102758. eCollection 2014.
- Background: PubMed 21146883Chakraborty A, Chowdhury S, Bhattacharyya M. Effect of metformin on oxidative stress, nitrosative stress and inflammatory biomarkers in type 2 diabetes patients. Diabetes Res Clin Pract. 2011 Jul;93(1):56-62. doi: 10.1016/j.diabres.2010.11.030. Epub 2010 Dec 13.
- Background: PubMed 23500196Kleczkowska P, Lipkowski AW. Neurotensin and neurotensin receptors: characteristic, structure-activity relationship and pain modulation--a review. Eur J Pharmacol. 2013 Sep 15;716(1-3):54-60. doi: 10.1016/j.ejphar.2013.03.004. Epub 2013 Mar 14.
- Background: PubMed 24450367Plaza-Manzano G, Molina-Ortega F, Lomas-Vega R, Martinez-Amat A, Achalandabaso A, Hita-Contreras F. Changes in biochemical markers of pain perception and stress response after spinal manipulation. J Orthop Sports Phys Ther. 2014 Apr;44(4):231-9. doi: 10.2519/jospt.2014.4996. Epub 2014 Jan 22.
- Background: PubMed 22648527Al Moundhri MS, Al-Salam S, Al Mahrouqee A, Beegam S, Ali BH. The effect of curcumin on oxaliplatin and cisplatin neurotoxicity in rats: some behavioral, biochemical, and histopathological studies. J Med Toxicol. 2013 Mar;9(1):25-33. doi: 10.1007/s13181-012-0239-x.
- Background: PubMed 31226812Basile D, Di Nardo P, Corvaja C, Garattini SK, Pelizzari G, Lisanti C, Bortot L, Da Ros L, Bartoletti M, Borghi M, Gerratana L, Lombardi D, Puglisi F. Mucosal Injury during Anti-Cancer Treatment: From Pathobiology to Bedside. Cancers (Basel). 2019 Jun 20;11(6):857. doi: 10.3390/cancers11060857.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Pentoxifylline and FOLFOX-6 regimen in people with Colo-rectal Cancer and Neuropathy;Peripheral, run by Tanta University at 1 site in Egypt.
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 9 inclusion and 10 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: status not confirmed, as of the sponsor's last update on 21 Oct 2022. 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 Egypt. 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. Some participants in this study may receive a placebo. 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
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?
percentage of patients with peripheral sensory neuropathy grade ≥ 2 (time frame: 6 months). The study lists 3 primary outcomes in all. 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 NCT05590117, which also lists 20 linked publications.
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 21 Oct 2022.