Symptoms and General Pathology

All Conditions

Neoplasms

Digestive System Diseases

Mouth and Tooth Diseases

Rare Diseases

Recurrence

Esophageal Neoplasms

Carcinoma

Carcinoma, Squamous Cell

Head and Neck Neoplasms

Mouth Neoplasms

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Esophageal Diseases

Mouth Diseases

Stomatognathic Diseases

Esophageal Cancer

Oral Cancer

Antineoplastic Agents

All Drugs and Chemicals

Vasodilator Agents

Urological Agents

Nivolumab

Pembrolizumab

Immunomodulating Agents

Tadalafil

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Phosphodiesterase 5 Inhibitors

Phosphodiesterase Inhibitors

Enzyme Inhibitors

Tadalafil for up to 12 months and pembrolizumab for up to 24 months.

Khushbu Singh

Joseph Califano

This study will examine the combination of pembrolizumab and tadalafil for safety and efficacy in advanced head and neck cancer.

Immune competent animal models of HNSCC demonstrate that combination PDE-5 inhibitor (tadalafil) and PD-1 inhibitor therapy is more effective than either therapy alone based on the concept of targeting multiple immune repressive abnormalities simultaneously (PD-1 checkpoint and myeloid suppressive pathways).

This trial will test the hypothesis that combination PD-1 inhibition and PDE-5 inhibition can be safely co-administered, and secondarily test the hypothesis that the combination of both therapies will be more effective than PD-1 inhibition alone in recurrent/metastatic HNSCC.

Tadalafil and Pembrolizumab in Recurrent or Metastatic Head and Neck Cancer

A Phase II Study of Tadalafil and Pembrolizumab in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

Rate of dose limiting toxicity at least possibly attributable to study treatment

Overall survival at 12 months post-enrollment

University of California, San Diego

Professor of Medicine

Paclitaxel

Albumin-Bound Paclitaxel

Cetuximab

Cisplatin

Tubulin Modulators

Antimitotic Agents

NIVOTAX (nivolumab + paclitaxel, follow by maintenance with nivolumab)

ERBITAX (cetuximab + paclitaxel, follow by maintenance with cetuximab)

Combination treatment: Nivolumab 240 mg will be administered via IV infusion every 2 weeks. Paclitaxel 80mg/m2 will be administered via IV infusion weekly. After 12 weeks from the start of the combined treatment paclitaxel will be stopped.

Maintenance treatment with nivolumab 480 mg every 4 weeks will start two weeks after the last administration of nivolumab 240 mg. Once nivolumab is administered at 480 mg, paclitaxel can no longer be administered.

Nivolumab will be continued alone until disease progression, unacceptable toxicity or withdrawal of consent up to a maximum of 24 months.

Nivolumab + Paclitaxel

Combination treatment: Cetuximab 250 mg/m2 (first dose of 400 mg/m2) administered via IV infusion weekly plus weekly paclitaxel (80 mg/m2) administered via IV infusion.

After 12 weeks from the start of the combined treatment paclitaxel will be stopped and weekly cetuximab will be continued alone until disease progression, unacceptable toxicity or withdrawal of consent up to a maximum of 24 months.

Cetuximab + Paclitaxel

Ricard Mesia, MD

Lara Iglesias, MD

Chemotherapy for recurrent or metastatic head and neck squamous cell carcinoma is palliative and usually platinum based, and the patients often present with poor physical condition. Consequently, many of them are not able to withstand a platinum-based chemotherapy. The addition of taxanes to the armamentarium of drugs improve the outcome in this group of patients. An alternative and better tolerated regimen for these patients is paclitaxel in combination with cetuximab, included the in guidelines of the Spanish Society of Medical Oncology.

Recently, new treatments such as immune-checkpoint inhibitors have shown promising activity and good tolerability in patients with recurrent or metastatic head and neck squamous cell carcinoma and has been included in the recently published guidelines from the Society for Immunotherapy of Cancer. Nivolumab (anti-PD1) has been approved for patients progressing on or after platinum-based therapy, as it clearly impacts on overall survival.

This randomized phase II study will evaluate the efficacy of nivolumab plus paclitaxel for first-line treatment of recurrent or metastatic HNSCC in the platinum ineligible and platinum refractory settings. Control arm will be paclitaxel in combination with cetuximab, treatment included in the guidelines of the Spanish Society of Medical Oncology.

Study to Assess the Efficacy and Safety of Nivolumab in Combination With Paclitaxel in Subjects With Head and Neck Cancer Unable for Cisplatin-based Chemotherapy (NIVOTAX)

Phase II Multicenter Randomized Trial to Assess the Efficacy and Safety of First Line Nivolumab in Combination With Paclitaxel in Subjects With R/M HNSCC Unable for Cisplatin-based Chemotherapy (NIVOTAX)

OS is defined as the time between the date of randomization and the date of death. For subjects without documentation of death, OS will be censored on the last date the subject was known to be alive.

PFS is defined as the time from randomization to the date of first documented disease progression, as assessed by the investigator using RECIST 1.1 criteria, or death due to any cause, whichever occurs first.

ORR is defined as the number of subjects with a best overall response (BOR) of a complete response (CR) or partial response (PR) divided by the number of randomized subjects for each treatment group.

Disease control rate (DCR) is defined as the number of subjects with a best overall response (BOR) of a complete response (CR), partial response (PR) or stable disease (SD) divided by the number of randomized subjects for each treatment group.

Duration of Response (DoR) is defined as the time between the date of first confirmed response to the date of the first documented tumor progression (per RECIST 1.1), or death due to any cause, whichever occurs first.

Rate of PD is defined as the number of subjects with PD at 6 months divided by the number of randomized subjects for each treatment group.

OS is defined as the time between the date of randomization and the date of death.

Percentage of patients with AEs in relation with total number of treated patients

Percentage of patients with Grade 3 and Grade 4 AEs in relation with total number of treated patients

Percentage of patients with SAEs in relation with total number of treated patients

Percentage of patients who discontinued due to AEs in relation with total number of treated patients

Percentage of patients with each AE by grade in relation with total number of treated patients

Bristol-Myers Squibb

Apices Soluciones S.L.

Grupo Español de Tratamiento de Tumores de Cabeza y Cuello

Patients enrolled in Arm A will receive IPI-549 40 mg by mouth daily for at least 14 days

40mg by mouth (PO) every day (QD) for at least 14 days

IPI-549

Debanjali Ghosh, MA

Elaine Eng

Ezra Cohen, MD

The purpose of this study is to investigate how effective the study drug IPI-549 is against types of cancers. IPI-549 is considered experimental because it is not approved by the US Food and Drug Administration (FDA) for the treatment of cancer.

Patients will be treated with 2 weeks of IPI-549, a specific PI3Kγ inhibitor. Tumor tissue for research purposes through core biopsies will be obtained prior to initiation of IPI-549 and at surgery.

This is a phase 2 window of opportunity trial in patients with locally advanced head and neck cancer. A key objective is to provide the first proof that macrophage phenotype switching can be accomplished in humans and lay the groundwork for future trials of this novel approach to immune therapy. Patients who are candidates for surgical resection will be enrolled and treated with 2 weeks of IPI-549, a specific PI3Kγ inhibitor. Tumor tissue for research purposes through core biopsies will be obtained prior to initiation of IPI-549 and at surgery.

The study team hypothesizes that mRNA signatures of immune response will be increased in IPI-549-treated patients. For the efficacy endpoints, RECISTv1.1 will be used.

Window of Opportunity Study of IPI-549 in Patients With Locally Advanced HPV+ and HPV- Head and Neck Squamous Cell Carcinoma

Phase 2 Window of Opportunity Study of IPI-549 in Patients With Locally Advanced HPV+ and HPV- Head and Neck Squamous Cell Carcinoma

To detect IPI-549-induced changes in PI3Kγ-regulated signatures of immune suppression.

Compare pre- vs. post-treatment tumor tissue

T cell receptor (TCR) sequencing at baseline, surgery, end of treatment or at time of disease progression.

To determine safety and tolerability of IPI-549 and change in tumor size in patients with locally advanced HNSCC

The V Foundation for Cancer Research

Ezra Cohen

Skin and Connective Tissue Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Nervous System Diseases

Breast Neoplasms

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Peripheral Nervous System Diseases

Endometrial Neoplasms

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Neuromuscular Diseases

Uterine Neoplasms

Uterine Diseases

Ovarian Cancer

Ovarian Epithelial Cancer

Micronutrients

Lipid Regulating Agents

Hematinics

Vitamins

Niacinamide

Niacin

Nicotinic Acids

Folic Acid

Vitamin B Complex

Trace Elements

Hypolipidemic Agents

Antimetabolites

Nicotinamide

Nicotinic Acid

Vitamin B3

Folate

Vitamin B9

Daily oral administration of nicotinamide riboside 300 mg (150 mg a.m. and p.m.) for one week with dose escalation to 1000 mg (500 mg a.m. and p.m.) for remaining 11 weeks.

Nicotinamide Riboside

Donna L Hammond, PhD

Alexandra Thomas, MD

The purpose of this single-arm phase II trial is to determine whether nicotinamide riboside (NIAGEN®) prevents the progression of peripheral sensory neuropathy in patients receiving infusions of paclitaxel or nab-paclitaxel for the treatment of metastatic breast cancer or recurrent platinum-resistant ovarian, endometrial, peritoneal, fallopian tube cancer or metastatic head and neck cancer.

Peripheral neuropathies are a dose-limiting, disabling, and debilitating side effect of virtually every known class of chemotherapeutic agent, and are referred to as chemotherapy-induced peripheral neuropathies (CIPN) (Seretny et al., 2014). The incidence and severity of CIPN increase as the cumulative dose, frequency of administration, and the number of therapeutic cycles increase. As many as 68% of patients have CIPN when assessed within 30 days of completing treatment. Patients experience paresthesias, dysesthesias (an unpleasant abnormal sensation, whether spontaneous or evoked), hyperalgesia (increased pain from a stimulus that normally provokes pain), allodynia (pain due to a stimulus that does not normally provoke pain), numbness or loss of sensation, or ongoing pain that is burning, lancinating or electric shock-like in nature. CIPN can seriously diminish a patient's quality of life, and can interfere with self-care and activities of daily living. The severity of CIPN may also necessitate reducing the dose of chemotherapeutic agent, delaying the next cycle of chemotherapy, or terminating treatment entirely (Argyriou et al., 2012; Argyriou et al., 2014; Miltenburg et al., 2014; Park et al., 2013).

Nicotinamide adenine dinucleotide (NAD+) is an essential redox coenzyme required for cell viability, basic bioenergetics, and fast axonal transport (Yang and Sauve, 2016). It plays an important role in protection against axonal injury from either mechanical or neurotoxic injury (Araki et al., 2004; Sasaki et al., 2006; Sasaki et al., 2009; Gerdts et al., 2015; Khan et al., 2014; Conforti et al., 2014; Di Stefano et al., 2015). Nicotinamide riboside (NIAGEN®) is a form of vitamin B3 and a precursor in the pathway for synthesis of NAD+ (Bieganowski et al., 2004; Trammell et al., 2016; Chi and Sauve, 2013). Oral administration of NIAGEN® increases levels of NAD+ in the blood, liver, skeletal muscle, and other tissues (Canto et al., 2012; Hamity et al, 2017; Airhart et al., 2017; Martens et al., 2018).

NIAGEN®) has been reported to prevent tactile hypersensitivity and blunt the affective dimension of nociception in a rat model of CIPN (Hamity et al., 2017) It also prevents signs of peripheral neuropathy in a mouse model of diabetes (Trammell et al., 2016) The proposed single-arm pilot phase II study will examine whether daily dosing with NIAGEN®) can prevent the progression of CIPN in persons with stage IV breast cancer or recurrent platinum-resistant ovarian, endometrial, peritoneal, or fallopian tube cancer receiving once weekly infusions of paclitaxel for 12 weeks.

In this study, persons with metastatic breast cancer, platinum-resistant recurrent ovarian, peritoneal, endometrial, or fallopian tube cancer, or platinum-resistant recurrent or metastatic head and neck cancer who are receiving weekly infusions of paclitaxel or nab-paclitaxel and anticipated to survive for at least 3 months will be offered the opportunity to enroll in this study when they develop a peripheral neuropathy of at least grade 1. Persons with peripheral neuropathy of no greater than a grade 2 from prior therapy may also enroll in this study if they are receiving weekly infusions of paclitaxel or nab-paclitaxel. Upon enrollment, health care providers will review the overall severity of the participant's neuropathy and assign a baseline grade. Participants will also complete two short questionnaires that will more specifically score how the peripheral neuropathy interferes with daily functions of living. A small sample of blood will be taken at the completion of the paclitaxel or nab-paclitaxel infusion to measure levels of paclitaxel. The participant will then be sent home with capsules of NIAGEN® to take twice daily. Each week upon return to the clinic a small sample of blood will be taken before the infusion of paclitaxel to measure biomarkers for NIAGEN®, and other samples of blood will be taken to evaluate clinical chemistries, kidney, and liver function. Another sample of blood will be obtained after the paclitaxel or nab-paclitaxel infusion to measure levels of paclitaxel or nab-paclitaxel. The health care provider will meet with the patient each week to score the overall severity of the peripheral neuropathy, and the participant will answer another questionnaire with more specific questions. Once a month, the participant will be asked to fill out a second questionnaire. Participants will take 300 mg/day NIAGEN® in the first week and 1000 mg/day in the subsequent 11 weeks. The study will conclude one week after the 12th infusion of paclitaxel or nab-paclitaxel. Health care providers will contact the participant at various times up to 6 months to monitor their status.

Beginning with completion of the trial by the 10th participant and continuing with each subsequent participant up to 39, we will use a Bayesian statistical approach (Lee and Liu, 2008; i.e. predictive probability) to determine whether NIAGEN® has prevented a worsening of the peripheral neuropathy. This approach we let us make an early determination of futility. We will also determine whether NIAGEN® has decreased the need to delay or diminish the doses of paclitaxel or nab-paclitaxel due to severity of the peripheral neuropathy. The results of this trial will inform the design of a subsequent randomized, placebo-controlled, blinded clinical trial.

All subjects with stage IV breast cancer, platinum-resistant recurrent ovarian, peritoneal, endometrial, or fallopian tube cancer, or platinum-resistant recurrent or metastatic head and neck cancer will receive 300 mg NIAGEN®) daily for one week followed by dose escalation to 1000 mg daily for 11 weeks upon reporting the development of grade 1 sensory neuropathy. Those presenting with a residual sensory neuropathy of ≤ 2 as a result of prior chemotherapy will also be enrolled.

NR in Chemo-induced Peripheral Neuropathy

Nicotinamide Riboside (NR) in Paclitaxel-induced Peripheral Neuropathy

All of the individual participant data collected during the trial, after de-identification, will be shared with researchers who provide a methodologically sound proposal to achieve aims in the approved proposal. The IPD will be available to sharing immediately after publication and ending 5 years after article publication

Exploratory analysis of ability of the clinical version of the Total Neuropathy Score questionnaire to detect changes in CIPN severity over time. Unlike the CTCAE or the FACT\&GOG-NTX questionnaires, the TNS is a patient reported outcome measure. HIghest score (worse neuropathy is 24, lowest score is 0. Outcome assessed difference between end of treatment and screening. A positive number indicates improvement in neuropathy

The primary outcome variable is defined as no worsening of the grade of peripheral sensory neuropathy as scored according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 guidelines. Per the CTCAE a score of 1 would be assigned in the instance of parethesias or a loss of deep tendon reflexes. A score of 2 would be assigned in the instance of moderate symptoms that limit instrumental activities of daily living. A score of 3 would be assigned in the instance of severe symptoms that limit self-care activities of daily living. Because the outcome measure is defined as no worsening of the grade, it was recorded as either "yes"( i.e. it worsened) or "no" (i.e. it did not worsen).

Quantitate the percentage of patients that experience a dose reduction of paclitaxel or nab-paclitaxel therapy due to neuropathy.

Count the number of (i.e. the incidence) of dose reduction events due to neuropathy (each occasion of dose reduction is a separate event);

Quantitate the total cumulative dose of paclitaxel administered over the 12 weeks.

Difference in Score on the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - neurotoxicity questionnaire at the end of treatment; i.e. Score at screening - score at end of treatment. This questionnaire asks 11 questions that are specific to chemotherapy-induced peripheral neuropathies. Maximum score is 44, minimum score is 0. Positive differences indicate a decrease in neuropathy. Negative differences indicate a worsening of neuropathy. Zero means unchanged.

National Cancer Institute (NCI)

ChromaDex, Inc.

Donna Hammond, PhD

Professor

Subjects were queried for adverse events by phone interview 1, 3 and 6 months after end of treatment.

Daily oral administration of nicotinamide riboside 300 mg (150 mg a.m. and p.m.) for one week with dose escalation to 1000 mg (500 mg a.m. and p.m.) for remaining 11 weeks.

Nicotinamide Riboside: Capsule

NIAGEN®)

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Plasma sample obtained before NIAGEN treatment begun

NAD concentration plasma levels

Plasma samples obtained before NIAGEN treatment begun

1-methyl-nicotinamide plasma levels

Plasma sample obtained 10-20 min after taxane infusion ended

one sample not submitted due to subject testing COVID positive and withdrawing from study

paclitaxel plasma levels

This trial was limited to a non-curative population of women receiving taxane chemotherapy without added platinum-based agents. Difficulty in recruiting this small population led to eventual termination of the trial. Dose escalation to 1000 mg/day did not occur for any subject due to physician concerns that subjects were not tolerating the 300 mg dose well.

Donna L. Hammond, Ph.D Professor

Data are reported for the 4 subjects who took at least one dose of NIAGEN. End of treatment was originally defined as within 2 weeks after 12 weeks of NIAGEN treatment ended (i.e. a study duration of \~14 weeks). If a patient withdrew before completing 12 weeks of treatment, the end of treatment was designated as one week after withdrawal from the study. The longest that any participant was on NIAGEN was three weeks. Therefore, the time frame of the study has been adjusted to \~4 weeks.

Number of Participants With No Worsening in the Grade of Peripheral Sensory Neuropathy as Scored by CTCAE

Data are reported for the only subject who received more than 1 dose of taxane chemotherapy before withdrawal from the trial. That subject patient received only 2 doses of taxane over a period of 3 weeks. No patient completed the full 12 weeks of the trial. Therefore, the time frame of the study has been adjusted from the originally envisioned 12 weeks to \~3 weeks.

Percentage of Patients in Which Dose of Paclitaxel or Nab-Paclitaxel is Reduced Due to CIPN

Data are reported for the only subject who received more than 1 dose of taxane chemotherapy before withdrawal from the trial. That patient received only 2 doses of taxane over a period of 3 weeks. The original aim was to assess dose reduction over the 12 weeks of paclitaxel treatment, but no patient completed the 12 weeks of treatment. As the longest that any patient was on NIAGEN was 3 weeks, the time frame has been adjusted accordingly.

Number of Dose Reduction Events

Data are reported for the 1 subject who received taxane infusions after starting NIAGEN treatment. They received 2 infusions over a period of three weeks of NIAGEN treatment.

Total Dose of Paclitaxel Administered

Data are reported for the three subjects who took at least one dose of NIAGEN and completed the FACT questionnaire. End of treatment was originally defined as within 2 weeks after 12 weeks of NIAGEN treatment ended (i.e. a study duration of \~ 14 weeks). If a patient withdrew before then, the end of treatment was designated as one week after withdrawal. Unfortunately, the longest that any patient was on NIAGEN was three weeks. Therefore, the time frame has been adjusted to \~4 weeks.

Difference in Score Between Baseline and End of Treatment for the FACT&GOG-NTX Subscale .

Data are reported for the three subjects who took at least one dose of NIAGEN and completed the TNS evaluation. No patient completed the full 12 weeks of the trial. Therefore, the measure was made at end of treatment, which was designated as one week after they ceased NIAGEN treatment. The longest any one patient was on NIAGEN was three weeks. Hence the time frame was adjusted to 4 weeks.

Difference in Total Neuropathy Score Between Screening and End of Treatment

Paclitaxel levels in plasma were measured \~30 min after each infusion of taxane. This was undertaken to ascertain whether NIAGEN altered plasma levels of paclitaxel because increases or decreases in plasma levels of paclitaxel by itself could lead to an apparent worsening or improvement, respectively, in CIPN and confound interpretation of NIAGEN's effect.

Data are reported for three subjects in which paclitaxel levels were obtained before NIAGEN and after NIAGEN treatment, which ranged from one to three weeks. The plasma concentration for the last blood sample obtained after NIAGEN treatment

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Tadalafil and Pembrolizumab in Recurrent or Metastatic Head and Neck Cancer	NCT03993353	Head and Neck C... Head and Neck S... Head and Neck C... Head and Neck C... Head and Neck C... Head and Neck C... Cancer Cancer of Esoph... Cancer, Metasta... Cancer of Head ... Cancer of Mouth Cancer of Neck	Pembrolizumab Tadalafil	18 Years -	University of California, San Diego
Study to Assess the Efficacy and Safety of Nivolumab in Combination With Paclitaxel in Subjects With Head and Neck Cancer Unable for Cisplatin-based Chemotherapy (NIVOTAX)	NCT04282109	Recurrent Head ... Head and Neck C...	Nivolumab + Pac... Cetuximab + Pac...	18 Years -	Grupo Español de Tratamiento de Tumores de Cabeza y Cuello
Window of Opportunity Study of IPI-549 in Patients With Locally Advanced HPV+ and HPV- Head and Neck Squamous Cell Carcinoma	NCT03795610	Head and Neck S... Head and Neck C... Head and Neck C... Head and Neck C... Head and Neck C... HPV-Related Car... HPV-Related Mal... HPV-Related Squ...	IPI-549	18 Years -	University of California, San Diego
NR in Chemo-induced Peripheral Neuropathy	NCT03642990	Chemotherapy-in... Breast Cancer M... Platinum-resist... Head and Neck C... Endometrial Can...	Nicotinamide Ri...	18 Years - 85 Years	University of Iowa
NR in Chemo-induced Peripheral Neuropathy	NCT03642990	Chemotherapy-in... Breast Cancer M... Platinum-resist... Head and Neck C... Endometrial Can...	Nicotinamide Ri...	18 Years - 85 Years	University of Iowa

Spots Global Cancer Trial Database for head and neck cancer stage iv