Phase 2 Study of Ropidoxuridine as a Radiation Sensitizing Agent During Radiotherapy in Patients With Newly Diagnosed IDH-Wildtype Glioblastoma With Unmethylated MGMT Promoter

This is a randomized, open-label, phase 2 study evaluating the safety and efficacy of oral ropidoxuridine as a radiation-sensitizing agent in patients with newly diagnosed wild-type isocitrate dehydrogenase glioblastoma with an unmethylated O6-methylguanine-DNA methyltransferase promoter, undergoing standard 60 Gy radiotherapy.

Start Date02 Sep 2024

Sponsor / Collaborator

Shuttle Pharmaceuticals, Inc.

NCT04406857 / TerminatedPhase 1IIT

A Phase 1 Study of IPdR in Combination With Capecitabine and Radiotherapy in Rectal Cancer

This phase I trial studies the side effects and best dose of ropidoxuridine and how well it works when added to the usual chemotherapy treatment (capecitabine) during radiation therapy for the treatment of patients with stage II-III rectal cancer. Ropidoxuridine may help radiation therapy work better by making cancer cells more sensitive to the radiation therapy. Chemotherapy drugs, such as capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. This study is being done to find out whether ropidoxuridine in addition to capecitabine and radiation therapy works better in treating patients with rectal cancer.

Start Date17 Mar 2021

Sponsor / Collaborator

National Cancer Institute

NCT02993146 / Active, not recruitingPhase 1IIT

Phase 1 and Pharmacology Study of Oral 5-Iodo-2-Pyrimidinone-2-Deoxyribose (IPdR) as a Prodrug for IUdR-Mediated Tumor Radiosensitization in Brain Metastases

This phase I trial studies the side effects and best dose of ropidoxuridine when given together with whole brain radiation therapy in treating patients with cancer that has spread to the brain (brain metastases). Ropidoxuridine may help whole brain radiation therapy work better by making cancer cells more sensitive to the radiation therapy.

Start Date08 May 2017

Sponsor / Collaborator

National Cancer Institute

100 Clinical Results associated with Ropidoxuridine

100 Translational Medicine associated with Ropidoxuridine

100 Patents (Medical) associated with Ropidoxuridine

Literatures (Medical) associated with Ropidoxuridine

01 Aug 2023·Cancer chemotherapy and pharmacology

A case report of typhlitis during novel use of ropidoxuridine-capecitabine-radiotherapy for treatment-naïve rectal cancer.

Article

Author: Kunos, Charles A ; Collins, Jerry M ; Piekarz, Richard ; Kinsella, Timothy J

BACKGROUNDRectal carcinomas are tumors that arise from the last 12 cm of the large intestine closest to the anus. They generally have a modest prognosis exacerbated by a high local recurrence rate if radiosensitizing chemotherapy is not given during radiotherapy. This case report discusses the clinical trial treatment of a patient with rectal adenocarcinoma by a new ropidoxuridine-capecitabine-radiotherapy combination. This case report is novel due to the patient's participation in an accelerated titration phase I clinical trial and the resultant rare adverse event of treatment-related sigmoid typhlitis.CASE PRESENTATIONThe patient was an 82-year-old female who noticed hematochezia and change in stool caliber over a period of 3 months. A rectal mass was identified by biopsy as a microsatellite stable adenocarcinoma. A planned total neoadjuvant treatment involved eight cycles of leucovorin calcium (folinic acid)-fluorouracil-oxaliplatin (mFOLFOX6) chemotherapy, followed by a clinical trial combination of ropidoxuridine-capecitabine-radiotherapy, prior to definitive surgery. The patient began daily intensity modulated pelvic radiotherapy with concurrent twice-daily oral ropidoxuridine and twice-daily oral capecitabine to be given over 6 weeks. After 14 days of ropidoxuridine-capecitabine-radiotherapy, the patient developed sigmoid typhlitis requiring a 10-day hospitalization and 14-day disruption of treatment. The patient died 27 days after the start of ropidoxuridine-capecitabine-radiotherapy. This adverse event was listed as a definite attribution to the ropidoxuridine-capecitabine treatment; pharmacokinetic and pharmacodynamic data showed low ropidoxuridine metabolite DNA incorporation and high capecitabine metabolite concentration. The accelerated titration phase I clinical trial has been subsequently closed to accrual (NCT04406857).CONCLUSIONSWe believe this case report demonstrates the decision-making process for terminating a phase I accelerated titration designed clinical trial. The report also presents the rare complication of sigmoid typhlitis as a treatment-attributed adverse event. In this case, a ropidoxuridine-capecitabine combination was used as an investigational radiosensitizing treatment now with a narrower future clinical development pathway.

15 Oct 2019·Clinical Cancer ResearchQ1 · MEDICINE

Phase I and Pharmacology Study of Ropidoxuridine (IPdR) as Prodrug for Iododeoxyuridine-Mediated Tumor Radiosensitization in Advanced GI Cancer Undergoing Radiation

Q1 · MEDICINE

Article

Author: Kunos, Charles ; Schumacher, Andrew ; Hill, Kimberly D. ; Rosati, Kayla ; Kinsella, Timothy ; Collins, Jerry M. ; DiPetrillo, Thomas ; Wiersma, Susan ; Vatkevich, John ; Safran, Howard ; Anderson, Lawrence W.

AbstractPurpose:Iododeoxyuridine (IUdR) is a potent radiosensitizer; however, its clinical utility is limited by dose-limiting systemic toxicities and the need for prolonged continuous infusion. 5-Iodo-2-pyrimidinone-2′-deoxyribose (IPdR) is an oral prodrug of IUdR that, compared with IUdR, is easier to administer and less toxic, with a more favorable therapeutic index in preclinical studies. Here, we report the clinical and pharmacologic results of a first-in-human phase I dose escalation study of IPdR + concurrent radiation therapy (RT) in patients with advanced metastatic gastrointestinal (GI) cancers.Patients and Methods:Adult patients with metastatic GI cancers referred for palliative RT to the chest, abdomen, or pelvis were eligible for study. Patients received IPdR orally once every day × 28 days beginning 7 days before the initiation of RT (37.5 Gy in 2.5 Gy × 15 fractions). A 2-part dose escalation scheme was used, pharmacokinetic studies were performed at multiple time points, and all patients were assessed for toxicity and response to Day 56.Results:Nineteen patients were entered on study. Dose-limiting toxicity was encountered at 1,800 mg every day, and the recommended phase II dose is 1,200 mg every day. Pharmacokinetic analyses demonstrated achievable and sustainable levels of plasma IUdR ≥1 μmol/L (levels previously shown to mediate radiosensitization). Two complete, 3 partial, and 9 stable responses were achieved in target lesions.Conclusions:Administration of IPdR orally every day × 28 days with RT is feasible and tolerable at doses that produce plasma IUdR levels ≥1 μmol/L. These results support the investigation of IPdR + RT in phase II studies.

01 Jun 2018·Nutrition ResearchQ4 · MEDICINE

Early dietary restriction in rats alters skeletal muscle tuberous sclerosis complex, ribosomal s6 and mitogen-activated protein kinase

Q4 · MEDICINE

Article

Author: Dai, Yun ; Shin, Bo-Chul ; Calkins, Kara L ; Devaskar, Sherin U ; Thamotharan, Shanthie ; Kalhan, Satish C

Intrauterine growth restriction is linked to decreased lean body mass and insulin resistance. The mammalian target of rapamycin (mTOR) regulates muscle mass and glucose metabolism; however, little is known about maternal dietary restriction and skeletal muscle mTOR in offspring. We hypothesized that early dietary restriction would decrease skeletal muscle mass and mTOR in the suckling rat. To test this hypothesis, ab libitum access to food or dietary restriction during gestation followed by postnatal cross-fostering to a dietary-restricted or ad libitum-fed rat dam during lactation generated 4 groups: control (CON), intrauterine dietary restricted (IUDR), postnatal dietary restricted (PNDR), and IUDR+PNDR (IPDR). At day 21, when compared to CON, the IUDR group demonstrated "catchup" growth, but no changes were observed in the mTOR pathway. Despite having less muscle mass than CON and IUDR (P < .001), in IPDR and PNDR rats mTOR remained unchanged. IPDR and PNDR (p)-tuberous sclerosis complex 2 was less than the IUDR group (P < .05). Downstream, IPDR's and PNDR's phosphorylated (p)-ribosomal s6 (rs6)/rs6 was less than that of CON (P < .05). However, male IPDR's and PNDR's p-mitogen activated protein kinase MAPK/MAPK was greater than CON (P < .05) without a change in p90 ribosomal s6 kinase (p90RSK). In contrast, in females, MAPK was unchanged, but IPDR p-p90RSK/p90RSK was less than CON (P = .01). In conclusion, IPDR and PNDR reduced skeletal muscle mass but did not decrease mTOR. In IPDR and PNDR, a reduction in tuberous sclerosis complex 2 may explain why mTOR was unchanged, whereas, in males, an increase in MAPK with a decrease in rs6 may suggest a block in MAPK signaling.

News (Medical) associated with Ropidoxuridine

30 Oct 2024

·www.globenewswire.com

Shuttle Pharma Completes Clinical Trial Site Enrollment for Phase 2 of Ropidoxuridine for Treatment of Patients with Glioblastoma

Oct. 28, 2024 -- Shuttle Pharmaceuticals Holdings, Inc. (Nasdaq: SHPH) (“Shuttle Pharma”), a discovery and development stage specialty pharmaceutical company focused on improving outcomes for cancer patients treated with radiation therapy (RT), announced today it has finalized agreements with all six of the planned site enrollment locations to administer the Phase 2 clinical trial of Ropidoxuridine for the treatment of patients with glioblastoma following the entry into agreements with Georgetown University Medical Center and UNC Medical Center. The Company previously entered agreements with UVA Cancer Center, John Theurer Cancer Center at Hackensack University Medical Center, Allegheny Health Network (AHN) Cancer Institute, and Miami Cancer Institute, part of Baptist Health South Florida. Patients are currently undergoing screening for enrollment in the trial. Ropidoxuridine (IPdR) is Shuttle Pharma's lead candidate radiation sensitizer for use in combination with RT to treat brain tumors (glioblastoma), a deadly malignancy of the brain with no known cure. Shuttle has received Orphan Drug Designation from the FDA for IPdR, providing potential marketing exclusivity upon first FDA approval for treatment of the disease. “We have successfully engaged all six of the planned clinical trial site locations to administer the Phase 2 clinical trial of Ropidoxuridine,” commented Shuttle Pharma's CEO, Anatoly Dritschilo, M.D. “All six locations are nationally recognized cancer centers that are most likely to treat IDH wild-type, methylation negative glioblastoma patients, the target of the clinical trial. Patients are currently being evaluated for enrollment, having signed consents for treatment, and are now in the process of being screened.” The Phase 2 clinical trial has begun enrolling patients with aggressive, IDH wild-type, methylation negative glioblastomas. Presently, radiation is the standard of care for this particular group of patients, but outcome studies have shown that more than half of the patients live for less than 12 months after diagnosis. Shuttle Pharma’s Phase 2 clinical trial will randomize 40 patients into two different dose groups (20 @ 1,200 mg/day and 20 @ 960 mg/day) to determine an optimal dose, which will then be continued to add 14 patients on the optimal dosage to reach the survival end-point for comparison to historical controls. The Company expects the trial to be completed over the next 18 to 24 months. Dr. Dritschilo continued, “An estimated 800,000 patients in the U.S. are treated with radiation therapy annually. According to the American Cancer Society and the American Society of Radiation Oncologists, about 50% of those patients receive radiation therapy with curative intent. The market opportunity for radiation sensitizers lies with the 400,000 patients treated to achieve cancer cures. The results of this trial will be important to the cancer community as we look for effective radiation sensitizers to increase cancer cure rates, prolong patient survival and improve quality of life for patients suffering from glioblastoma.” Founded in 2012 by faculty members of the Georgetown University Medical Center, Shuttle Pharma is a discovery and development stage specialty pharmaceutical company focused on improving the outcomes for cancer patients treated with radiation therapy (RT). Our mission is to improve the lives of cancer patients by developing therapies that are designed to maximize the effectiveness of RT while limiting the side effects of radiation in cancer treatment. Although RT is a proven modality for treating cancers, by developing radiation sensitizers, we aim to increase cancer cure rates, prolong patient survival and improve quality of life when used as a primary treatment or in combination with surgery, chemotherapy and immunotherapy. For more information, please visit our website at www.shuttlepharma.com. The content above comes from the network. if any infringement, please contact us to modify.

Orphan DrugRadiation Therapy

30 Oct 2024

·www.globenewswire.com

Shuttle Pharmaceuticals Holdings, Inc. Announces Pricing of $4.5 Million Public Offering Priced At-The-Market Under Nasdaq Rules

GAITHERSBURG, Md., Oct. 29, 2024 (GLOBE NEWSWIRE) -- Shuttle Pharmaceuticals Holdings, Inc. (Nasdaq: SHPH) (“Shuttle Pharma” or the “Company”), a discovery and development stage specialty pharmaceutical company focused on improving outcomes for cancer patients treated with radiation therapy (RT), today announced the pricing of its "reasonable best efforts" public offering with a health-care focused institutional investor for the purchase and sale of up to 2,950,820 shares of common stock (or pre-funded warrants in lieu thereof) and warrants to purchase up to 2,950,820 shares of common stock at a combined offering price of $1.525 per share and accompanying warrant, priced at-the-market under Nasdaq rules (the “Offering”). The Company expects to receive aggregate gross proceeds of approximately $4.5 million, before deducting placement agent fees and other offering expenses, and assuming no exercise of the warrants. The warrants will have an exercise price of $1.40 per share, will be exercisable immediately and will expire five years from the issuance date. The closing of the Offering is expected to occur on or about October 31, 2024, subject to the satisfaction of customary closing conditions. The Company intends to use the net proceeds from this Offering to fund IND-enabling and Phase I and II clinical trials of product candidates, including $2.3 million in payments that will be owed to Theradex Systems, Inc., the clinical research organization (CRO) supporting Shuttle Pharma’s Phase II clinical trials for radiation sensitizer Ropidoxuridine, and for working capital and general corporate purposes. A.G.P./Alliance Global Partners is acting as the lead placement agent for the Offering and Boustead Securities, LLC is acting as a co-placement agent for the Offering. The securities described above are being offered pursuant to a registration statement on Form S-1 (File No. 333-282231) previously filed with the Securities and Exchange Commission ("SEC") which was declared effective on October 29, 2024. This Offering is being made only by means of a prospectus forming part of the effective registration statement. A preliminary prospectus relating to the Offering has been filed with the SEC. An electronic copy of the final prospectus relating to the Offering may be obtained, when available, on the SEC's website located at http://www.sec.gov and may also be obtained from A.G.P./Alliance Global Partners, 590 Madison Avenue, 28th Floor, New York, NY 10022, or by telephone at (212) 624-2060, or by email at prospectus@allianceg.com. This press release shall not constitute an offer to sell or the solicitation of an offer to buy nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction. About Shuttle Pharmaceuticals Holdings, Inc. Founded in 2012 by faculty members of the Georgetown University Medical Center, Shuttle Pharma is a discovery and development stage specialty pharmaceutical company focused on improving the outcomes for cancer patients treated with radiation therapy (RT). Our mission is to improve the lives of cancer patients by developing therapies that are designed to maximize the effectiveness of RT while limiting the side effects of radiation in cancer treatment. Although RT is a proven modality for treating cancers, by developing radiation sensitizers, we aim to increase cancer cure rates, prolong patient survival and improve quality of life when used as a primary treatment or in combination with surgery, chemotherapy and immunotherapy. For more information, please visit our website at www.shuttlepharma.com. Safe Harbor Statements in this press release about future expectations, plans and prospects, as well as any other statements regarding matters that are not historical facts, may constitute “forward-looking statements.” These statements include, but are not limited to, statements concerning the development of our company, the satisfaction of customary closing conditions related to the Offering, the timing of the anticipated closing of the Offering and the intended use of proceeds from the Offering. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “will,” “would” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including factors discussed in the “Risk Factors” section of Shuttle Pharma’s Annual Report on Form 10-K for the year ended December 31, 2023, as amended, filed with the SEC on September 4, 2024, as well other SEC filings. Any forward-looking statements contained in this press release speak only as of the date hereof and, except as required by federal securities laws, Shuttle Pharmaceuticals specifically disclaims any obligation to update any forward-looking statement, whether as a result of new information, future events or otherwise. Shuttle PharmaceuticalsAnatoly Dritschilo, M.D., CEO240-403-4212info@shuttlepharma.com Investor ContactsLytham Partners, LLCRobert Blum602-889-9700 shph@lythampartners.com

Radiation TherapyPhase 2

29 Oct 2024

·www.globenewswire.com

Shuttle Pharma Doses First Patients in Phase 2 Clinical Trial of Ropidoxuridine for Treatment of Patients with Glioblastoma

GAITHERSBURG, Md., Oct. 29, 2024 (GLOBE NEWSWIRE) -- Shuttle Pharmaceuticals Holdings, Inc. (Nasdaq: SHPH) (“Shuttle Pharma”), a discovery and development stage specialty pharmaceutical company focused on improving outcomes for cancer patients treated with radiation therapy (RT), announced today that the first three patients in its Phase 2 Clinical Trial of Ropidoxuridine for the treatment of patients with glioblastoma have been successfully dosed. Ropidoxuridine (IPdR) is Shuttle Pharma's lead candidate radiation sensitizer for use in combination with RT to treat brain tumors (glioblastoma), a deadly malignancy of the brain with no known cure. Shuttle has received Orphan Drug Designation from the FDA, providing potential marketing exclusivity upon first FDA approval for the disease. The Phase 2 clinical trial will be conducted with the most aggressive brain tumors out there – IDH wild-type, methylation negative glioblastoma patients. This particular group of patients at this time only have radiation as the standard of care, with more than half of the patients surviving for less than 12 months after diagnosis. The Phase 2 trial will consist initially of 40 patients randomized into two different doses (20 @ 1,200 mg/day and 20 @ 960 mg/day) to determine an optimal dose. Once the Company determines the optimal dose, it will then add an additional 14 patients on the optimal dose allowing for the achievement of statistical significance with the end point being that of survival compared to historical controls. The Company expects the trial to be completed over a period of 18 to 24 months. “The initiation of patient dosing in our Phase 2 trial of Ropidoxuridine for the treatment of patients with glioblastoma is a significant milestone for both Shuttle Pharma and the thousands of patients with brain tumors who currently lack effective therapies,” commented Shuttle Pharma's Chairman and CEO, Anatoly Dritschilo, M.D. “The results of this trial will be important as Shuttle Pharma looks to leverage radiation sensitizers to increase cancer cure rates, prolong patient survival and improve quality of life for patients suffering from glioblastoma.” An estimated 800,000 patients in the US are treated with radiation therapy for their cancers yearly. According to the American Cancer Society and the American Society of Radiation Oncologists, about 50% are treated for curative purposes and the balance for therapeutic care. The market opportunity for radiation sensitizers lies with the 400,000 patients treated for curative purposes, with this number expected to grow by more than 22% over the next five years. More information about the Phase 2 study (NCT06359379) can be found at www.clinicaltrials.gov. About Shuttle Pharmaceuticals Founded in 2012 by faculty members of the Georgetown University Medical Center, Shuttle Pharma is a discovery and development stage specialty pharmaceutical company focused on improving the outcomes for cancer patients treated with radiation therapy (RT). Our mission is to improve the lives of cancer patients by developing therapies that are designed to maximize the effectiveness of RT while limiting the side effects of radiation in cancer treatment. Although RT is a proven modality for treating cancers, by developing radiation sensitizers, we aim to increase cancer cure rates, prolong patient survival and improve quality of life when used as a primary treatment or in combination with surgery, chemotherapy and immunotherapy. For more information, please visit our website at www.shuttlepharma.com. Safe Harbor Statement Statements in this press release about future expectations, plans and prospects, as well as any other statements regarding matters that are not historical facts, may constitute “forward-looking statements.” These statements include, but are not limited to, statements concerning the development of our company. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “will,” “would” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including factors discussed in the “Risk Factors” section of Shuttle Pharma’s Annual Report on Form 10-K for the year ended December 31, 2023, as amended, filed with the SEC on September 4, 2024, as well other SEC filings. Any forward-looking statements contained in this press release speak only as of the date hereof and, except as required by federal securities laws, Shuttle Pharmaceuticals specifically disclaims any obligation to update any forward-looking statement, whether as a result of new information, future events or otherwise. Shuttle PharmaceuticalsAnatoly Dritschilo, M.D., CEO240-403-4212info@shuttlepharma.com Investor ContactsLytham Partners, LLCRobert Blum602-889-9700shph@lythampartners.com

Phase 2Radiation TherapyOrphan Drug

100 Deals associated with Ropidoxuridine

External Link

KEGG	Wiki	ATC	Drug Bank
D08992	-	-	DB06485

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Glioblastoma, IDH-Wildtype	Phase 2	US	Shuttle Pharmaceuticals, Inc.	02 Sep 2024
Astrocytoma	Phase 2	-	Supergen Bioenergy Hub	-
Glioblastoma	IND Application	US	Shuttle Pharmaceuticals Holdings, Inc.	11 Dec 2023
Astrocytoma	Preclinical	-	Yale University	-
Astrocytoma	Preclinical	-	Central State University Of New York Inc	-

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02993146 (CTgov)	Phase 1	Malignant Solid Neoplasm \| Hematologic Neoplasms \| Brain metastases	11	ropidoxuridine (Dose Level 1A)	cfahalsinz(zfpvmnqiez) = sqsjlkiakp kehscjnrwj (wdutwrigyx, xdptdgrhzl - akbkytldje) View more	-	20 Feb 2024
NCT02993146 (CTgov)	Phase 1		11	ropidoxuridine (Dose Level 1B)	cfahalsinz(zfpvmnqiez) = knajjgtpkt kehscjnrwj (wdutwrigyx, rtaqjviavq - ieazzfrxuh) View more	-	20 Feb 2024
NCT04406857 (CTgov)	Phase 1	Rectal Adenocarcinoma \| Locally Advanced Rectal Carcinoma	1	Radiation Therapy+Ropidoxuridine+Capecitabine	kkqazorenq(mxbwddoemp) = ozucaijpns ivgfjpnrtl (ssqtnbpppz, cjidmmhsfm - niecdexixx) View more	-	05 Oct 2023
NCT02381561 (Pubmed \| Clin Cancer Res) Manual	Phase 1	Gastrointestinal Neoplasms	19	Radiotherapy+Ropidoxuridine	(ccohwlndsy) = zaasgocdzc qyvquztzrr (svykuquzqn ) View more	Positive	15 Oct 2019

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis