- |||||||||| Zarnestra (tipifarnib) / Kura Oncology
Enrollment change, Trial completion date, Trial termination, Trial primary completion date: Tipifarnib in Subjects With Myelodysplastic Syndromes (clinicaltrials.gov) - Feb 5, 2020
P2, N=16, Terminated,
Tipifarnib is currently being evaluated in HRAS mutant tumors, providing a potential opportunity to further test this combination. N=58 --> 16 | Trial completion date: Jun 2019 --> Jan 2020 | Recruiting --> Terminated | Trial primary completion date: Dec 2018 --> Dec 2019; Lack of efficacy
- |||||||||| simvastatin / Generic mfg., Flagyl (metronidazole) / SLA
Journal: Bioactivity of Farnesyltransferase Inhibitors Against Entamoeba histolytica and Schistosoma mansoni. (Pubmed Central) - Jan 28, 2020
Also, of a number of statins tested, simvastatin exhibited moderate anti-amebic activity which, when combined with lonafarnib, resulted in slight synergism. Even in the absence of a definitive molecular target, identification of potent anti-parasitic tipifarnib analogs encourages further exploration while the synergistic combination of metronidazole and lonafarnib offers a promising treatment strategy for amebiasis.
- |||||||||| paclitaxel / Generic mfg.
Biomarker, Preclinical, Journal, PARP Biomarker: MicroRNAs as possible indicators of drug sensitivity in breast cancer cell lines. (Pubmed Central) - Jan 15, 2020
Drug resistance was associated with hsa-miR-182-5p for Veliparib and hsa-miR-629-5p for Tipifarnib...By doing so hsa-miR-187-5p was linked to the cell cycle G2-M checkpoint in line with this checkpoint being the target of taxanes. In conclusion, our study shows that miRNAs could potentially serve as biomarkers for intrinsic drug resistance and that pathway analyses can provide additional information in this context.
- |||||||||| Zarnestra (tipifarnib) / Kura Oncology
Trial completion: Tipifarnib in Treating Patients With Relapsed or Refractory Lymphoma (clinicaltrials.gov) - Nov 29, 2019
P2, N=93, Completed,
In conclusion, our study shows that miRNAs could potentially serve as biomarkers for intrinsic drug resistance and that pathway analyses can provide additional information in this context. Active, not recruiting --> Completed
- |||||||||| Zarnestra (tipifarnib) / Kura Oncology
Journal: Tipifarnib Targets HRAS-Mutant Cancers. (Pubmed Central) - Nov 8, 2019
Tipifarnib may be effective in treating HRAS-mutant head and neck squamous cell carcinoma. In a phase II trial, the drug elicited responses in 10 of 18 patients with HRAS mutations at a variant allele frequency of at least 20%, and responders had a median progression-free survival of 8.3 months.
- |||||||||| Zarnestra (tipifarnib) / Kura Oncology
Tipifarnib Modulates Interferon (IFN)-γ-Inducible Genes in Acute Myeloid Leukemia (Hall B, Level 2 (Orange County Convention Center)) - Nov 7, 2019 - Abstract #ASH2019ASH_3902;
Conclusions Our study shows that an experimentally-derived IFN-γ responsiveness gene signature correlates with poor clinical outcomes in AML and suggests that tipifarnib might attenuate IFN-γ signaling, potentially affecting AML susceptibility to DNA damage induced by chemotherapeutic agents . Grant support: Qatar National Research Fund (#NPRP8-2297-3-494) and Kura Oncology, San Diego, CA, USA.
- |||||||||| Zarnestra (tipifarnib) / Kura Oncology
Enrollment change, Trial completion date, Trial primary completion date: Tipifarnib in Subjects With Chronic Myelomonocytic Leukemia, Other MDS/MPN, and Acute Myeloid Leukemia (clinicaltrials.gov) - Oct 16, 2019
P2, N=72, Recruiting,
Extended enrollment of AITL patients continues and an update on enrollment and outcomes will be provided at the time of the presentation. N=20 --> 72 | Trial completion date: Apr 2019 --> May 2022 | Trial primary completion date: Dec 2018 --> Apr 2021
- |||||||||| Zarnestra (tipifarnib) / Kura Oncology, fenoterol / Generic Mfg., Gracevit (sitafloxacin) / Daiichi Sankyo
Journal: High-throughput screening identified selective inhibitors of exosome biogenesis and secretion: A drug repurposing strategy for advanced cancer. (Pubmed Central) - Oct 10, 2019
The lead compounds tipifarnib, neticonazole, climbazole, ketoconazole, and triademenol were validated as potent inhibitors and sitafloxacin, forskolin, SB218795, fenoterol, nitrefazole and pentetrazol as activators of exosome biogenesis and/or secretion in PC cells. Our findings implicate the potential utility of drug-repurposing as novel adjunct therapeutic strategies in advanced cancer.
- |||||||||| Zarnestra (tipifarnib) / Kura Oncology
Journal: Tipifarnib inhibits HRAS-driven dedifferentiated thyroid cancers. (Pubmed Central) - Sep 28, 2019
Cell lines modified with these genetic lesions recapitulated tipifarnib resistance in vivo. This study demonstrates the feasibility of targeting Ras membrane association in cancers in vivo and predicts combination therapies that confer additional benefit.
- |||||||||| Zarnestra (tipifarnib) / Kura Oncology, Erbitux (cetuximab) / Eli Lilly, EMD Serono
Preliminary results from a phase 2 trial of tipifarnib in squamous cell carcinomas (SCCs) with HRAS mutations. (Board 134: Level 2 - Hall D) - Sep 18, 2019 - Abstract #AACRNCIEORTC2019AACR_NCI_EORTC_588;
P2
Conclusion Encouraging activity of tipifarnib was observed in HRAS mutant HNSCC. Based on these data, a pivotal study (AIM-HN and SEQ-HN Study, NCT03719690) evaluating the efficacy of this agent in HRAS mutant HNSCC (AIM-HN) and the impact of HRAS mutations on first line therapy of HNSCC (SEQ-HN) has been initiated.
- |||||||||| Zarnestra (tipifarnib) / Kura Oncology, Erbitux (cetuximab) / Eli Lilly, EMD Serono
Preliminary results from a phase 2 trial of tipifarnib in squamous cell carcinomas (SCCs) with HRAS mutations. (Level 3 - Ballroom AB Lobby) - Sep 18, 2019 - Abstract #AACRNCIEORTC2019AACR_NCI_EORTC_570;
P2
Conclusion Encouraging activity of tipifarnib was observed in HRAS mutant HNSCC. Based on these data, a pivotal study (AIM-HN and SEQ-HN Study, NCT03719690) evaluating the efficacy of this agent in HRAS mutant HNSCC (AIM-HN) and the impact of HRAS mutations on first line therapy of HNSCC (SEQ-HN) has been initiated.
- |||||||||| Zarnestra (tipifarnib) / Kura Oncology, Ibrance (palbociclib) / Pfizer
Preclinical, Journal: The efficacy of HRAS and CDK4/6 inhibitors in anaplastic thyroid cancer cell lines. (Pubmed Central) - Aug 23, 2019
Legal entity responsible for the study: The authors. This study suggests that TIP and PD, which are currently in clinical trials for other types of cancer, may play a relevant role in ATC treatment, depending on the specific tumour molecular profile.
- |||||||||| Avastin (bevacizumab) / Roche
Journal: A mixed treatment comparison of toxicity of gemcitabine combined with different targeted drugs in the treatment of advanced or metastatic pancreatic cancer. (Pubmed Central) - Jun 20, 2019
Moreover, the cluster analyses results revealed that Gemcitabine + Axitinib combinations and Gemcitabine + Sorafenib combinations showed lower incidence rates of hematotoxicity, while Gemcitabine + Axitinib combinations showed lower incidence rates of non-hematotoxicity. Collectively, the data provided strong evidence of Gemcitabine + Axitinib combinations showing lower incidence rates of non-hematotoxicity, and Gemcitabine + Axitinib and Gemcitabine + Sorafenib combinations may have lower incidence rates of hematotoxicity in the treatment of advanced/metastatic PC.
- |||||||||| GSK690693 / GSK, Zarnestra (tipifarnib) / Kura Oncology, vistusertib (AZD2014) / AstraZeneca
Journal: Comparative toxicity evaluation of targeted anticancer therapeutics in embryonic zebrafish and sea urchin models. (Pubmed Central) - Jun 15, 2019
AZD2014 also caused the least prominent effects on sea urchin embryo development compared to other inhibitors. Significant toxicity of AZD2014 in human cancer cells, its capacity to sensitize resistant cancers, lower antiproliferative activity against human normal cell lines and fast proliferating embryonic cells could make this agent a promising candidate for anticancer therapy.
- |||||||||| Zarnestra (tipifarnib) / Kura Oncology
Trial completion date, Trial primary completion date, Metastases: Study of Tipifarnib in Patients With Previously-Treated, Advanced, HRAS Mutant Urothelial Carcinoma (clinicaltrials.gov) - May 20, 2019
P2, N=18, Recruiting,
Significant toxicity of AZD2014 in human cancer cells, its capacity to sensitize resistant cancers, lower antiproliferative activity against human normal cell lines and fast proliferating embryonic cells could make this agent a promising candidate for anticancer therapy. Trial completion date: Mar 2018 --> Mar 2020 | Trial primary completion date: Sep 2017 --> Dec 2019
- |||||||||| Zarnestra (tipifarnib) / Kura Oncology
Enrollment change, Trial completion date, Trial primary completion date, Metastases: KO-TIP-001: Phase II Study of Tipifarnib in Squamous Head and Neck Cancer With HRAS Mutations (clinicaltrials.gov) - May 9, 2019
P2, N=75, Recruiting,
Trial completion date: Mar 2018 --> Mar 2020 | Trial primary completion date: Sep 2017 --> Dec 2019 N=36 --> 75 | Trial completion date: Aug 2019 --> Oct 2020 | Trial primary completion date: Mar 2019 --> Mar 2020
- |||||||||| Zarnestra (tipifarnib) / Kura Oncology, Nexavar (sorafenib) / Bayer, Amgen
P1 data, Journal: Phase I study of sorafenib and tipifarnib for recurrent glioblastoma: NABTC 05-02. (Pubmed Central) - Feb 1, 2019
The DLTs included diarrhea, lipase elevation, hypophosphatemia, and arthralgia. The combination of sorafenib and tipifarnib has excessive toxicities and full single agent dosages could not be achieved in combination.
- |||||||||| Biomarker, Enrollment change, BRCA Biomarker, PARP Biomarker, Metastases: Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders (The Pediatric MATCH Screening Trial) (clinicaltrials.gov) - Nov 5, 2018
P2, N=1000, Recruiting,
The combination of sorafenib and tipifarnib has excessive toxicities and full single agent dosages could not be achieved in combination. N=1500 --> 1000
- |||||||||| Zarnestra (tipifarnib) / Kura Oncology
Trial completion date, Trial primary completion date: Tipifarnib in Subjects With Myelodysplastic Syndromes (clinicaltrials.gov) - Aug 23, 2018
P2, N=58, Recruiting,
Trial completion date: Aug 2018 --> Aug 2019 | Trial primary completion date: Mar 2018 --> Mar 2019 Trial completion date: Jun 2018 --> Jun 2019 | Trial primary completion date: Feb 2018 --> Dec 2018
- |||||||||| Zarnestra (tipifarnib) / Kura Oncology
Enrollment open, Metastases: Tipifarnib in Advanced Squamous NSCLC With Oncogen HRAS MutAtionS (clinicaltrials.gov) - Aug 10, 2018
P2, N=18, Recruiting,
Trial completion date: Jun 2018 --> Jun 2019 | Trial primary completion date: Feb 2018 --> Dec 2018 Not yet recruiting --> Recruiting
- |||||||||| Biomarker, Trial completion date, Trial primary completion date, BRCA Biomarker, PARP Biomarker, Metastases: Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders (The Pediatric MATCH Screening Trial) (clinicaltrials.gov) - Apr 12, 2018
P2, N=1500, Recruiting,
Active, not recruiting --> Completed Trial completion date: Dec 2021 --> Sep 2027 | Trial primary completion date: Dec 2021 --> Sep 2027
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