Phase I study of vorinostat, a histone deacetylase (HDAC) inhibitor, in combination with carboplatin (Cb) and paclitaxel (P) for patients with advanced solid malignancies (NCI #6922)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 2077-2077 ◽  
Author(s):  
S. Ramalingam ◽  
R. A. Parise ◽  
M. J. Egorin ◽  
A. Argiris ◽  
R. Stoller ◽  
...  
Keyword(s):  
Phase I ◽  
Phase I Study ◽  
Single Agent ◽  
Plasma Concentrations ◽  
Human Carcinoma ◽  
Carcinoma Cell Lines ◽  
Solid Malignancies ◽  
Human Carcinoma Cell ◽  
Oxobutanoic Acid ◽  
Recommended Phase Ii Dose

2077 Background: Vorinostat (SAHA) induces differentiation & growth arrest in a variety of human carcinoma cell lines by inhibiting HDAC. It also enhances the efficacy of chemotherapy. We are conducting a phase I study to evaluate the combination of vorinostat, Cb & P for patients with advanced solid malignancies. Methods: Patients with advanced solid malignancies who were candidates for combination therapy with Cb & P were eligible. Vorinostat was given orally on d 1–14 of each 21-d-cycle, except in cycle 1 when begun on d -4 to facilitate PK studies. Cb & P were given on d 1 of each cycle. Plasma concentrations of vorinostat, & its 2 major metabolites were quantitated with a novel LC-MS/MS assay. Results: Dose level 4 has been determined as the recommended phase II dose (RP2D) for the combination, since the RP2D of single agent vorinostat is 400 mg on this schedule. Observed toxicities included nausea, vomiting, neutropenia & thrombocytopenia, none of which were dose-limiting. Of 9 patients evaluable for response, 4 had PR (1 head & neck cancer, 3 non-small cell lung cancer), & 2 had stable disease. Vorinostat was rapidly absorbed & AUC increased with dose. Vorinostat PK parameters included Tmax 0.5–2 h, t1/2 1.6 ± 0.5 h, & CL/F 5.8 ± 1.7 l/min. Cb & P did not alter vorinostat PK. 4-Anilino-4-oxobutanoic acid was the major, & long-lived, vorinostat metabolite, with Cmax 1.5–7 fold > vorinostat Cmax & t ½ ∼6h. Vorinostat glucuronide Cmax was 1–5 fold > vorinostat Cmax & glucuronide t ½ ∼2h. The RP2D cohort is being expanded to 12 patients to obtain additional clinical & PK data. Conclusions: Vorinostat can be safely administered in combination with Cb & P at their recommended doses. Vorinostat PK are not altered by Cb & P. Promising anti-cancer activity has been noted in patients with advanced NSCLC. Support: U01CA099168–01, U01CA62505, NIH/NCCR/GCRC grant 5M01RR 00056. [Table: see text] No significant financial relationships to disclose.

Phase I study of midostaurin and azacitidine in relapsed and elderly AML.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 7058-7058 ◽  
Author(s):  
Brenda W. Cooper ◽  
Tamila L. Kindwall-Keller ◽  
Hillard M. Lazarus ◽  
Mehdi Hamadani ◽  
William W. Tse ◽  
...  
Keyword(s):  
Phase I ◽  
Phase I Study ◽  
Single Agent ◽  
Plasma Concentrations ◽  
Leukemic Cells ◽  
Elderly Aml ◽  
Grade 3 ◽  
Normal Cytogenetics ◽  
Expansion Cohort ◽  
Ecog Ps

7058 Background: The Fms-like tyrosine kinase 3 (FLT3) receptor is expressed in 80% of AML and activating mutations are associated with an adverse prognosis. Midostaurin (mdn), an orally available agent, has been shown to inhibit FLT3 receptor signaling and induces cell cycle arrest and apoptosis of leukemic cells expressing both mutant and wild type FLT3 receptors. Preliminary data has shown modest single agent activity as well as safety and tolerablility of mdn in combination with standard induction chemotherapy. Methods: We conducted a phase I study of azacitidine (75 mg/m2 iv X 7days) with escalating doses of oral mdn (25 mg bid, 50 mg bid, and 75 mg bid) days 8-21 of a 28 day cycle in untreated elderly and relapsed AML. The protocol was IRB approved at participating institutions and all patients gave written informed consent. Dose limiting toxicities (DLTs) were defined as > grade 3 non-heme toxicity during cycle 1 excluding grade 3 hepatotoxicity < 7 days, grade 3/4 stomatitis or diarrhea that resolved by day 28, infections, and electrolyte abnormalities of any grade. Pharmacokinetics (pK) were obtained on day 8,15, and 21 before mdn dosing. Results: 17 pts (11 females and 6 males) ages 57-83 ( median 73) were enrolled of whom 5 patients had prior intensive treatment for AML. All pts were FLT3 negative; 5 had normal cytogenetics and 12 had high risk cytogenetics. ECOG PS: 0 (4pts), 1 (11pts), 2 (2pts). No DLT were observed during escalation or in the expansion cohort of 75 mg bid. Responses were evaluable in 14/17 pts and included 2 CR, 1 PR, and 2 HI (clearing of peripheral blasts, platelet tx independence). Median survival from enrollment was 3.5 months (range 1-12 months). 4 pts remain on treatment (2- 9+ cycles). 3 pts died within 60 days (2 PD, 1 treatment-related). Non-infectious, non hematologic SAE’s are listed on the table below. Plasma concentrations of mdn accumulated in the first week of treatment and declined thereafter despite continued dosing. Conclusions: The combination of azacitidine and midostaurin in safe and tolerable in elderly AML and should be further studied in FLT3 positive leukemia. Clinical trial information: NCT01093573. [Table: see text]

A multicenter phase I study of intravenous administration of reolysin in combination with irinotecan/fluorouracil/leucovorin (FOLFIRI) in patients (pts) with oxaliplatin-refractory/intolerant KRAS-mutant metastatic colorectal cancer (mCRC).

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 450-450 ◽  
Author(s):  
Allyson J. Ocean ◽  
Tanios S. Bekaii-Saab ◽  
Imran Chaudhary ◽  
Romae Palmer ◽  
Paul J. Christos ◽  
...  
Keyword(s):  
Phase I ◽  
Phase I Study ◽  
Single Agent ◽  
Dose Escalation Study ◽  
Significant Toxicity ◽  
Secondary Endpoints ◽  
Adequate Organ Function ◽  
Grade 3 ◽  
Recommended Phase Ii Dose ◽  
Ecog Ps

450 Background: Reolysin (reovirus serotype 3) contains a naturally occurring, ubiquitous, non-enveloped human dearing strain reovirus. Reovirus replicates in KRAS-mutant cells resulting in cell lysis. In phase I evaluation, CRC pts received single agent Reolysin with tumor stabilization and CEA response without significant toxicity. Reolysin and irinotecan (IRI) are synergistic in KRAS-mutant preclinical CRC models, providing rationale for this phase I study. Methods: This was a phase I dose escalation study of FOLFIRI + Reolysin. Eligible pts were >18 yrs with histologically confirmed KRAS-mutant mCRC, measurable disease, ECOG PS 0-1, <3 metastatic regimens, and adequate organ function. Standard FOLFIRI was administered with escalating Reolysin doses (range 1x1010 TCID50 to 3x1010 TCID50) in cohorts of 3-6 pts. Reolysin was given IV over 1 hr days 1-5 every 28d (1 cycle). Primary objectives were dose-limiting toxicity (DLT) to determine MTD and pharmacokinetics. Secondary endpoints were antitumor activity, response rate, progression-free and overall survival (PFS and OS). Results: 21 pts enrolled; median age 62 (range 39-77); 5 M; 16 F; FOLFIRI-naïve: 9/21 pts. 2 pts had DLTs in cycle 1 at the highest dose of 180 mg/m2 of IRI. Common (>10%) grade 3-4 toxicity include: neutropenia (n=11), anemia (n=4), and thrombocytopenia (n=3). One patient died of acute renal failure. The DLT is neutropenia. The recommended phase II dose is IRI 150 mg/m2 and Reolysin at 3x1010 TCID50 on days 1-5, q 28 days. 18 pts evaluable for response: PR (1pt; 5%), SD (9 pts; 50%), PD (8pts; 44%). 3 pts taken off study before evaluation. Median PFS: FOLFIRI-naïve pts = 7.4 mo. (95% CI = 1.9 mo., 12.9 mo.); Median PFS FOLFIRI non-naïve pts was not reached; overall median PFS = 7.4 mo. (95% CI = 0.6 mo., 14.1 mo.) Conclusions: The combination of Reolysin and FOLFIRI in pts with KRAS-mutant mCRC was safe, well tolerated and resulted in disease control in the majority of pts, including pts who previously progressed on IRI. We are encouraged by this activity and safety profile, and are planning additional studies. Clinical trial information: NCT01274624.

A phase I study of the safety and pharmacodynamic effects of everolimus in combination with lenalidomide in patients with advanced solid malignancies.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 2576-2576 ◽  
Author(s):  
Taofeek Kunle Owonikoko ◽  
R Donald Harvey ◽  
John S Kauh ◽  
Colleen Margaret Lewis ◽  
Mohammed S Hossain ◽  
...  
Keyword(s):  
T Cell ◽  
Phase I ◽  
Phase I Study ◽  
Mtor Inhibitor ◽  
Single Agent ◽  
Cell Subset ◽  
T Cell Subsets ◽  
Cytotoxic T Cell ◽  
Multiparameter Flow Cytometry ◽  
Solid Malignancies

2576 Background: Everolimus (E), an mTOR inhibitor, and Lenalidomide (L) are both potent anti cancer agents with immunomodulatory effects. Preclinical evidence of enhanced cytotoxicity of the combination of an mTOR inhibitor and lenalidomide provided the rationale for this phase I study. Methods: Patients with advanced solid malignancies, ECOG performance status (PS) 0-2 and adequate organ function were eligible. Using standard 3+3 dose escalation schema, patients were treated in cohorts of three with increasing doses of E (5mg, 10mg) and L (10, 15, 20, 25mg) on day 1-28 of a 28-day cycle. Treatment cycles were repeated until disease progression by RECIST criteria or intolerable toxicity. Pharmacodynamic (PD) effects of treatment on circulating B and T lymphocytes subsets were assessed by multiparameter flow cytometry at baseline and after 2 cycles. Results: We enrolled 21 patients (thyroid-5, salivary gland-5, colon-4, sarcoma-2, and others-5); median age-58 (29-74); male-13; ECOG PS of 0, 1, 2 (3/17/1). Salient grade 3/4 toxicities included rash (67%), anemia (19%) and vomiting (5%) without dose limiting toxicities. The median number of completed cycles was 3 (1 - ≥15) and best response in 14 of 18 evaluable patients was stable disease (range 2- ≥14 months); median PFS was 116 days (14- ≥498). The RP2D of E and L was defined as 10mg and 25mg once daily, respectively. PD endpoint analysis after 2 cycles of treatment showed a significant increase in activated cytotoxic T cell subset (CD8+ICOS1+) in patients with salivary or thyroid cancers compared to other tumor types (+2051.0 vs. +394 vs. -1687.4 respectively; p=0.0303) and a trend for an increase in patients with non-progressing tumors (+661.7 vs. -384.1; p=0.0988). Other significant correlations were: Changes in total B-cells (CD3-CD19+) with PFS; NK cells with age (p=0.0211) and activated T cells (CD3+CD69+; CD3+CD62L-; p=0.01) with gender. Conclusions: The combination of E and L is well tolerated at the recommended single agent doses and showed promising efficacy in neuroendocrine and salivary adenoidcystic carcinoma. Modulation of activated T cell subsets (CD8+ICOS1+) correlates with efficacy of these agents.

Phase I study of everolimus (E, RAD001) and ganitumab (G, AMG 479) in patients (pts) with advanced solid tumors.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 2529-2529 ◽  
Author(s):  
Shadia Ibrahim Jalal ◽  
Robert Matthew Strother ◽  
George Sandusky ◽  
Nagendra K Prasad ◽  
William Berry ◽  
...  
Keyword(s):  
Phase I ◽  
Clinical Benefit ◽  
Phase I Study ◽  
Single Agent ◽  
Mtor Inhibitors ◽  
Efficacy Analysis ◽  
G 12 ◽  
Recommended Phase Ii Dose ◽  
Ecog Ps ◽  
Tumor Biopsies

2529 Background: Synergism between IGF and mTOR inhibitors has been documented preclinically. We conducted a phase I study to determine the safety, recommended phase II dose (RP2D), pharmacokinetics (PK), pharmacodynamics (PD), and antitumor efficacy of E with G. Methods: Eligible pts had good organ function, ECOG PS 0-1. The study had a standard “3+3” design, using E 5 or 10 mg orally daily (QD), and G 12 mg/kg IV every 2 wks (Q2W) in 28 day cycles (C); an expansion cohort was added at MTD for further efficacy analysis. E was given as single agent during C1D1-7 with PKs on C1D1 and D7, and continuously after C1D16. G was started on C1D15 with single agent PK. PKs for both drugs at steady state were performed on C3D1. PDs (blood and serial tumor biopsies) for IGF and PI3K/Akt/mTOR pathways were performed at baseline, C1D7, C3D1 and time of progression. Results: 20 ptswere enrolled to date, M/F: 8/12, median age 55 yrs (24-70); PS: 0/1= 13/7. The table summarizes dose levels and DLTs. The most common toxicities were fatigue (5), diarrhea, mucositis, dysgeusia, anemia and thrombocytopenia (4 each), and rigors (3). Grade (Gr) 3 toxicities were: mucositis (3), anemia (2), thrombocytopenia (2), and diarrhea (1). Pts received a median of 3 cycles (0-9). One pt discontinued study on C1D9 due to intracerebral bleed and 1 pt withdrew consent on C1D15. Among 18 evaluable pts, none responded and 9 pts (50%) had SD with a median duration of 20 wks (range 11-35). Prolonged clinical benefit (SD ≥ 20 wks) was noted in refractory fibrolamellar HCC, neuroendocrine, GIST and urachal cancers. PKs showed no significant interaction between E and G. Baseline IGF-1R and PTEN expression, and IGF1 levels did not affect clinical benefit. pS6 downregulation and pAkt upregulation in paired tumor biopsies occurred in all (7/7) or most (6/7) samples evaluated, and did not correlate with efficacy. IGF1 and IGFBP3 levels increased on-treatment in 80-90% of pts. Conclusions: E+G is safe and the RP2D is E 10 mg QD + G 12 mg/kg Q2W. While on target pS6 reduction occured, the IGF1-R inhibition did not affect pAkt upregulation from mTOR blockade. Clinical trial information: NCT01122199. [Table: see text]

Phase I study of temsirolimus (CCI-779), carboplatin, and paclitaxel in patients (pts) with advanced solid tumors: NCIC CTG IND 179

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 3558-3558
Author(s):  
A. M. Oza ◽  
C. Kollmannsberger ◽  
H. Hirte ◽  
S. Welch ◽  
L. Siu ◽  
...  
Keyword(s):  
Phase I ◽  
Dose Level ◽  
Phase Ii ◽  
Phase I Study ◽  
Solid Malignancies ◽  
Recommended Phase Ii Dose ◽  
Dose Levels ◽  
Further Development ◽  
Dose Limiting Toxicity

3558 Background: Temsirolimus (T) has encouraging activity in many malignancies, including endometrial cancer and a combination with carboplatin and paclitaxel would logical regimen for further development. This trial was designed to assess the safety and tolerability of this combination and expand experience at the recommended dose in pts with endometrial and ovarian cancers. Methods: A 3+3 dose escalation Phase I study has been conducted in pts with advanced solid malignancies suitable for carboplatin and paclitaxel chemotherapy who had not received more than 2 prior lines of chemotherapy. To date, 31 eligible pts with a median age of 59 have been treated and 27 are evaluable for toxicity. Pts were entered in 6 dose levels, with the first two levels administering T on Days 8 and 15 and the next 4 levels switching to a D1, 8 administration. Eighteen had received prior chemotherapy and 15 prior radiation. Results: Day 8, 15 administration of T was not feasible due to myelosuppression on day 15. The combination of carboplatin and paclitaxel on day 1 with T on D1 and 8 has been well tolerated, and patients have received a median of 5 cycles of therapy. At dose level 6 (T 25 mg D1 and 8, paclitaxel 175 mg/m2 D1, carboplatin AUC 6 D1) dose limiting toxicity (DLT) was seen in one of 6 pts treated to date (Gr 4 thrombocytopenia) and a second pt had a possible DLT ( Gr 3 fatigue in presence of baseline fatigue). This dose level is being expanded in 4 endometrial and ovarian cancer pts. The regimen is active: of the 26 patients with follow-up data, there have been 10 with partial response (38.5%; med. duration 7.1 mo [1.0–12.7]) and 12 with stable disease (46%; med. duration 6.9 mo [1.3- 7.8]). One patient had progressive disease and three were inevaluable. Conclusions: The results indicate this combination is well tolerated and requires additional assessment in a Phase II setting. The recommended Phase II dose will be dose level 6 provided no further DLTs are observed in the additional 4 patients entered. [Table: see text] No significant financial relationships to disclose.

Synthesis and Antitumor Activity Evaluation of New Phenanthrene-Based Tylophorine Derivatives

2019 ◽  
Vol 16 (6) ◽  
pp. 462-467
Author(s):  
Songtao Li ◽  
Hongling Zhao ◽  
Zhifeng Yin ◽  
Shuhua Deng ◽  
Yang Gao ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Cell Lines ◽  
Antitumor Activities ◽  
Human Carcinoma ◽  
Carcinoma Cell Lines ◽  
Structure Activity ◽  
Human Carcinoma Cell ◽  
Ic50 Values ◽  
Relationship Of

A series of new phenanthrene-based tylophorine derivatives (PBTs) were synthesized in good yield and their structures were characterized by 1H-NMR spectroscopy and ESI MS. In vitro antitumor activity of these compounds against five human carcinoma cell lines, including HCT116 (colorectal), BGC-823 (gastric), HepG-2 (hepatic), Hela (cervical) and H460 (lung) cells, was evaluated by MTT assay. Among these PBTs, compound 6b showed the highest antitumor activities against HCT116 and HepG-2 cell lines with IC50 values of 6.1 and 6.4 μM, respectively, which were comparable to that of adriamycin hydrochloride. The structure-activity relationship of these compounds was also discussed based on the results of their antitumor activity.

Synthesis and Anti-Tumor Activity Evaluation of Novel 7-Fluoro-4-(1- Piperazinyl) Quinolines

2019 ◽  
Vol 16 (6) ◽  
pp. 663-669
Author(s):  
Dan Liu ◽  
Aiqi Xue ◽  
Zhixin Liu ◽  
Yi Zhang ◽  
Penghui Peng ◽  
...  
Keyword(s):  
Spectral Analysis ◽  
Cancer Therapy ◽  
Carcinoma Cell ◽  
A549 Cells ◽  
Quinoline Derivatives ◽  
Human Carcinoma ◽  
Carcinoma Cell Lines ◽  
Human Carcinoma Cell ◽  
Anti Tumor Activity

Background: Three series of new 7-fluoro-4-(1-piperazinyl) quinolines (I1~I6, II1~II2 and IV1~IV4) were synthesized. Their anti-tumor activity was evaluated in vitro against three human carcinoma cell lines, namely SGC-7901 cells, BEL-7402 cells and A549 cells expressing high levels of EGFR by Methyl Thiazolyl Terazolium (MTT) assay. Methods: Three series of quinoline derivatives were synthesized, characterized and evaluated for their in vitro anti-tumor activities. Results and Discussion: Structures of the newly synthesized compounds were confirmed by spectral analysis. The preliminary bioassay indicated that compounds I1, I10 and II1 exhibited better anti-tumor activity than the rest of the target compounds and gefitinib against A549 cell based assay, which demonstrated that compounds I1, I10 and II1 are potential agents for cancer therapy. Results suggested that the substitutes on piperazinyl influenced anti-tumor activities remarkably. Conclusion: These results are useful for discovering more potent novel anti-tumor compounds and further studies are ongoing.

scholarly journals Crystallization, Luminescence and Cytocompatibility of Hexagonal Calcium Doped Terbium Phosphate Hydrate Nanoparticles

Nanomaterials ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 322
Author(s):  
Jaime Gómez-Morales ◽  
Raquel Fernández-Penas ◽  
Ismael Romero-Castillo ◽  
Cristóbal Verdugo-Escamilla ◽  
Duane Choquesillo-Lazarte ◽  
...  
Keyword(s):  
Inductively Coupled Plasma ◽  
Doping Concentration ◽  
Hydration Number ◽  
Maturation Time ◽  
Human Carcinoma ◽  
Inductively Coupled ◽  
Carcinoma Cell Lines ◽  
Carbonate Solutions ◽  
Human Carcinoma Cell ◽  
Calcium Doped

Luminescent lanthanide-containing biocompatible nanosystems represent promising candidates as nanoplatforms for bioimaging applications. Herein, citrate-functionalized calcium-doped terbium phosphate hydrate nanophosphors of the rhabdophane type were prepared at different synthesis times and different Ca2+/Tb3+ ratios by a bioinspired crystallization method consisting of thermal decomplexing of Ca2+/Tb3+/citrate/phosphate/carbonate solutions. Nanoparticles were characterized by XRD, TEM, SEM, HR-TEM, FTIR, Raman, Thermogravimetry, inductively coupled plasma spectroscopy, thermoanalysis, dynamic light scattering, electrophoretic mobility, and fluorescence spectroscopy. They displayed ill-defined isometric morphologies with sizes ≤50 nm, hydration number n ~ 0.9, tailored Ca2+ content (0.42–8.11 wt%), and long luminescent lifetimes (800–2600 µs). Their relative luminescence intensities in solid state are neither affected by Ca2+, citrate content, nor by maturation time for Ca2+ doping concentration in solution below 0.07 M Ca2+. Only at this doping concentration does the maturation time strongly affect this property, decreasing it. In aqueous suspensions, neither pH nor ionic strength nor temperature affect their luminescence properties. All the nanoparticles displayed high cytocompatibility on two human carcinoma cell lines and cell viability correlated positively with the amount of doping Ca2+. Thus, these nanocrystals represent promising new luminescent nanoprobes for potential biomedical applications and, if coupled with targeting and therapeutic moieties, they could be effective tools for theranostics.

scholarly journals EPCT-19. A PHASE I STUDY OF RIBOCICLIB AND EVEROLIMUS FOLLOWING RADIATION THERAPY IN CHILDREN WITH NEWLY DIAGNOSED NON-BIOPSIED DIFFUSE PONTINE GLIOMAS (DIPG) AND RB+ BIOPSIED DIPG AND HIGH GRADE GLIOMAS (HGG)

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii307-iii307
Author(s):  
Mariko DeWire ◽  
James Leach ◽  
Christine Fuller ◽  
Peter de Blank ◽  
Trent Hummel ◽  
...  
Keyword(s):  
Phase I ◽  
Phase I Study ◽  
Single Agent ◽  
Maximum Tolerated Dose ◽  
Pharmacokinetic Studies ◽  
High Grade ◽  
Newly Diagnosed ◽  
High Grade Gliomas ◽  
Grade 3 ◽  
Expansion Cohort

Abstract Genomic aberrations in the cell cycle and mTOR pathways have been reported in diffuse pontine gliomas (DIPG) and high-grade gliomas (HGG). Dual inhibition of CDK4/6 (ribociclib) and mTOR (everolimus) has strong biologic rationale, non-overlapping single-agent toxicities, and adult clinical experience. The maximum tolerated dose (MTD) and/or recommended phase two dose (RP2D) of ribociclib and everolimus administered during maintenance therapy following radiotherapy was determined in the phase I study as a rolling 6 design. Ribociclib and everolimus were administered once daily for 21 days and 28 days, respectively starting two-four weeks post completion of radiotherapy. All HGG patients and any DIPG patient who had undergone biopsy were screened for RB protein by immunohistochemistry. Eighteen eligible patients enrolled (median age 8 years; range: 2–18). Six patients enrolled at dose levels 1,2, and 3 without dose limiting toxicities (DLT). Currently, five patients are enrolled at dose level 3 expansion cohort. The median number of cycles are 4.5 (range: 1–20+). Among the expansion cohort, one dose limiting toxicity included a grade 3 infection and one patient required a dose reduction in course 3 due to grade 3 ALT and grade 4 hypokalemia. The most common grade 3/4 adverse events included neutropenia. Preliminary pharmacokinetic studies on 12 patients suggest an impact of ribociclib on everolimus pharmacokinetics. The MTD/RP2D of ribociclib and everolimus following radiotherapy in newly diagnosed DIPG and HGG is anticipated to be 170 mg/m2/day x 21 days and 1.5 mg/ m2/day every 28 days which is equivalent to the adult RP2D.

Sign in / Sign up

Export Citation Format

Share Document