Phase I study of CNTO 95, a fully human monoclonal antibody to αv integrins, docetaxel, and prednisone in hormone refractory prostate cancer patients (HRPCP)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15595-15595
Author(s):  
F. M. Chu ◽  
J. Picus ◽  
M. Mata ◽  
C. Kopacynski ◽  
B. Foster ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Standard Dose ◽  
Human Monoclonal Antibody ◽  
Oral Prednisone ◽  
Standard Of Care ◽  
Primary Objective ◽  
Hormone Refractory ◽  
Grade 3 ◽  
Cancer Tissues ◽  
Group 1

15595 Background: CNTO 95 has demonstrated preclinical antitumor activity through binding to multiple av integrins, resulting in growth inhibition indirectly through anti-angiogenic effects as well as directly by inhibiting tumor cell proliferation. The target, av integrins, has been demonstrated by immunohistochemistry in a large proportion of human prostate cancer tissues. Docetaxel and prednisone have become a standard of care for HRPCP. The primary objective of this study was to evaluate the safety of combining CNTO 95 with this standard. Methods: Patients received day 1 infusions of 75 mg/m2 docetaxel together with twice daily oral prednisone in every 3 week cycles, with weekly infusions of either 5 or 10 mg/kg of CNTO 95 for 7 weeks beginning with the second docetaxel cycle, then CNTO 95 on the days of docetaxel thereafter. Patients were monitored for safety and PSA. Radiologic tumor assessments were performed at least every 4 cycles. Results: Six patients have received docetaxel and prednisone with CNTO 95 at either 5 mg/kg (n=3) or 10 mg/kg (n=3). In the 5 mg/kg group, 1 received 8 cycles then withdrew consent because of fluctuating PSA levels; 1 received 9 cycles then had soft tissue disease progression; and 1 has completed 9 cycles and remains on study treatment. In the 10 mg/kg group, all patients remain on study and have received 7, 6, and 6 cycles of treatment, respectively. There were no unexpected toxicities and only one Grade 3 toxicity (febrile neutropenia) attributed to docetaxel. A 50% decline in PSA occurred in 1 patient treated in the 10 mg/kg group. Conclusions: The combination of standard dose docetaxel and prednisone with 10 mg/kg of CNTO 95 was well tolerated and 3 new patients are planned to be treated with these doses on this study. Further study is warranted. [Table: see text]

A phase I study of ABT-751 in combination with docetaxel in patients with metastatic hormone-refractory prostate cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4651-4651
Author(s):  
J. E. Michels ◽  
S. Ellard ◽  
L. Le ◽  
N. Murray ◽  
E. Guns ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Febrile Neutropenia ◽  
Phase Ii ◽  
Oral Prednisone ◽  
Single Agent ◽  
Hormone Refractory Prostate Cancer ◽  
Best Response ◽  
Hormone Refractory ◽  
Grade 3 ◽  
Dose Levels

4651 Background: ABT-751 (A) is a novel oral sulfonamide anti-microtubule agent with broad-spectrum preclinical activity including paclitaxel-resistant tumors and additive effect with docetaxel (D). Dose-limiting toxicities (DLTs) with ABT-751 include peripheral neuropathy, ileus, and fatigue. The recommended phase II single-agent dose for a 21/28-day schedule is 200 mg/day. Methods: Patients (pts) with hormone-refractory prostate cancer (HRPC), ECOG performance status ≤ 2, and adequate organ function were eligible. D was administered intravenously on day 1 and A was administered orally once daily on days 1–14 of a 21-day cycle for a maximum of 10 cycles. Starting dose was 60 mg/m2 D and 100 mg A; escalated in 4 dose levels (DLs) to 75 mg/m2 D and 200 mg A. Pts received 10 mg oral prednisone daily. Plasma for PK analyses was obtained. Results: 18 pts have been enrolled (3 pts/DL1, 3 pts/DL2, 6 pts/DL3, 6 pts/DL4), 17 pts are currently evaluable: median age 66 years, median PSA 250 μg/L, metastatic sites to bone and/or lymph nodes (17), visceral (2), prior chemotherapy 5 pts. The median number of treatment cycles was 6 (range 2–10). 2 pts experienced DLT (1 febrile neutropenia/DL 3 and 1 diarrhea/grade 4 neutropenia at DL4); these dose levels were expanded to 6 pts with no further DLT. Hematologic toxicities include febrile neutropenia (2 pts), grade 3/4 neutropenia (7 pts). Additional non-hematologic toxicities were grade 1/2 beside 1 episode of grade 3 diarrhea and lethargy each. AUC and Cmax for A were similar to single-agent data. AUC and Cmax for D appeared independent of ABT-751 dosing. PSA decline of ≥50% occurred in 10/16 evaluable pts (63%), ≥30% in 14/16 pts (89%) and <30% in 2/16 pts as best response thus far. Best response per RECIST in 12 pts with measurable disease was partial response in 4 pts (33%) and stable disease in 8 pts (67%). Conclusions: The combination of ABT-751 and docetaxel is well tolerated at the tested doses. PK results suggest no significant PK interaction. Early findings indicate encouraging clinical activity of the combination treatment. Extended accrual to the recommended phase II dose is ongoing to further define activity and toxicity. No significant financial relationships to disclose.

A multicenter phase IIb trial to evaluate the efficacy and tolerability of ModraDoc006/r in subjects with metastatic castration-resistant prostate cancer (mCRPC), suitable for treatment with a taxane (NCT04028388).

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. TPS268-TPS268
Author(s):  
Ulka N. Vaishampayan ◽  
Edwin J. De Wit ◽  
Neal D. Shore ◽  
Robert Dreicer ◽  
Daniel J. George ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Oral Prednisone ◽  
Objective Response ◽  
Cancer Therapeutics ◽  
Standard Of Care ◽  
Primary Objective ◽  
Castration Resistant Prostate Cancer ◽  
Open Label ◽  
Oral Tablet ◽  
Patient Reported

TPS268 Background: Docetaxel IV and prednisone is a standard of care in mCRPC with demonstrated overall survival benefit. ModraDoc006 is a novel oral tablet formulation of docetaxel and to enhance bioavailability, it is co-administered with ritonavir (/r), an inhibitor of cytochrome p450 3A4 and P-glycoprotein. The oral combination, denoted as ModraDoc006/r, could be preferable due to patient convenience and elimination of infusion reactions and prophylactic steroids administration. Due to its weekly administration and exposure levels, increased efficacy may be demonstrated. Methods: The study is an open label 1:1 randomized phase 2b trial of ModraDoc006/r bi-daily QW versus docetaxel IV 75 mg/m2 Q3W. Thirty (30) mg ModraDoc006 combined with 200 mg /r in morning and 20 mg ModraDoc006 with 100 mg /r in evening is administered on days 1, 8 and 15 of a 21 day cycle. Safety and preliminary efficacy of ModraDoc006/r have been established in a phase Ib trial in mCRPC pts. All patients will receive 5 mg oral prednisone twice daily. Treatment is continued until progression, unacceptable toxicity or patient wish. mCRPC pts with measurable disease per RECIST 1.1, suitable for docetaxel therapy, are eligible. No prior treatment with taxanes is allowed. Primary objective is objective response rate (ORR) as assessed by investigators. Secondary objectives include PSA response, PSA-PFS, time to skeletal related events and progression, duration of response, disease control rate and safety assessments. Patient reported outcomes and health-related quality of life will be captured with treatment satisfaction and FACT-P questionnaires. It is expected that ModraDoc006/r will be at least as effective as docetaxel IV. A sample size of 50 evaluable pts per arm will evaluate an estimated ORR of 25% in each arm, with a 5% two-sided alpha and power of 83.7%. Conclusions: ModraDoc006/r represents an advance in prostate cancer therapeutics with convenience of oral administration, reduced myelosuppressive toxicity and potential improved efficacy over IV docetaxel. Clinical trial information: NCT04028388.

The combination of venetoclax, lenalidomide, and rituximab in patients with newly diagnosed mantle cell lymphoma induces high response rates and MRD undetectability.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 7505-7505
Author(s):  
Tycel Jovelle Phillips ◽  
Alexey Valeryevich Danilov ◽  
David Alan Bond ◽  
Alex Francisco Herrera ◽  
Kami J. Maddocks ◽  
...  
Keyword(s):  
Phase 1 ◽  
Safety Data ◽  
Standard Of Care ◽  
Primary Objective ◽  
Clinical Activity ◽  
Newly Diagnosed ◽  
Grade 5 ◽  
Unrelated Condition ◽  
Mantle Cell ◽  
Grade 3

7505 Background: MCL is a rare lymphoma without a standard of care but several regimens have demonstrated clinical activity, the majority based on traditional chemotherapy. We hypothesized that adding venetoclax (V) to R2 would be safe and effective in MCL pts irrespective of age, morphology or stage. Here we present safety and efficacy data from the on-going phase 1b study of R2 + V in pts with newly diagnosed MCL. Methods: This multi-center phase 1 study (NCT03523975) enrolled pts aged ≥18 yrs with untreated MCL. The primary objective was to characterize the safety and tolerability of R2 + V and determine the MTD. During induction (12 months (m)) pts received lenalidomide (L) 20 mg daily on day 1-21, Rituximab (R) was given weekly during c1 then on day 1 of every even cycle, V was escalated over 4 weeks to 400 mg beginning day 8. Each cycle is 28 days (d). The DLT period was 42 d beginning C1D8. In maintenance, R every 8 weeks for 36m, L at 10 mg or half of last dose during induction for 24 m and V for minimum 12 m. No pts have been transplanted. Pts with progression (PD) came off study. MRD was analyzed in parallel with scans during induction by clonoSEQ assay (Adaptive Biotechnologies). Results: As of Feb. 1st, 2021, we have enrolled all 28 planned pts on study. Pt characteristics/responses are summarized in Table. Among the 28 pts who have received at least one dose, the median treatment duration so far is 278d (IQR 170-560), with 24 pts still on treatment (Tx). 1 pt is off from a unrelated condition. All pts escalated to V 400 mg w/o any DLTs noted. Treatment-emergent adverse events (TEAEs) were reported in 100% of pts, and grade 3+ TEAEs were reported in 26 (93%) patients. The most common all-grade TEAEs (≥50% of pts), regardless of relationship to study Tx, were fatigue, neutropenia and diarrhea. Grade ≥3 TEAEs reported in ≥50% pts were neutropenia (68%) and thrombocytopenia (50%). No pts have withdrawn or d/c Tx due to AEs. There was one grade 5 event, in a non-evaluable pt, related to a PE that occurred prior to DLT period. In the 28 evaluable pts the ORR (CR/PR) was 96% (27/28 pts) with CR/CRu of 89%. Of the responding pts, two had PD, one w/ CR and one w/ PR. All pts with PD had baseline TP53 mutation. MRD testing was successful in all pts. At time of submission 20 of 28 (71%) were MRD - at 10-6. Conclusions: Interim results show that at the MTD the combination of V 400 mg daily, L 20 mg, with R is safe with a manageable toxicity profile and a high ORR and MRD - in pts with newly diagnosed MCL. Safety data is consistent with the AE profile noted for each drug without any unexpected or unique AEs. Updated results including BH3 profiling will be presented at the meeting. Clinical trial information: NCT03523975. [Table: see text]

Phase II study of intravenous vinorelbine plus hormone therapy in hormone-refractory prostate cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14601-14601
Author(s):  
E. Silva ◽  
F. Silva
Keyword(s):  
Prostate Cancer ◽  
Elderly Patients ◽  
Prostate Specific Antigen ◽  
Phase Ii ◽  
Performance Status ◽  
Specific Antigen ◽  
Hormone Refractory Prostate Cancer ◽  
Phase Ii Studies ◽  
Hormone Refractory ◽  
Grade 3

14601 Background: Vinorelbine (VRL) has been shown to be active in hormone-refractory prostate cancer (HRPC) in Phase II studies, alone or in combination. Its moderate toxicity profile is well tolerated in elderly patients. The purpose of this study was the investigation of the efficacy of vinorelbine and its toxicity. Methods: Patients with metastatic prostate cancer, progressive after hormonal therapy, receive intravenous VRL 30 mg/m2 on days 1 and 8 every 3 weeks, and hydrocortisone 40 mg/day. Previous chemotherapy was allowed if stopped 6 months before. 44 received VRL according to the protocol. Inclusion criteria: hormone refractory prostate cancer patients PSA >20; performance status WHO < 2. The primary endpoint was prostate specific antigen (PSA) levels, pain, and WHO performance status. Their mean (range) age was 71 (45–80) years, their median prostate specific antigen (PSA) level was 286 (38–950) ng/ml, and the median Gleason score was 8 (7 to 9). 38 patients had had previous chemotherapy. Results: Among the 44 patients, 7 with less than 3 cycles were not evaluated. Patients received a mean (range) of 9 (3–44) cycles of therapy. 6 patients (14%) had not been dispensed prior chemotherapy and 38 (86%) had; 19 (43%) had 2 lines of chemotherapy and 19 (43%) had 1 line. The median follow-up was 13 months. There were no reported drug related Grade 3 toxicities. Only 2 patients required a blood transfusion. Tumour responses: 7 (16%); 17 (39%) PSA stable; 13 (29%) PSA progression, 7 not evaluated. Time of PSA response was 7 months; time to progression: 7 months. Conclusions: Vinorelbine (VRL) is a safe regimen in previous poly-chemotherapy treated hormone-refractory prostate cancer elderly patients and even with response and efficacy. No significant financial relationships to disclose.

A phase II study of a weekly schedule of BMS-247550 for patients with hormone-refractory prostate cancer: A trial of the Eastern Cooperative Oncology Group (E3803)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4618-4618 ◽  
Author(s):  
G. Liu ◽  
W. Wang ◽  
R. Dipaola ◽  
M. Carducci ◽  
G. Wilding
Keyword(s):  
Prostate Cancer ◽  
Eastern Cooperative Oncology Group ◽  
Safety Data ◽  
Response Assessment ◽  
Entire Group ◽  
Hematologic Toxicity ◽  
Weekly Schedule ◽  
Hormone Refractory Prostate Cancer ◽  
Hormone Refractory ◽  
Grade 3

4618 Background: BMS-247550 (ixabepilone) is an epothilone B analogue with activity in taxane-resistent cancer cell lines. Ixabepilone has been administered using a q3wks schedule with significant neutropenia observed. Here we assess the activity and toxicity of ixabepilone, administered using a weekly schedule, in men with metastatic hormone-refractory prostate cancer. Methods: Patients with metastatic hormone-refractory prostate cancer (chemonaive and prior taxane) were treated with ixabepilone at 20 mg/m2 IV weekly × 3, in 4 wk cycles. This non-comparative study had a planned accrual of 29 chemonaive and 27 prior-taxane treated patients in order to detect a 50% PSA reduction using Consensus Criteria in at least 50% (91% power, α = 0.10) chemonaive and 30% (power 90%, α = 0.10) prior-taxane treated patients. Results: 32 pts with chemonaive and 37 pts with prior-taxane have been enrolled on this study. Median follow-up is 1.8 and 4.1 months respectively. Safety data is reported for the first 56 subjects (24 chemonaive and 32 prior taxane). Hematologic toxicity: Grade 3/4 neutropenia was seen in 10 pts (5 chemonaive, 5 prior-taxane). No significant thrombocytopenia was observed. Grade 3/4 neuropathy was seen in 7 pts (2 chemonaive, 5 prior-taxane). Grade 3 fatigue noted in 8 (3 chemonaive, 5 prior-taxane), grade 3 diarrhea in 5 (4 chemonaive, 1 prior-taxane), and grade 3 nausea in 3 subjects. Lastly, 2 subjects were reported to have developed a grade 3 ileus during therapy. Conclusions: In 56 subjects, BMS-247550 was found to have an acceptable toxicity profile when administered using a weekly schedule. Myelosuppression appeared to be improved, as compared to historical data with the q3wk schedule, using this dose and schedule. PSA/objective responses have been seen but at this time, no conclusion regarding its activity in the first or second-line setting can be made, as the response assessment is ongoing. Complete toxicity and response data will be presented for the entire group. No significant financial relationships to disclose.

A phase II trial of 17-allylamino-17-demethoxygeldanamycin (17-AAG) in patients with hormone-refractory metastatic prostate cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15553-15553 ◽  
Author(s):  
E. I. Heath ◽  
D. Hillman ◽  
U. Vaishampayan ◽  
S. Sheng ◽  
F. H. Sarkar ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Biology ◽  
Progression Free Survival ◽  
Fold Increase ◽  
Median Number ◽  
Serum Markers ◽  
Primary Objective ◽  
Psa Response ◽  
Hormone Refractory ◽  
Prior Systemic Therapy

15553 Background: 17-Allylamino-17-Demethoxygeldanamycin (17-AAG) is a benzoquinone ansamycin antibiotic with anti- proliferative activity in several mouse xenograft models including prostate cancer models. Serum IL-6, IL-8, and maspin are potentially important markers of prostate cancer biology. Methods: Patients (pts) with metastatic, hormone-refractory prostate cancer progressing on at least one prior systemic therapy with rising PSA were eligible. All pts received 17-AAG at a dose of 300 mg/m2 IV weekly for three out of four weeks. Primary objective was to assess the PSA response (50% decrease in PSA). Secondary objectives included Adverse Events (AEs) and correlative serum markers including IL-6, IL-8 and maspin levels. A Simon two-stage design required a total of 25 pts with early termination if < 2 responses occurred among the 1st 16 eligible patients. Results: Seventeen pts were enrolled of which 15 were deemed eligible. Median age was 68 and median PSA was 252 ng/mL. Pts received 17-AAG for a median number of 2 cycles. No pt had a PSA response. No grade 4/5 AEs occurred. Grade 3 AEs included fatigue (4 pts), lymphopenia (2 pts) and back pain (2 pts). The median PSA progression free survival was 1.8 months (95% CI: 1.3–3.4 months). The six-month overall survival was 61% (95% CI: 37%-100%). Due to the lack of PSA response, accrual was stopped per study design. At day 15, the median IL-6 and IL-8 increase from baseline was 0.4 pg/ml (p=0.57) and 3 pg/ml (p=0.73), respectively. Maspin levels had day 15 increase of 6-fold (p=0.44). At treatment failure (TF), the median IL-6 increase from baseline was 4.47 pg/ml (p=0.03) and IL-8 decrease was 1.8 pg/ml (p=0.31). Maspin levels had a 29-fold increase at TF (p=0.09). Conclusions: 17-AAG did not show any activity with regards to PSA response. Serum IL-6 was significantly increased at the time of TF. Further evaluation of 17-AAG at a dose of 300 mg/m2 IV weekly in this patient population is not warranted. No significant financial relationships to disclose.

Dose finding and safety analysis of inecalcitol in combination with a docetaxel-prednisone regimen in hormone-refractory prostate cancer (HRPC) patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5151-5151
Author(s):  
J. Medioni ◽  
G. Deplanque ◽  
T. Maurina ◽  
J. M. Ferrero ◽  
J. M. Rodier ◽  
...  
Keyword(s):  
Human Cancer ◽  
Oral Prednisone ◽  
Dose Finding ◽  
Antiproliferative Effects ◽  
Human Cancer Cell Lines ◽  
Psa Response ◽  
Hormone Refractory ◽  
Grade 3 ◽  
Dose Levels ◽  
Health Deterioration

5151 Background: Inecalcitol is a novel synthetic vitamin D3 analogue with potent antiproliferative effects in human cancer cell lines and a 100-fold lower hypercalcemic activity than calcitriol in animal models. Methods: Escalating dosages of inecalcitol were combined to chemotherapy in naive HRPC patients (pts). Safety and efficacy were evaluated in groups of 3–6 patients receiving oral inecalcitol daily or every other day on a 21-day cycle in combination with docetaxel (75mg/m2 q3w) and oral prednisone (5mg bid). Biphosphonates were prohibited during the first cycle. Patients received up to six cycles unless unacceptable toxicity or disease progression. Primary endpoint was dose limiting toxicity (DLT) defined as grade 3 hypercalcemia within the first cycle. Calcemia, creatininemia and CBC were assessed weekly; biochemistry, ECG and PSA every 3 weeks. Efficacy endpoint was PSA response defined as ≥30% decline within 3 months. Results: Five dose levels: 40, 80, 160, 300, 600 μg have been evaluated in 34 pts; 9 pts are still being treated at 600 μg; 25 pts have completed 6 cycles (13 bone metastases; 3 extrasqueletic metastasis, 8 bone and extrasqueletic metastases; 1 PSA-only disease). Median age was 72 years (range, 53–87), median Gleason score (Gs) 7 (36% Gs 10–8, 64% Gs 7–6) and median PSA 41.5 ng/mL (range, 0.9–962.4). No increased calcemia was reported. Most adverse events (AE) were G1–2, asthenia (19pts), constipation (14pts), diarrhea (13pts). G3–4 AEs were neutropenia (11pts) lymphopenia (9pts), asthenia (3pts), arrhythmia (2 pts), general health deterioration (2pts) and diarrhea (1pt). None of these AEs was considered related to inecalcitol. Of the 23 evaluable pts for PSA response, 20 (87%) had ≥30% PSA decline. Conclusions: Results from this ongoing study show the safe profile of inecalcitol when given daily in in HRPC pts. PSA responses with this combination are encouraging. As DLT was not reached, a higher dose of inecalcitol (1000 μg/day) will be further tested. [Table: see text]

Safety and efficacy of AMG 655 plus modified FOLFOX6 (mFOLFOX6) and bevacizumab (B) for the first-line treatment of patients (pts) with metastatic colorectal cancer (mCRC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4079-4079 ◽  
Author(s):  
L. Saltz ◽  
J. Infante ◽  
L. Schwartzberg ◽  
J. Stephenson ◽  
C. Rocha-Lima ◽  
...  
Keyword(s):  
Disease Progression ◽  
Human Monoclonal Antibody ◽  
Single Agent ◽  
Objective Response ◽  
Death Receptor ◽  
Maximum Tolerated Dose ◽  
Primary Objective ◽  
Death Receptor 5 ◽  
Grade 3 ◽  
Ecog Ps

4079 Background: AMG 655 is an investigational fully human monoclonal antibody (IgG1) agonist of human death receptor 5 (DR5). AMG 655 activates caspases and induces apoptosis in sensitive tumor cells. The primary objective of this phase 1b study was to determine the maximum tolerated dose (up to a target dose of 10 mg/kg IV every 2 weeks) of AMG 655 that can be safely administered in combination with mFOLFOX6-B to mCRC pts. Methods: Eligible pts were ≥ 18 years old with previously untreated mCRC, ECOG PS of 0 or 1, and adequate hematologic, hepatic, and renal function. Pts were enrolled into sequential cohorts of 3- or 10-mg/kg AMG 655 + mFOLFOX6-B administered on day 1 of each 14-day cycle. Study endpoints included incidence of dose-limiting toxicities (DLT), adverse events (AE), pharmacokinetic (PK) parameters of AMG 655, and objective response rate (by modified RECIST). Results: As of 09/08, 12 pts (6 per cohort) were enrolled and received ≥ 1 cycle of treatment; 8 were female. Median (range) age was 54 (37–75), median (range) time on AMG 655 treatment was 6.9 (1.6 to 11.4+) months; 8 pts continue on study treatment. There were no DLTs in the first 28 days of treatment. Eight pts had grade 3–4 AE; the most common were diarrhea, febrile neutropenia, peripheral neuropathy, neutropenia, DVT, and pulmonary embolism (2 pts each). Post baseline laboratory parameters grade ≥ 3: no ALT and AST; 1 grade 3 bilirubin (due to disease progression), and 3 grade 3 lipase (asymptomatic). No anti-AMG 655 antibodies were detected. AMG 655 PK values (Cmax, Cmin) were similar to those observed with single-agent AMG 655 (LoRusso JCO 2007; 25: abstract 3534). AMG 655 did not appear to affect PK of oxaliplatin or bevacizumab. Best overall tumor response: 5 partial responses (2 unconfirmed, both underwent resection); 6 stable disease; 1 pt had non-measurable disease at baseline. Time to disease progression (3 patients): 8, 42, and 44 weeks. Conclusions: The addition of AMG 655 does not appear to substantially alter the safety profile of mFOLFOX6-B. The randomized phase 2 part of the trial (mFOLFOX6-B ± AMG 655) is in progress. [Table: see text]

CA184-156: A randomized, multicenter, double-blind, phase III trial comparing the efficacy of ipilimumab (Ipi) plus etoposide/platinum (EP) versus EP in subjects with newly diagnosed extensive-stage disease small cell lung cancer (ED-SCLC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS7113-TPS7113 ◽  
Author(s):  
David R. Spigel ◽  
Christoph Zielinski ◽  
Sabine Maier ◽  
Veerle de Pril ◽  
Justin P. Fairchild ◽  
...  
Keyword(s):  
Immune Response ◽  
Human Monoclonal Antibody ◽  
Study Drug ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Primary Objective ◽  
Phase Iii ◽  
Response Patterns ◽  
Double Blind ◽  
Blinded Study

TPS7113 Background: EP (4-6 cycles) is standard of care 1st-line therapy for metastatic SCLC, and no multinational studies have reported any improvement beyond that reported for EP. Evidence of an ongoing immune response to SCLC tumors suggests that immunotherapy that enhances this immune response to SCLC may enhance the clinical benefit of EP. Ipi, a fully human monoclonal antibody which blocks CTLA-4, augments antitumor immune responses. Because some responses to Ipi may differ from those observed with cytotoxic therapies, immune-related response criteria (irRC) were derived from WHO criteria to better capture response patterns observed with Ipi. A randomized Phase 2 study of Ipi with paclitaxel/carboplatin (PC) in pts with ED-SCLC showed significant improvement in progression-free survival (PFS), as measured by irRC, over PC alone in pts receiving Ipi and PC in a phased regimen (Ipi started after 2 cycles of PC). Furthermore, addition of Ipi did not exacerbate PC toxicity, and immune-related adverse events were managed using protocol-specific guidelines. This multicenter phase III study in pts with ED-SCLC (ClinicalTrials.gov identifier NCT01450761) will determine whether adding Ipi to EP increases OS vs EP alone. Methods: EP consists of 4 cycles of etoposide (100 mg/m2, IV on Days 1-3 every 3 weeks [Q3W]) and cisplatin (75 mg/m2, IV) or carboplatin (AUC=5, IV) once Q3W. Pts will be randomized to receive 4 doses of Ipi (10 mg/kg, IV) in Arm A or placebo in Arm B, Q3W during induction, starting after 2 cycles of EP (phased schedule). Eligible pts will then receive blinded study drug (Ipi in Arm A; placebo in Arm B) Q12W until disease progression or unacceptable toxicity. The primary objective is to compare OS. Secondary objectives are to compare OS in those who receive blinded study drug, compare PFS between study arms, and to estimate best overall response rate and duration of response. First-line ED-SCLC pts with ECOG performance ≤1 will be included. Pts with symptomatic CNS metastases or a history of autoimmune disease will be excluded. The study will randomize 1100 pts at a 1:1 ratio.

Vinorelbine and Prednisone in older Cancer Patients with Hormone-Refractory Metastatic Prostate Cancer a Phase II Study

2003 ◽  
Vol 89 (1) ◽  
pp. 26-30 ◽  
Author(s):  
Paolo Tralongo ◽  
Roberto Bollina ◽  
Rosanna Aiello ◽  
Anna Di Mari ◽  
Giovanni Moruzzi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Patients ◽  
Clinical Benefit ◽  
Entire Group ◽  
Common Disease ◽  
Hormone Refractory Prostate Cancer ◽  
Elderly Cancer Patients ◽  
Older Cancer Patients ◽  
Hormone Refractory ◽  
Grade 3

Aims and Background Prostate cancer is a common disease in older men. Since it is hormone resistant, no treatment may improve survival. In patients with hormone-refractory prostate cancer, clinical benefit is an important treatment end point. Study Design This study evaluated the efficacy and toxicity of a vinorelbine and prednisone combination in hormone-refractory prostate cancer patients. Vinorelbine was administered at the dose of 25 mg/m2 on days 1 and 8, every three weeks; prednisone was administered orally at the dose of 12 mg/day. Thirty consecutive patients, 65 years or older, with progressive (PSA increase or increase in bidimensionally measurable lesion) metastatic prostate adenocarcinoma were enrolled. Four patients (13%) had a partial response and 14 (46%) stable disease. Time to progression for the entire group was 4.5 months (range, 2–13) and 7.5 months for the group of responders (range, 3–13). A PSA decrease >50% was registered in 36% of the patients. Pain reduction was recorded in 44.4% of the patients and stability in 14.8%. Results The treatment was well tolerated and grade 3 toxicity was found in 2 cases of anemia and 2 cases of leukopenia without fever. Conclusions The schedule is able to control the evolution of hormone-refractory prostate cancer and to give a clinical benefit. These results provide information for further clinical trials in a large series of elderly cancer patients.

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