Phase I/II studies

Balan V Nelson DR, Sulkowski MS, Everson GT, Lambiase LR, Wiesner RH, Dickson RC, Post AB, Redfleld RR, Davis GL, Neumann AU, Osborn BE, Ereimuth WW, Subramanian GM (2006) A Phase I/II study evaluating escalating doses of recombinant human albumin-interferon-alpha fusion protein in chronic hepatitis C patients who have failed previous interferon-alpha-based therapy, Antivir Ther 11 35 5... 

Sugiura T, Ariyoshi Y, Negoro S, Nakamura S, Ikegami H, Takada M, Yana T, Fukuoka M. (2005) Phase I/II study of amrubicin, a novel 9-aminoan-thracycline, in patients with advanced non-small-cell lung cancer. Invest New Drugs 23 331-337. 

Quintas-Cardama A, Kantaijian H, Garcia-Manero G O Brien S, Faderl S, Estrov Z, Giles F, Murgo A, Ladie N, Verstovsek S, Cortes J. (2007) Phase I/II study of subcutaneous homoharringtonine in patients with chronic myeloid leukemia who have failed prior therapy. Cancer 109 248-255. 

AstraZeneca also entered a molecule (AZD-3409) (Fig. 4) into phase I/II studies [180]. AZD-3409 is a double prodrug inhibiting both FTase and GGTase I. AZD-3409 is converted in vivo into a prodrug, the main component in plasma of dosed animals, which is further metabolized in cells to the active drug. Recently published phase I data indicate that AZD-3409 was well... 

Takeda et al. (64) performed a phase I/II study consisting of low-dose CDDP (6-10 mg/m2/d) and UFT (600 mg/d) combined with radiotherapy (50 Gy/25 fractions) as postoperative adjuvant therapy following curative resection for patients with nonsmallcell lung cancer (NSCLC). The combined therapy was well tolerated and resulted in a disease-free survival rate of 78% at 2 yr. Another study in a small number of patients with unresectable stage III nonsmall-cell lung cancer, UFT (400 mg/m2 on d 1-52) and CDDP (80 mg/m2 on d 8,29, and 50) were administered with radiation therapy (total dose of 60.8 Gy in 38 fractions on d 1-52). Among 17 evaluable patients, 94% (16 patients) achieved partial responses with median time to tumor progression of 30 wk, and the... 

Segawa Y, Ueoka H, Kiura K, et al. A phase I/II study of docetaxel (TXT) and cisplatin (CDDP) with concurrent thoracic radiotherapy (TRT) for locally advanced non-small-cell lung cancer (LA-NSCLC). ProcAm Soc Clin Oncol 2000 19 508a. 

GOG-9803 Phase I/II Study of Radiotherapy Combined With Paclitaxel and Cisplatin in Patients With Stage IB2, IIA, IIB, IIIB, or IVA Invasive Carcinoma of the Cervix. 

GOG-9804 Phase I/II Study of Extended Field Radiation Therapy With Concurrent Paclitaxel and Cisplatin Chemotherapy in Patients With Previously Untreated Carcinoma of the Cervix Metastatic to the Para-aortic Lymph Nodes. Study Protocol, http //www.cancer.gov/search/clinical trials... 

Several other small phase I or phase I/II studies looking at the concurrent administration of gemcitabine and radiation with or without other agents have been reported in abstract form (Table 3). In general these trials illustrate that gemcitabine can be safely administered with radiation in NSCLC patients. However, their small numbers and the fact that they are reported from only a few select institutions have not fully conquered the fears that many have about concurrent administration of this agent with radiation. 

Blackstock AW, Lesser G, Tucker G, et al. Twice-weekly gemcitabine and concurrent thoracic radio-therapy-a phase I/II study in patients with advanced nonsmall-cell lung cancer. Pro Am Soc Clin Oncol 2000 19 47a (abstract 1846). 

Kudromoti M, Regine W, John W, et al. Concurrent infusional gemcitabine and radiation in the treatment of advanced unresectable GI malignancy A phase I/II study. Proc Am Soc Clin Oncol 1999 18 242a. 

The RTOG has recently reported on RTOG 96-10, a phase I/II study of a split-course chemoradiation schedule of concomitant hydroxyurea (2000 mg prior to second daily radiation dose, d 1-5), 5-FU (300 mg/m2 iv bolus prior to second daily radiation dose, d 1-5), and twice-daily hyperfractionated radiation therapy (1.5 Gy/fraction, d 1-5) to be administered wk 1, 3, 5, 7 (83). Seventy-nine percent of the patients received all four cycles. Treatment delays of at least one week were required in 32% of patients. Six patients died from treatment-related toxicity. Of 81 evaluable patients, common grade 3/... 

Jacobs MC, Eisenberger M, Oh MC, et al. Carboplatin (CBDCA) and radiotherapy for stage IV carcinoma of the head and neck a phase I-II study. Int J Radiat Oncol Biol Phys 1989 17 361-363. 

Irinotecan is an active chemotherapeutic agent that has been used in esophageal cancer and is also a potent radiosensitizer. In vitro studies have shown activity in esophageal cancer cell lines. A Phase I study has demonstrated its safety and tolerability with cisplatin. Phase I/II studies are currently underway determining the maximum tolerated weekly dose of irinotecan combined with concurrent radiation for locally advanced esophageal cancer (MSKCC 99081). 

Gaspar LE, Winter K, Kocha WI, Coia LR, Herskovic A, Graham M. A phase I/II study of external beam radiation, brachytherapy, and concurrent chemotherapy for patients with localized carcinoma of the esophagus (Radiation Therapy Oncology Group Study 9207) final report. Cancer 2000 88(5) 988-995. 

The two consecutive chemo-RT Phase I-II studies conducted showed that different molecular markers were associated with pathological response The finding supports the hypothesis that different drugs combined with concurrent radiation are effective on different tumor types. If this hypothesis is correct, selecting up-front which patient should be treated with one type of chemo-RT vs the other, based on the molecular characteristics of the tumor, may optimize pathological response rates, thus potentially reflecting on... 

Pathological Response and Outcome in Phase I-II Studies of LABC... 

Hidalgo M, et al. Phase I-II study of gemcitabine and fluorouracil as a continuous infusion in patients with pancreatic cancer. J Clin Oncol 1999 17(2) 585—592. 

Koizumi W, Tanabe S, Saigenji K et al. Phase I/II study of S-1 combined with cisplatin in patients with advanced gastric cancer. Br J Cancer 2003 89 2207-2212. 

Maker AZ et al Tumor regression and autoimmunity in patients treated with cytotoxic T lymphocyte-associated antigen 4 blockade and interleukin 2 A phase I/II study. Ann Surg Oncol 2005 12 1004. 

Bukowski, R., Ernstoff, M. S., Gore, M.E., et al. PEGylated interferon alfa-2b treatment for patients with solid tumors A phase I/II study. J. Clin. Oncol. 20(18) 3841-3849. 2002. 

Wagner, J. A. et al. (1998). A phase I/II study of tgAAV-CF for the treatment of chronic sinusitis in patients with cystic fibrosis. Hum. Gene Ther. 9, 889-909. 

Another anti-CD20 radioimmunoconjugate, IDEC-Y2B8, is a 90Yt-labeled version of the murine mAh parent of rituximab. In a phase I—II study, B-cell NHL patients received an initial dose of unlabeled rituximab to clear peripheral B cells and improve biodistribution of the RIT mAh, followed by escalating doses of IDEC-Y2B8, (179). 

A phase I/II study to evaluate the safety, immunogenicity, pharmacokinetics and potential efficacy of iv rhuTNF binding protein pegylated dimer in patients with active RA. Arthritis Rheum. 41, S58 (abstract). 

Cooper, C.L., Davis, H.L., Morris, M.L., Eller, S.M., Adhami, M.A., Krieg, A.M., Cameron, D.W., Heathcote, J. CPG 7909, an immunostimulatory TLR9 agonist oligodeoxynucleotide, as adjuvant to Engerix-B HBV vaccine in healthy adults A double blind phase I/II study. J Clin Immunol 24 (2004) 693-701. 

A phase I/II randomized clinical trial compared ranibizumab injections, given at 4-week intervals, with usual care (control arm) in 64 subjects with predominantly classic or minimally classic AMD. The drug appeared to be effective for both types of AMD as evidenced by improvements in visual acuity at 3 and 6 months and was found to have an acceptable tolerability profile. Subjects with less than 15 letters of acuity at the end of the phase I/II study were followed for over 1 year, but the fixed dosing interval of every 4 weeks was relaxed to a more flexible strategy of holding a dose if acuity was stable (with a change of less than 5 letters) and lesion characteristics were stable on two consecutive visits. Acuity and lesion characteristics continued to be stable in subjects, and the median dosing rate of 1.0 injection every 4 weeks decreased to 0.22 injections every 4 weeks. 

Gordon PH, Moore DH, Gelinas DF, Qualls C, Meister ME, Werner J, Mendoza M, Mass J, Kushner G, Miller RG (2004) Placebo controlled phase I/II studies of minocycline in amyotrophic lateral sclerosis. Neurology 62 1845—1847. 

To date, one clinical dial has evaluated the role of nimocUpine in the heatment of HAD. A multicenter phase I/II study by the AIDS CUnical Trial Group enrolled 4l patients with cUfferent degrees of HAD (Navia et al., 1998). Patients were assigned to one of three arms placebo, nimocUpine 30mg orally del or nimocUpine 50 mg five times a clay for 16 weeks. Patients in all arms received an NRTI (ziclovucUne, cUclanosine... 

Tyndall A, Saccradi R (2005) Haematopoietic stem cell transplantation in the treatment of severe autoimmune disease Results from phase I/II studies, prospective randomized trials and future directions. Chn Exp Immunol l(l) l-9. 

In a subsequent Phase I/II study that allowed for dose escalation and extended duration of dosing, patients with shock secondary to sepsis or presumed sepsis received a dose of Hb-PHP of 160, 320, 640, or 2560mgHb/kg body weight.Dosing was initiated at a rate of lOmgHb/kg/h and increased in increments of lOmg/kg/h at 15 min intervals to a maximum rate of 20, 40, or 80mgHb/kg/h for the lowest, middle, or two... 

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