Clinical trial NCT04931823: Dose Escalation and Dose Expansion Study of CPO-100 in Patients With Advanced Solid Tumors
Official title: A Phase 1, Multicenter, Single Agent Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Evidence of Antitumor Activity of CPO-100 in Adult Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Solid Tumor
Keywords: Breast Cancer
Prostate Cancer
Gastric Cancer
Lung Cancer
Head and Neck Cancer
Ovarian Cancer
Docetaxel
Docetaxel albumin-bound
DTX-HSA
CPO-100
Phase 1
Taxane Naïve
Solid Tumor
Stage 4
Metastatic Cancer
Cancer
Advanced Cancer
Taxane
Non-resectable tumor
Lead sponsor: Conjupro Biotherapeutics, Inc.
Sponsor class: INDUSTRY
Collaborators: name: CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
First posted: 2021-06-18
Enrollment: 126
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Modified "3+3" dose escalation design followed by dose expansion at the MTD (maximum tolerated dose).
Primary purpose: TREATMENT

Brief summary: This is a Phase 1, multicenter, open-label, dose escalation and dose expansion study to evaluate the safety, tolerability, pharmacokinetics, and preliminary evidence of antitumor activity of CPO-100 administered intravenously in cycles of 3 weekly doses with 1 week rest (1 cycle = 4 weeks) in adult patients with advanced solid tumors.

Detailed description: The study has three parts. Part A-1 is a dose-escalation phase with a modified "3+3" design in patients with metastatic or unresectable advanced solid tumors to evaluate the safety, tolerability and pharmacokinetics (PK) as a single agent. Two patients will be enrolled at each of the first 2 dose levels and observed for safety during the first cycle. If there are no ≥Grade 2 treatment emergent adverse events (TEAE) that are clinically significant and attributed to the study drug as assessed by the investigator during Cycle 1 for any of the patients in the first two dose levels, the 3rd dose level and beyond will follow the traditional 3+3 design. Dose escalation during the "3+3" period for each subsequent cohort of patients will be guided by the incidence of CPO-100-related adverse events (AE) as graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) CTCAE v5.0 in the first 4 weeks of dosing \[the Dose Limiting Toxicity (DLT) evaluation period\].

In Part A-2, the starting dose for this part will be 45 mg/m2. This dose was established in Part A-1 as being that dose at which the use of Granulocyte-colony stimulating factor ()G-CSF is indicated given that the only Grade 3 treatment-related adverse events noted were related to neutropenia and was well managed with G-CSF support. Prophylactic use of G-CSF will be permitted in Cycle 1 based on the investigator judgement.

This additional intervention of primary prophylaxis will be explored in order to determine if the risk of febrile neutropenia (FN) under these circumstances is reduced. Dose escalation during the 3+3 period for each subsequent cohort of patients will be guided by the incidence of CPO-100-related adverse events (AE) as graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0 in the first 4 weeks of dosing (the DLT evaluation period).

After the Maximum Tolerated Dose (MTD) of weekly dosing schedule has been established, a recommended Phase 2 dose will be selected based on evaluation of the PK, and safety and tolerability profile on all available Part A study data by the Safety Review Committee (SRC). The selection of the Recommended Phase 2 Dose (RP2D) will consider all available clinical and non-clinical CPO-100 data as well as relevant docetaxel published data.

Part B expansion phase will further evaluate the safety and tolerability as well as the preliminary antitumor activity at the selected RP2D. Four cohorts of patients are included in Part B:

* Cohort 1: taxane naïve advanced/metastatic gastric, head and neck, lung, and ovarian cancers
* Cohort 2: taxane naïve advanced/metastatic breast cancer
* Cohort 3: taxane naïve advanced /metastatic prostate cancer
* Cohort 4: advanced/metastatic breast or ovarian cancer who have either progressed on a taxane or have developed progressive disease within 6 months of receiving a taxane.

The taxane naïve patient population is defined as patients who have not received taxane or taxane-based therapies for their metastatic diseases or patients who had suboptimal taxane exposure defined as having received less than 2 cycles of taxane or taxane-based therapies due to intolerability for their metastatic diseases. Patients who have received taxane or taxane-based therapies for their neoadjuvant treatment or patients who have received taxane or taxane-based therapies for their adjuvant treatment without disease progression during treatment are also considered taxane naïve, as long as they have not received taxane or taxane-based therapies to treat the metastatic diseases.

It is estimated that approximately 60 patients can be enrolled in Parts A-1 and A-2. The exact number of patients will depend on the number of dose levels tested. A total of 60 patients, 15 patients in each cohort will be enrolled in Part B.

The total duration of the study is estimated to be approximately 5 years. Patients may continue receiving CPO-100 until criteria for withdrawal are met. Patients deriving clinical benefit may continue to receive study medication for as long as they are benefiting from treatment. In the event the study closes or terminates while patients are still benefiting from and receiving CPO-100, every effort will be made to continue drug supply.

Eligibility criteria: Inclusion Criteria - Parts A-1, A-2, and B:

1. Presence of a pathologically documented (histology or cytology) locally advanced or metastatic solid tumor cancer.
2. Patients has failed at least 2 lines of conventional systemic therapy or have no other standard of care therapies available for their cancer. Prostate cancer patients should have received adenosine triphosphate (ADT) alone,(GnRH agonist, GnRH antagonist, or surgical orchiectomy and a pathway targeted agent such as abiraterone, enzalutamide, etc (castration-resistant prostate cancer). M1 disease must be present (not just biochemical recurrence).
3. Male or female patients18 years of age or older.
4. ECOG (Eastern Cooperative Oncology Group) performance status (PS) of 0, 1 or 2
5. Having at least one measurable target lesion present and documented by RECIST 1.1 for each cancer other than prostate cancer. Patients with prostate cancer may be enrolled with non-measurable disease providing the patient with a prostate-specific antigen (PSA) increase that is ≥25% and ≥2 ng/mL above the nadir, which is confirmed by a second value ≥3 weeks later, or 2 or more new bone lesions on imaging.
6. Adequate major system function defined as:

   1. Bone marrow reserve:

      Absolute neutrophil count (ANC) ≥1.5 x109/L Platelet count ≥ 100 x109/L Hemoglobin ≥9 g/dL without transfusion (the patient needs to be transfusion independent)
   2. Hepatic function:

      Total bilirubin ≤ upper limit of normal (ULN) (unless the subject has Grade 1 bilirubin elevation due to Gilbert's disease or a similar syndrome involving slow conjugation of total bilirubin); And aspartate aminotransferase (AST) / serum glutamic oxaloacetic transaminase (SGOT) and/or alanine aminotransferase (ALT) / serum glutamic pyruvic transaminase (SGPT) ≤ 1.5 x ULN with alkaline phosphatase ≤2.5 x ULN.
   3. Renal function:

      Normal serum creatinine ≤1.5 mg/dL (133 μmol/L) OR calculated creatinine clearance ≥50 mL/min. (Cockcroft - Gault formula)
   4. Coagulation:

   Adequate coagulation parameters defined as International Normalization Ratio (INR) ≤2.
7. Adequate methods of contraception for female patients of reproductive potential during the study and for at least 6 months following last dose. Male patients with female partners of childbearing potential and women patients of childbearing potential are required to use two forms of acceptable contraception, including 1 barrier method, during their participation in the study and for at least 3 months following last dose. Male patients must also refrain from donating sperm during their participation in the study.
8. Life expectancy ≥3 months.
9. Willingness and ability to comply with study and follow-up procedures.
10. Ability to understand the nature of this study and give written informed consent.

Additional Inclusion Criteria for the dose expansion cohort - Part B

1. Pathologically confirmed (histology or cytology) of the following cancer types:

   1. Cohort 1: taxane naïve advanced/metastatic gastric cancer, lung cancer, head and neck cancer, or ovarian cancer;
   2. Cohort 2: taxane naïve advanced/metastatic breast cancer;
   3. Cohort 3: taxane naïve advanced/metastatic prostate cancer.
   4. Cohort 4: advanced/metastatic breast or ovarian cancer patients who have either progressed on a taxane or have developed progressive disease within 6 months of receiving a taxane;
2. With the exception of Cohort 4 above, taxane naïve patients must not have received taxane or taxane based therapies for their metastatic diseases. Patients who had suboptimal taxane exposure defined as having received less than 2 cycles of taxane or taxane based therapies due to intolerability for their metastatic diseases, patients who have received taxane or taxane based therapies for their neoadjuvant treatment or patients who have received taxane or taxane based therapies for their adjuvant treatment without disease progression during treatment are also considered taxane naïve, as long as they have not received taxane or taxane based therapies to treat the metastatic diseases.

Exclusion Criteria - Part A and B

1. Most recent chemotherapy ≤14 days or have residual NCI CTCAE greater than Grade 1 chemotherapy-related side effects, with the exception of alopecia.
2. Use of any experimental drug ≤28 days or 5 half-lives (whichever is shorter) prior to the first dose of CPO-100. For study drugs for which 5 half-lives is ≤28 days, a minimum of 14 days between termination of the study drug and administration of CPO-100 is required.
3. Wide field radiotherapy (including therapeutic radioisotopes such as strontium 89 and lutetium 177) administered ≤28 days or limited field radiation for palliation ≤7 days prior to starting study drug or has not recovered from side effects of such therapy.
4. Major surgical procedures ≤28 days of beginning study drug, or minor surgical procedures ≤7 days. No waiting required following port-a-cath placement.
5. Previously untreated brain metastases. Patients who have received radiation or surgery for brain metastases are eligible if therapy was completed at least 2 weeks previously and there is no evidence of central nervous system disease progression, and no requirement for chronic corticosteroid therapy.
6. Leptomeningeal metastases or spinal cord compression due to disease.
7. Known serious hypersensitivity reactions to docetaxel or life-threatening toxicity due to prior exposure to docetaxel
8. Pregnant or lactating.
9. Acute or chronic liver, renal, or pancreatic disease that in the opinion of the investigator would put the patient at unjustified increased risk by participating in this study or could interfere with the interpretation of the study results.
10. Other systemic disease that in the opinion of the investigator would put the patient at unjustified increased risk by participating in this study or could interfere with the interpretation of the study results.
11. Any of the following cardiac diseases currently or within the last 6 months:

    * Left ventricular ejection fraction (LVEF) \<50% as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO)
    * Corrected QT (QTc) interval \>470 ms (average of 3 tracings) on screening electrocardiogram (ECG)
    * Unstable angina pectoris
    * Congestive heart failure according to the New York Heart Association (NYHA) ≥ Grade 2)
    * Acute myocardial infarction
    * Conduction abnormality not controlled with pacemaker or medication
    * Significant ventricular or supraventricular arrhythmias. (Patients with chronic rate-controlled atrial fibrillation in the absence of other cardiac abnormalities are eligible.)
12. Inadequately controlled hypertension (ie, systolic blood pressure (SBP) \>180 mmHg or diastolic blood pressure (DBP) \>100 mmHg). Subjects with values above these levels must have their blood pressure (BP) controlled with medication prior to starting treatment.
13. Serious active infection at the time of treatment, or another serious underlying medical condition that that in the judgment of the investigator would impair the ability of the patient to receive protocol treatment.
14. HIV positive test within 8 weeks of screening. HIV positive patients with T-cell (CD4+) counts ≥350 cells/mL and not receiving treatment or does not plan to be treated with antiretroviral medication will be eligible for the study. Testing for seropositive status during screening will be at the discretion of the investigator in patients without previously reported results.
15. Active hepatitis B, or hepatitis C infection.

    * Patients will be tested for hepatitis C virus (HCV) and hepatitis B virus (HBV) at Screening.
    * Patients with hepatitis B (HepBsAg+) who have controlled infection (serum hepatitis B virus DNA level is below the limit of detection by PCR) may be enrolled into the study. Subjects with controlled infections must undergo periodic monitoring of HBV DNA per treating physician.
    * Patients with hepatitis C (HCV Ab+) who have controlled infection (undetectable HCV RNA by PCR either spontaneously or in response to a successful prior course of anti-HCV therapy) may be enrolled into the study. Patients with controlled infections must undergo periodic monitoring of HCV RNA per treating physician.
16. Presence of other active cancers, or history of treatment for invasive cancer ≤3 years. Patients with Stage I cancer who have received definitive local treatment and are considered unlikely to recur are eligible. All patients with previously treated in situ carcinoma (ie, non-invasive) are eligible, as are patients with history of non-melanoma skin cancer.
17. Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.
18. Routine use of corticosteroids or erythrocyte-stimulating factors as well as prophylactic use of colony-stimulating factors.
19. Use of any strong CYP3A4 inhibitor or strong inducer drugs ≤28 days or 5 half-lives (whichever is shorter) prior to the first dose of CPO-100. For CYP3A4 inducer drugs for which 5 half-lives is ≤28 days, a minimum of 14 days between discontinuation of the drug and administration of CPO-100 is required.
20. Use of herbal preparations/medications including, but are not limited to: St. John's wort, kava, ephedra (ma huang), gingko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto, and ginseng. A minimum of 14 days between discontinuation of the herbal preparation/medications and administration of CPO-100 is required.

Primary outcomes:
measure: Part A-1: Number of subjects with Dose Limiting Toxicities (DLTs)
timeFrame: At the end of cycle 1 (each cycle is 28 days)
measure: Part A-2: Number of subjects with Dose Limiting Toxicities (DLTs) when prophylactic use of G-CSF is allowed during Cycle 1
timeFrame: At the end of cycle 1 (each cycle is 28 days)
measure: Part B: Dose Expansion - Incidence and severity of Adverse Events
timeFrame: Screening to up to 4 years
Secondary outcomes:
measure: Area Under the Curve (AUC0-t) for CPO-100
timeFrame: 0, .5, 1, 2, 3, 4, 6, 8, 24, 48 and 72 hours (Day1) and Day 15
measure: Area Under the Curve (AUC0-∞) for CPO-100
timeFrame: 0, .5, 1, 2, 3, 4, 6, 8, 24, 48 and 72 hours (Day1)
measure: Cmax for CPO-100
timeFrame: 0, .5, 1, 2, 3, 4 6, 8, 24, 48 and 72 hours (Day 1) and Day 15
measure: Tmax for CPO-100
timeFrame: Time Frame: 0, .5, 1, 2, 3, 4 6, 8, 24, 48 and 72 hours (Day 1) and Day 15
measure: Overall response rate (ORR)
timeFrame: At the end of every 28 day cycle for up to 4 years
measure: Disease control rate (DCR)
timeFrame: At the end of every 28 day cycle for up to 4 years
measure: Duration of Response (DoR)
timeFrame: From first PR or CR until disease progression or death up to 4 years
measure: Progression-Free Survival (PSF)
timeFrame: From first dose until documented disease progression or death up to 4 years
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California Los Angeles
state: California
city: New Haven
country: United States
facility: Yale University School of Medicine - Yale Cancer Center
state: Connecticut
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Huntersville
country: United States
facility: Carolina BioOncology Institute
state: North Carolina
city: Lyndhurst
country: United States
facility: The Cleveland Clinic Foundation
state: Ohio
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Dallas
country: United States
facility: Texas Oncology - Baylor Charles A. Sammons Cancer Center
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialist
state: Virginia
Study officials:
affiliation: Conjupro Biotherapeutics, Inc.
name: Study Officials
role: STUDY_DIRECTOR
References:
citation: Aihara T, Kim Y, Takatsuka Y. Phase II study of weekly docetaxel in patients with metastatic breast cancer. Ann Oncol. 2002 Feb;13(2):286-92. doi: 10.1093/annonc/mdf027.
citation: Andre N, Carre M, Pasquier E. Metronomics: towards personalized chemotherapy? Nat Rev Clin Oncol. 2014 Jul;11(7):413-31. doi: 10.1038/nrclinonc.2014.89. Epub 2014 Jun 10.
citation: Aston WJ, Hope DE, Cook AM, Boon L, Dick I, Nowak AK, Lake RA, Lesterhuis WJ. Dexamethasone differentially depletes tumour and peripheral blood lymphocytes and can impact the efficacy of chemotherapy/checkpoint blockade combination treatment. Oncoimmunology. 2019 Jul 13;8(11):e1641390. doi: 10.1080/2162402X.2019.1641390. eCollection 2019.
citation: Bruno R, Olivares R, Berille J, Chaikin P, Vivier N, Hammershaimb L, Rhodes GR, Rigas JR. Alpha-1-acid glycoprotein as an independent predictor for treatment effects and a prognostic factor of survival in patients with non-small cell lung cancer treated with docetaxel. Clin Cancer Res. 2003 Mar;9(3):1077-82.
citation: de Wit R, de Bono J, Sternberg CN, Fizazi K, Tombal B, Wulfing C, Kramer G, Eymard JC, Bamias A, Carles J, Iacovelli R, Melichar B, Sverrisdottir A, Theodore C, Feyerabend S, Helissey C, Ozatilgan A, Geffriaud-Ricouard C, Castellano D; CARD Investigators. Cabazitaxel versus Abiraterone or Enzalutamide in Metastatic Prostate Cancer. N Engl J Med. 2019 Dec 26;381(26):2506-2518. doi: 10.1056/NEJMoa1911206. Epub 2019 Sep 30.
citation: Gradishar WJ. Taxanes for the treatment of metastatic breast cancer. Breast Cancer (Auckl). 2012;6:159-71. doi: 10.4137/BCBCR.S8205. Epub 2012 Oct 25.
citation: Hardin C, Shum E, Singh AP, Perez-Soler R, Cheng H. Emerging treatment using tubulin inhibitors in advanced non-small cell lung cancer. Expert Opin Pharmacother. 2017 May;18(7):701-716. doi: 10.1080/14656566.2017.1316374. Epub 2017 Apr 17.
citation: Harvey V, Mouridsen H, Semiglazov V, Jakobsen E, Voznyi E, Robinson BA, Groult V, Murawsky M, Cold S. Phase III trial comparing three doses of docetaxel for second-line treatment of advanced breast cancer. J Clin Oncol. 2006 Nov 1;24(31):4963-70. doi: 10.1200/JCO.2005.05.0294. Epub 2006 Oct 10.
citation: Minami H, Kawada K, Sasaki Y, Igarashi T, Saeki T, Tahara M, Itoh K, Fujii H. Pharmacokinetics and pharmacodynamics of protein-unbound docetaxel in cancer patients. Cancer Sci. 2006 Mar;97(3):235-41. doi: 10.1111/j.1349-7006.2006.00166.x.
citation: Ohbatake Y, Fushida S, Tsukada T, Kinoshita J, Oyama K, Hayashi H, Miyashita T, Tajima H, Takamura H, Ninomiya I, Yashiro M, Hirakawa K, Ohta T. Elevated alpha1-acid glycoprotein in gastric cancer patients inhibits the anticancer effects of paclitaxel, effects restored by co-administration of erythromycin. Clin Exp Med. 2016 Nov;16(4):585-592. doi: 10.1007/s10238-015-0387-9. Epub 2015 Sep 10.
citation: Palmeri L, Vaglica M, Palmeri S. Weekly docetaxel in the treatment of metastatic breast cancer. Ther Clin Risk Manag. 2008 Oct;4(5):1047-59. doi: 10.2147/tcrm.s3397.
citation: Scher HI, Morris MJ, Stadler WM, Higano C, Basch E, Fizazi K, Antonarakis ES, Beer TM, Carducci MA, Chi KN, Corn PG, de Bono JS, Dreicer R, George DJ, Heath EI, Hussain M, Kelly WK, Liu G, Logothetis C, Nanus D, Stein MN, Rathkopf DE, Slovin SF, Ryan CJ, Sartor O, Small EJ, Smith MR, Sternberg CN, Taplin ME, Wilding G, Nelson PS, Schwartz LH, Halabi S, Kantoff PW, Armstrong AJ; Prostate Cancer Clinical Trials Working Group 3. Trial Design and Objectives for Castration-Resistant Prostate Cancer: Updated Recommendations From the Prostate Cancer Clinical Trials Working Group 3. J Clin Oncol. 2016 Apr 20;34(12):1402-18. doi: 10.1200/JCO.2015.64.2702. Epub 2016 Feb 22.
citation: Socinski MA, Manikhas GM, Stroyakovsky DL, Makhson AN, Cheporov SV, Orlov SV, Yablonsky PK, Bhar P, Iglesias J. A dose finding study of weekly and every-3-week nab-Paclitaxel followed by carboplatin as first-line therapy in patients with advanced non-small cell lung cancer. J Thorac Oncol. 2010 Jun;5(6):852-61. doi: 10.1097/jto.0b013e3181d5e39e.
citation: Urien S, Barre J, Morin C, Paccaly A, Montay G, Tillement JP. Docetaxel serum protein binding with high affinity to alpha 1-acid glycoprotein. Invest New Drugs. 1996;14(2):147-51. doi: 10.1007/BF00210785.
citation: American Cancer Society. https://www.cancer.org/cancer/pancreatic-cancer/about/key-statistics.html Accessed 17 May 2022
citation: Deeken JF, Slack R, Weiss GJ, Ramanathan RK, Pishvaian MJ, Hwang J, Lewandowski K, Subramaniam D, He AR, Cotarla I, Rahman A, Marshall JL. A phase I study of liposomal-encapsulated docetaxel (LE-DT) in patients with advanced solid tumor malignancies. Cancer Chemother Pharmacol. 2013 Mar;71(3):627-33. doi: 10.1007/s00280-012-2048-y. Epub 2012 Dec 30.
citation: Eheman C, Henley SJ, Ballard-Barbash R, Jacobs EJ, Schymura MJ, Noone AM, Pan L, Anderson RN, Fulton JE, Kohler BA, Jemal A, Ward E, Plescia M, Ries LA, Edwards BK. Annual Report to the Nation on the status of cancer, 1975-2008, featuring cancers associated with excess weight and lack of sufficient physical activity. Cancer. 2012 May 1;118(9):2338-66. doi: 10.1002/cncr.27514. Epub 2012 Mar 28.
citation: NCCN Guidelines Version 1.2022, Management of Neutropenia
citation: Pronk LC. Modulation of docetaxel treatment [dissertation], Rotterdam: Erasmus Universiteit; 1997
citation: Simard EP, Ward EM, Siegel R, Jemal A. Cancers with increasing incidence trends in the United States: 1999 through 2008. CA Cancer J Clin. 2012 Mar-Apr;62(2):118-28. doi: 10.3322/caac.20141. Epub 2012 Jan 4.
citation: Smith BD, Smith GL, Hurria A, Hortobagyi GN, Buchholz TA. Future of cancer incidence in the United States: burdens upon an aging, changing nation. J Clin Oncol. 2009 Jun 10;27(17):2758-65. doi: 10.1200/JCO.2008.20.8983. Epub 2009 Apr 29.
citation: StatBite. U.S. pancreatic cancer rates. J Natl Cancer Inst. 2010 Dec 15;102(24):1822. doi: 10.1093/jnci/djq517. Epub 2010 Dec 7. No abstract available.
citation: Sweeney CJ, Chen YH, Carducci M, Liu G, Jarrard DF, Eisenberger M, Wong YN, Hahn N, Kohli M, Cooney MM, Dreicer R, Vogelzang NJ, Picus J, Shevrin D, Hussain M, Garcia JA, DiPaola RS. Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer. N Engl J Med. 2015 Aug 20;373(8):737-46. doi: 10.1056/NEJMoa1503747. Epub 2015 Aug 5.
citation: Taxotere® US Package Insert (version 11/2021)
citation: Von Hoff DD, Ramanathan RK, Borad MJ, Laheru DA, Smith LS, Wood TE, Korn RL, Desai N, Trieu V, Iglesias JL, Zhang H, Soon-Shiong P, Shi T, Rajeshkumar NV, Maitra A, Hidalgo M. Gemcitabine plus nab-paclitaxel is an active regimen in patients with advanced pancreatic cancer: a phase I/II trial. J Clin Oncol. 2011 Dec 1;29(34):4548-54. doi: 10.1200/JCO.2011.36.5742. Epub 2011 Oct 3.
citation: Von Hoff DD, Ervin T, Arena FP, Chiorean EG, Infante J, Moore M, Seay T, Tjulandin SA, Ma WW, Saleh MN, Harris M, Reni M, Dowden S, Laheru D, Bahary N, Ramanathan RK, Tabernero J, Hidalgo M, Goldstein D, Van Cutsem E, Wei X, Iglesias J, Renschler MF. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013 Oct 31;369(18):1691-703. doi: 10.1056/NEJMoa1304369. Epub 2013 Oct 16.
citation: Worni M, Guller U, White RR, Castleberry AW, Pietrobon R, Cerny T, Gloor B, Koeberle D. Modest improvement in overall survival for patients with metastatic pancreatic cancer: a trend analysis using the surveillance, epidemiology, and end results registry from 1988 to 2008. Pancreas. 2013 Oct;42(7):1157-63. doi: 10.1097/MPA.0b013e318291fbc5.