Sandostatin LAR and Axitinib vs Pbo in Pnts With Advanced Well-differentiated Non-pancreatic Neuroendocrine Carcinomas

NCT01744249

Last updated date
Study Location
Marburg Universitätsklinikum Giessen und Marburg GmbH
Marburg, , 35043, Germany
Contact
1-800-718-1021

FOR MORE INFORMATION

Contact a representative by phone, email, or visiting the study website. Please see the references below:

By phone

Pfizer Clinical Trials Contact Center

1-800-718-1021

By email

Contact

[email protected]

Call Now

Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Neuroendocrine Tumors, Advanced Cancer
Sex
Females and Males
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
18 + years
Inclusion Criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

1. G1-G2 neuroendocrine tumor (WHO 2010) of histologically confirmed non-pancreatic origin, functioning and nonfunctioning

2. Metastatic or locally advanced disease not amenable to treatment with curative intent

3. Clinical and/or radiological disease progression documented in the 12 months prior to study entry.

4. Patients should have at least one measurable lesion as defined by RECIST 1.1 criteria. Patients should not have undergone local or regional ablative procedures (embolization, cryoablation, radiofrequency ablation, or others) in the 6 months prior to entering the study, unless there are other locations of measurable disease or clear radiological progression after carrying out these procedures (in these cases, local and regional ablation procedures shall be permitted if they have been performed at least 1 month prior to enrollment in the study).

5. Ki-67 < 20%

6. Prior treatment with somatostatin analogues is allowed

7. Prior treatment with interferon is allowed

8. Prior treatment is allowed with up to 2 antineoplastic systemic treatment lines different from SAs or IFN (systemic treatment is understood as conventional cytotoxic chemotherapy or new drugs for therapeutic targets as mTOR or other, as long as it is not directed against VEGF/VEGFR). Treatment with SAs or IFN does not count as prior lines of antineoplastic treatment.

9. Prior treatment with targeted therapy against VEGF or VEGFR is not allowed.

10. Adequate organ function as defined by the following criteria:

- Absolute neutrophil count ≥ 1500 cells/mm3,

- Platelet count ≥ 75,000 cells/mm3,

- Hemoglobin ≥ 9.0 g/dL,

- AST y ALT ≤ 2.5 x upper limit of normal (ULN), except if liver metastases exist, in which case AST and ALT 5.0 ≤ x ULN is allowed,

- Total bilirubin ≤ 1.5 x ULN,

- Serum creatinine ≤ 1.5 x ULN or calculated creatinine clearance ≥ 60 mL/min,

- Proteinuria < 2+ by reactive strip. If the reactive strip is ≥ 2+, a 24-hour urine sample should be collected and the patient may be eligible if urinary protein excretion is < 2 g every 24 hours.

11. Men or women aged ≥ 18 years.

12. ECOG performance status 0-2

13. Life expectancy ≥ 12 weeks

14. At least 4 weeks should pass from the end of the previous systemic treatment with resolution of all treatment-related toxicities to grade ≤ 1 according to NCI CTCAE Version 4.0 or to baseline, except for alopecia or properly treated hypothyroidism.

15. No prior evidence of uncontrolled hypertension should exist, as documented by 2 baseline blood pressure readings taken at least 1 hour apart. Baseline readings of systolic blood pressure should be ≤ 150 mm Hg and baseline readings of diastolic pressure should be ≤ 90 mm Hg. Patients whose hypertension is being controlled with antihypertensive therapy are eligible.

16. Women (or their partners) should be surgically sterilized or postmenopausal, or must agree to use an effective contraceptive method during and for at least 6 months after receiving study treatment. All women of childbearing age should have a negative pregnancy test (serum/urine) within 7 days prior to starting treatment. Men (or their partners) should be surgically sterilized or must agree to use an effective contraceptive method during and for at least 6 months after receiving study treatment. The definition of an effective contraceptive method must comply with local regulations and will be based on the criterion of the principal investigator or a designated associate. Lactating women may not participate in this study.

17. Signed and dated informed consent document stating that the patient has been informed of all the pertinent aspects of the trial prior to recruitment.

18. Willingness and ability to comply with scheduled visits, treatment plans (including willingness to take axitinib or placebo according to randomization), laboratory tests, and other study procedures.

Exclusion Criteria
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details


1. Subjects must be evaluated with regard to the following exclusion criteria:


1. The following types of endocrine tumors will not be included: paraganglioma, adrenal
endocrine tumor, thyroid, parathyroid, or pituitary.


2. Major surgery within previous 4 weeks, or radiation therapy within 2 weeks prior to
the start of treatment. Prior palliative radiotherapy for metastatic lesions is
permitted if there is at least one measurable lesion that has not been irradiated
(i.e., if there are other non-irradiated target lesions).


3. Gastrointestinal abnormalities, including:


- Inability to swallow oral medication;


- Need for intravenous feeding;


- Prior surgical procedures that affect absorption, including total gastric
resection;


- Treatment for active peptic ulcer in the last 6 months;


- Uncontrolled active gastrointestinal bleeding unrelated to cancer, as evidenced
by hematemesis, hematochezia or clinically significant melena in the last 3
months without evidence of resolution documented by endoscopy or colonoscopy;


- Malabsorption syndromes;


4. Current or anticipated need for treatment with drugs that are potent inhibitors of
CYP3A4 (grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole,
erythromycin, telithromycin, clarithromycin, indinavir, saquinavir, ritonavir,
nelfinavir, lopinavir, atazanavir, amprenavir, fosamprenavir, and delavirdine) unless
they can be replaced by another medication with minimal potential for CYP3A4/5
inhibition. The use of low-dose oral steroids (< 5 mg/day prednisone or equivalent) is
allowed. Co-administration of steroids may increase plasma concentrations of axitinib.


5. Current use or anticipated need for treatment with drugs that are known potent
CYP3A4/5 inducers (carbamazepine, dexamethasone, felbamate, phenobarbital, phenytoin,
amobarbital, nevirapine, primidone, rifabutin, rifampicin, and St. John's wort) unless
they can be replaced by another medication with minimal potential for CYP3A4
induction. Co-administration of CYP3A4/5 inducers may decrease plasma concentrations
of axitinib.


6. Need for anticoagulant therapy with oral vitamin K antagonists. Low doses of
anticoagulants to maintain the patency of a central venous access device or to prevent
deep vein thrombosis are permitted. Use with therapeutic doses of low molecular weight
heparin is allowed.


7. Clinically relevant history of bleeding in the last 6 months, including severe
hemoptysis or hematuria, unless it has been due to a treated cause (e.g., completely
resected bleeding intestinal tumor).


8. Active epilepsy or evidence of brain metastases, spinal cord compression, or
carcinomatous meningitis.


9. Serious uncontrolled illness or active infections that may interfere with the
patient's ability to receive the study treatment.


10. Any of the following events in the 12 months prior to administration of the study
drug: myocardial infarction, uncontrolled angina, implantation of a coronary or
peripheral bypass, symptomatic congestive heart failure, stroke or transient ischemic
attack. Deep vein thrombosis or pulmonary embolism in the prior 6 months.


11. Ongoing grade ≥ 2 cardiac arrhythmias according to NCI CTCAE: atrial fibrillation of
any grade or QTc interval > 450 ms for men or > 470 ms for women.


12. Patients with human immunodeficiency virus (HIV) infection or acquired
immunodeficiency syndrome-related disease.


13. Prior history of cancer except those treated with curative intent for non-melanoma
skin cancer in situ, breast or cervical cancer in situ, or those treated for any
cancer with curative intent and no evidence of disease in the last 5 years prior to
enrollment in the study.


14. Dementia or significantly altered mental status that could prevent compression, or
submission of informed consent and compliance with the requirements of this protocol.


15. Any severe, acute or chronic medical or psychiatric condition, or laboratory
abnormality that may increase the risk associated with participation in the study or
with study drug administration, or that may interfere with the interpretation of
results, and that could interfere with the patient's ability to take part in this
study in the investigator's opinion.


16. The patient's participation or intention to participate (in the 4 weeks prior to
starting drug administration) in a study in which the patient will receive an
investigational medicinal product.


17. Subjects who are institutionalized by governmental or by judicial decision, or
subjects who are dependent of the sponsor, the investigator or the trial site will be
excluded from participation.

NEED INFO?

Questions about a trial? Call or email to reach a Pfizer Clinical Trial Contact Center Representative

Pfizer Clinical Trials Contact Center

1-800-718-1021

[email protected]

TRY A NEW SEARCH

Search for Clinical Trials by condition, keyword or trial number. Share your location or enter your city or zip code to find studies near you.

Based on your search, you may also be interested in

Neuroendocrine Tumors, Advanced CancerSandostatin LAR and Axitinib vs Pbo in Pnts With Advanced Well-differentiated Non-pancreatic Neuroendocrine Carcinomas
NCT01744249
  1. Marburg,
  2. München,
  3. Perugia,
  4. Birmingham,
  5. London,
  6. Granada,
  7. Zaragoza,
  8. Rome,
  9. Oviedo, Asturias
  10. L'Hospitalet de Llobregat, Barcelona
  11. Santander,
  12. San Sebastian,
  13. Málaga, Malaga
  14. Barcelona,
  15. Madrid,
  16. Vigo, Pontevedra
  17. Manchester,
  18. Madrid,
  19. Madrid,
  20. Salamanca,
  21. Valencia,
  22. Madrid,
  23. Berlin,
  24. Madrid,
  25. Burgos,
  26. Sevilla,
  27. A Coruña,
  28. Madrid,
ALL GENDERS
18 Years+
years
MULTIPLE SITES
Advanced Information
Descriptive Information
Brief Title  ICMJE Sandostatin LAR and Axitinib vs Pbo in Pnts With Advanced Well-differentiated Non-pancreatic Neuroendocrine Carcinomas
Official Title  ICMJE A Phase II/III Randomized Double-blind Study of Sandostatin LAR in Combination With Axitinib Versus Sandostatin LAR With Placebo in Patients With Advanced G1-G2 Neuroendocrine Tumours (WHO 2010) of Non-pancreatic Origin
Brief Summary Assess whether therapy with axitinib, a potent angiogenic inhibitor of the tyrosine kinase receptors of VEGF bioavailable by oral administration, is capable of improving PFS in patients with advanced G1-G2 NETs of nonpancreatic origin with progressive disease documented in the 12 months prior to entering the study.
Detailed Description Phase II/III, prospective, multicenter, randomized (1:1), double-blind study to evaluate the efficacy and tolerability of axitinib in patients diagnosed with advanced G1-G2 neuroendocrine tumors (WHO 2010) of nonpancreatic origin that have presented documented disease progression in the 12 months prior to entering the study. In the first part of the study (Phase II), 105 patients were enrolled. The second part of the study is the expansion to Phase III, which is expected to include 148 additional patients. Patients will be randomized to receive Sandostatin LAR with axitinib or Sandostatin LAR with placebo until disease progression or unacceptable toxicity occurs. Randomization will be stratified by the time from diagnosis to enrollment in the study (more vs less than or equal to 12 months), the origin of the primary tumor (gastrointestinal tract vs non-gastrointestinal tract [lung or other sites]) and ki-67 (< 5% vs > 5%).
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Neuroendocrine Tumors
  • Advanced Cancer
Intervention  ICMJE
  • Drug: Axitinib
    Orally, 5mg, twice daily, until progression or until unacceptable toxicity, with or without food intake.
  • Drug: Sandostatin LAR
    Intramuscular, 30mg, single injection every 28 days, until disease progression or unacceptable toxicity
  • Drug: Placebo
    orally, twice daily, until disease progression or unacceptable toxicity, with or without food intake.
Study Arms  ICMJE
  • Experimental: Axitinib + Sandostatin LAR
    Axitinib 5 mg BID + Sandostatin LAR 30mg/28 days
    Interventions:
    • Drug: Axitinib
    • Drug: Sandostatin LAR
  • Placebo Comparator: Placebo + Sandostatin LAR
    Placebo BID + Sandostatin LAR 30mg/28 days
    Interventions:
    • Drug: Sandostatin LAR
    • Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: October 21, 2019)
255
Original Estimated Enrollment  ICMJE
 (submitted: December 5, 2012)
80
Estimated Study Completion Date  ICMJE October 2021
Estimated Primary Completion Date November 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. G1-G2 neuroendocrine tumor (WHO 2010) of histologically confirmed non-pancreatic origin, functioning and nonfunctioning
  2. Metastatic or locally advanced disease not amenable to treatment with curative intent
  3. Clinical and/or radiological disease progression documented in the 12 months prior to study entry.
  4. Patients should have at least one measurable lesion as defined by RECIST 1.1 criteria. Patients should not have undergone local or regional ablative procedures (embolization, cryoablation, radiofrequency ablation, or others) in the 6 months prior to entering the study, unless there are other locations of measurable disease or clear radiological progression after carrying out these procedures (in these cases, local and regional ablation procedures shall be permitted if they have been performed at least 1 month prior to enrollment in the study).
  5. Ki-67 < 20%
  6. Prior treatment with somatostatin analogues is allowed
  7. Prior treatment with interferon is allowed
  8. Prior treatment is allowed with up to 2 antineoplastic systemic treatment lines different from SAs or IFN (systemic treatment is understood as conventional cytotoxic chemotherapy or new drugs for therapeutic targets as mTOR or other, as long as it is not directed against VEGF/VEGFR). Treatment with SAs or IFN does not count as prior lines of antineoplastic treatment.
  9. Prior treatment with targeted therapy against VEGF or VEGFR is not allowed.
  10. Adequate organ function as defined by the following criteria:

    • Absolute neutrophil count ? 1500 cells/mm3,
    • Platelet count ? 75,000 cells/mm3,
    • Hemoglobin ? 9.0 g/dL,
    • AST y ALT ? 2.5 x upper limit of normal (ULN), except if liver metastases exist, in which case AST and ALT 5.0 ? x ULN is allowed,
    • Total bilirubin ? 1.5 x ULN,
    • Serum creatinine ? 1.5 x ULN or calculated creatinine clearance ? 60 mL/min,
    • Proteinuria < 2+ by reactive strip. If the reactive strip is ? 2+, a 24-hour urine sample should be collected and the patient may be eligible if urinary protein excretion is < 2 g every 24 hours.
  11. Men or women aged ? 18 years.
  12. ECOG performance status 0-2
  13. Life expectancy ? 12 weeks
  14. At least 4 weeks should pass from the end of the previous systemic treatment with resolution of all treatment-related toxicities to grade ? 1 according to NCI CTCAE Version 4.0 or to baseline, except for alopecia or properly treated hypothyroidism.
  15. No prior evidence of uncontrolled hypertension should exist, as documented by 2 baseline blood pressure readings taken at least 1 hour apart. Baseline readings of systolic blood pressure should be ? 150 mm Hg and baseline readings of diastolic pressure should be ? 90 mm Hg. Patients whose hypertension is being controlled with antihypertensive therapy are eligible.
  16. Women (or their partners) should be surgically sterilized or postmenopausal, or must agree to use an effective contraceptive method during and for at least 6 months after receiving study treatment. All women of childbearing age should have a negative pregnancy test (serum/urine) within 7 days prior to starting treatment. Men (or their partners) should be surgically sterilized or must agree to use an effective contraceptive method during and for at least 6 months after receiving study treatment. The definition of an effective contraceptive method must comply with local regulations and will be based on the criterion of the principal investigator or a designated associate. Lactating women may not participate in this study.
  17. Signed and dated informed consent document stating that the patient has been informed of all the pertinent aspects of the trial prior to recruitment.
  18. Willingness and ability to comply with scheduled visits, treatment plans (including willingness to take axitinib or placebo according to randomization), laboratory tests, and other study procedures.

Exclusion Criteria:

1. Subjects must be evaluated with regard to the following exclusion criteria:

  1. The following types of endocrine tumors will not be included: paraganglioma, adrenal endocrine tumor, thyroid, parathyroid, or pituitary.
  2. Major surgery within previous 4 weeks, or radiation therapy within 2 weeks prior to the start of treatment. Prior palliative radiotherapy for metastatic lesions is permitted if there is at least one measurable lesion that has not been irradiated (i.e., if there are other non-irradiated target lesions).
  3. Gastrointestinal abnormalities, including:

    • Inability to swallow oral medication;
    • Need for intravenous feeding;
    • Prior surgical procedures that affect absorption, including total gastric resection;
    • Treatment for active peptic ulcer in the last 6 months;
    • Uncontrolled active gastrointestinal bleeding unrelated to cancer, as evidenced by hematemesis, hematochezia or clinically significant melena in the last 3 months without evidence of resolution documented by endoscopy or colonoscopy;
    • Malabsorption syndromes;
  4. Current or anticipated need for treatment with drugs that are potent inhibitors of CYP3A4 (grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole, erythromycin, telithromycin, clarithromycin, indinavir, saquinavir, ritonavir, nelfinavir, lopinavir, atazanavir, amprenavir, fosamprenavir, and delavirdine) unless they can be replaced by another medication with minimal potential for CYP3A4/5 inhibition. The use of low-dose oral steroids (< 5 mg/day prednisone or equivalent) is allowed. Co-administration of steroids may increase plasma concentrations of axitinib.
  5. Current use or anticipated need for treatment with drugs that are known potent CYP3A4/5 inducers (carbamazepine, dexamethasone, felbamate, phenobarbital, phenytoin, amobarbital, nevirapine, primidone, rifabutin, rifampicin, and St. John's wort) unless they can be replaced by another medication with minimal potential for CYP3A4 induction. Co-administration of CYP3A4/5 inducers may decrease plasma concentrations of axitinib.
  6. Need for anticoagulant therapy with oral vitamin K antagonists. Low doses of anticoagulants to maintain the patency of a central venous access device or to prevent deep vein thrombosis are permitted. Use with therapeutic doses of low molecular weight heparin is allowed.
  7. Clinically relevant history of bleeding in the last 6 months, including severe hemoptysis or hematuria, unless it has been due to a treated cause (e.g., completely resected bleeding intestinal tumor).
  8. Active epilepsy or evidence of brain metastases, spinal cord compression, or carcinomatous meningitis.
  9. Serious uncontrolled illness or active infections that may interfere with the patient's ability to receive the study treatment.
  10. Any of the following events in the 12 months prior to administration of the study drug: myocardial infarction, uncontrolled angina, implantation of a coronary or peripheral bypass, symptomatic congestive heart failure, stroke or transient ischemic attack. Deep vein thrombosis or pulmonary embolism in the prior 6 months.
  11. Ongoing grade ? 2 cardiac arrhythmias according to NCI CTCAE: atrial fibrillation of any grade or QTc interval > 450 ms for men or > 470 ms for women.
  12. Patients with human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome-related disease.
  13. Prior history of cancer except those treated with curative intent for non-melanoma skin cancer in situ, breast or cervical cancer in situ, or those treated for any cancer with curative intent and no evidence of disease in the last 5 years prior to enrollment in the study.
  14. Dementia or significantly altered mental status that could prevent compression, or submission of informed consent and compliance with the requirements of this protocol.
  15. Any severe, acute or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with participation in the study or with study drug administration, or that may interfere with the interpretation of results, and that could interfere with the patient's ability to take part in this study in the investigator's opinion.
  16. The patient's participation or intention to participate (in the 4 weeks prior to starting drug administration) in a study in which the patient will receive an investigational medicinal product.
  17. Subjects who are institutionalized by governmental or by judicial decision, or subjects who are dependent of the sponsor, the investigator or the trial site will be excluded from participation.
Sex/Gender  ICMJE
Sexes Eligible for Study:All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany,   Italy,   Spain,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01744249
Other Study ID Numbers  ICMJE AXI-IIG-02
2011-001550-29 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Grupo Espanol de Tumores Neuroendocrinos
Study Sponsor  ICMJE Grupo Espanol de Tumores Neuroendocrinos
Collaborators  ICMJE Pfizer
Investigators  ICMJE
Study Chair:Rocio Garcia Carbonero, MDHospital 12 de Octubre
PRS Account Grupo Espanol de Tumores Neuroendocrinos
Verification Date October 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP