Metronomic Chemotherapy in Patients With Advanced Solid Tumor With Bone Metastasis and Advanced Pretreated Osteosarcoma

NCT02517918

Last updated date
Study Location
Centre Oscar Lambret
Lille, , 59000, France
Contact
+33 (0)556333333

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

1. Histology:

- Advanced solid tumor with radiologically proven bone metastasis, (dose escalation part)

- Patients with osteogenic osteosarcoma (dose escalation part and expansion cohort) histologically confirmed by central review

2. Metastatic or unresectable locally advanced disease, not eligible for alternative local treatment (radiotherapy for instance)

3. Age > 18 years for patients with solid tumor and ≥ 13 years for patients with osteosarcoma

4. ECOG, performance status ≤ 1

5. Life expectancy > 3 months

6. Measurable disease according to RECIST v1.1. At least one site of disease must be uni-dimensionally ≥ 10 mm

7. Patients must have histologically confirmed diagnosis of locally advanced and/or metastatic solid tumors, which are not amenable to standard treatment, including for patients with osteosarcoma conventional agents such as anthracyclines, platinum salts, ifosfamide and/or methotrexate

8. At least three weeks since last chemotherapy, immunotherapy or any other pharmacological treatment and/or radiotherapy

9. Adequate haematological, renal, metabolic and hepatic function:

- Haemoglobin ≥ 10 g/dl (patients may have received prior red blood cell transfusion, if clinically indicated); leucocytes ≥ 3 x 10^9/l, absolute neutrophil count ≥ 1.5 x 10^9/l, and platelet count ≥ 120 x 10^9/l.

- Alanine aminotransferase and aspartate aminotransferase ≤ 2.5 x upper limit of normality (ULN)

- Total bilirubin ≤ 1.5 x ULN

- Calculated creatinine clearance > 40 ml/min/1.73 m² (according to MDRD formula)

- Creatine phosphokinase ≤ 2.5 x ULN

- Albumin > 25 g/l

10. No prior or concurrent malignant disease diagnosed or treated in the last 2 years except adequately treated in situ carcinoma of the cervix, basal or squamous skin cell carcinoma, or in situ transitional bladder cell carcinoma,

11. Recovery to grade ≤ 1 from any adverse event derived from previous treatment (excluding alopecia of any grade and non-painful peripheral neuropathy grade ≤ 2) according to the NCI-CTCAE, version 4

12. Patients with a French social security in compliance with the French law relating to biomedical research

13. Voluntarily signed and dated written informed consent prior to any study specific procedure

14. Women of childbearing potential must have a negative serum pregnancy test before study entry. Both women and men must agree to use a medically acceptable method of contraception throughout the treatment period and for six months after discontinuation of treatment

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


1. Previous treatment with sirolimus


2. Concomitant diseases/conditions:


- Clinically significant and/or rapidly accumulating ascites, pericardial and/or
pleural effusions


- Unstable cardiac disease, pulse oximetry saturation < 90% at rest


- Clinically significant immunodeficiency, such as HIV or active Hepatitis B or C


- History of auto-immune disease, transplantation


3. Central nervous system malignancy


4. Men or women of childbearing potential who are not using an effective method of
contraception; women who are pregnant or breast feeding


5. Patients receiving any substances that are inhibitors or inducers of CYP450 3A4


6. Ongoing or recent (<6 weeks) dental problem, including any severe tooth or jaw
infection (mandible and maxilla), dental trauma, dental or stomatological surgery
(implants). Current dental cares are allowed


7. History of maxillary osteonecrosis or delayed healing after dental surgery


8. Participation to a study involving a medical or therapeutic intervention in the last
30 days


9. Previous enrolment in the present study


10. Patient unable to follow and comply with the study procedures because of any
geographical, familial, social or psychological reasons


11. Known hypersensitivity to any involved study drug or any of its formulation components


12. Patients receiving live vaccines within 30 days prior to the first dose of study
therapy and while participating in study

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Solid Tumor, OsteosarcomaMetronomic Chemotherapy in Patients With Advanced Solid Tumor With Bone Metastasis and Advanced Pretreated Osteosarcoma
NCT02517918
  1. Lille,
  2. Bordeaux,
  3. Lyon,
ALL GENDERS
13 Years+
years
MULTIPLE SITES
Advanced Information
Descriptive Information
Brief Title  ICMJE Metronomic Chemotherapy in Patients With Advanced Solid Tumor With Bone Metastasis and Advanced Pretreated Osteosarcoma
Official Title  ICMJE Metronomic Cyclophosphamide and Methotrexate Combined With Zoledronic Acid and Sirolimus in Patients With Advanced Solid Tumor With Bone Metastasis and Advanced Pretreated Osteosarcoma. A Phase Ib Study From the French Sarcoma Group
Brief Summary This is a prospective open-labeled phase I trial based on a dose escalating study design assessing two dose levels of sirolimus when prescribed in combination with metronomic cyclophosphamide (CP), methotrexate (MT) and zoledronic acid (ZA) followed by an expansion cohort once the Maximum Tolerated Dose (MTD) is established.
Detailed Description

The dose escalation part of the trial will be concerned on adults with advanced solid tumor with bone metastasis and young and adult patients with unresectable locally advanced or metastatic osteosarcoma.

The Expansion cohort will be conducted on young and adult patients with unresectable locally advanced or metastatic osteosarcoma.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Solid Tumor
  • Osteosarcoma
Intervention  ICMJE Drug: Sirolimus combined with CP, MT and ZA

Cyclophosphamide, Methotrexate and Sirolimus will be administrated orally. Zoledronic Acid will be administrated by infusion (IV).

Trial based on a dose escalating study design assessing two dose levels of sirolimus when prescribed in combination with metronomic cyclophosphamide (CP), methotrexate (MT) and zoledronic acid (ZA) followed by an expansion cohort once the MTD is established.

Other Name: Endoxan, Methotrexate, Rapamune, Zoledronic acid
Study Arms  ICMJE Experimental: Sirolimus combined with CP, MT and ZA
Drug : Metronomic Cyclophosphamide, Methotrexate, Sirolimus, Zoledronic acid Assessment of the maximum tolerated dose of sirolimus Cyclophosphamide, Methotrexate and Sirolimus will be administrated orally. Zoledronic Acid will be administrated by infusion (IV).
Intervention: Drug: Sirolimus combined with CP, MT and ZA
Publications * Hattinger CM, Patrizio MP, Magagnoli F, Luppi S, Serra M. An update on emerging drugs in osteosarcoma: towards tailored therapies? Expert Opin Emerg Drugs. 2019 Sep;24(3):153-171. doi: 10.1080/14728214.2019.1654455. Epub 2019 Aug 14. Review.

*   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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 4, 2015)
26
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 2021
Estimated Primary Completion Date January 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Histology:

    • Advanced solid tumor with radiologically proven bone metastasis, (dose escalation part)
    • Patients with osteogenic osteosarcoma (dose escalation part and expansion cohort) histologically confirmed by central review
  2. Metastatic or unresectable locally advanced disease, not eligible for alternative local treatment (radiotherapy for instance)
  3. Age > 18 years for patients with solid tumor and ? 13 years for patients with osteosarcoma
  4. ECOG, performance status ? 1
  5. Life expectancy > 3 months
  6. Measurable disease according to RECIST v1.1. At least one site of disease must be uni-dimensionally ? 10 mm
  7. Patients must have histologically confirmed diagnosis of locally advanced and/or metastatic solid tumors, which are not amenable to standard treatment, including for patients with osteosarcoma conventional agents such as anthracyclines, platinum salts, ifosfamide and/or methotrexate
  8. At least three weeks since last chemotherapy, immunotherapy or any other pharmacological treatment and/or radiotherapy
  9. Adequate haematological, renal, metabolic and hepatic function:

    • Haemoglobin ? 10 g/dl (patients may have received prior red blood cell transfusion, if clinically indicated); leucocytes ? 3 x 10^9/l, absolute neutrophil count ? 1.5 x 10^9/l, and platelet count ? 120 x 10^9/l.
    • Alanine aminotransferase and aspartate aminotransferase ? 2.5 x upper limit of normality (ULN)
    • Total bilirubin ? 1.5 x ULN
    • Calculated creatinine clearance > 40 ml/min/1.73 m² (according to MDRD formula)
    • Creatine phosphokinase ? 2.5 x ULN
    • Albumin > 25 g/l
  10. No prior or concurrent malignant disease diagnosed or treated in the last 2 years except adequately treated in situ carcinoma of the cervix, basal or squamous skin cell carcinoma, or in situ transitional bladder cell carcinoma,
  11. Recovery to grade ? 1 from any adverse event derived from previous treatment (excluding alopecia of any grade and non-painful peripheral neuropathy grade ? 2) according to the NCI-CTCAE, version 4
  12. Patients with a French social security in compliance with the French law relating to biomedical research
  13. Voluntarily signed and dated written informed consent prior to any study specific procedure
  14. Women of childbearing potential must have a negative serum pregnancy test before study entry. Both women and men must agree to use a medically acceptable method of contraception throughout the treatment period and for six months after discontinuation of treatment

Exclusion Criteria:

  1. Previous treatment with sirolimus
  2. Concomitant diseases/conditions:

    • Clinically significant and/or rapidly accumulating ascites, pericardial and/or pleural effusions
    • Unstable cardiac disease, pulse oximetry saturation < 90% at rest
    • Clinically significant immunodeficiency, such as HIV or active Hepatitis B or C
    • History of auto-immune disease, transplantation
  3. Central nervous system malignancy
  4. Men or women of childbearing potential who are not using an effective method of contraception; women who are pregnant or breast feeding
  5. Patients receiving any substances that are inhibitors or inducers of CYP450 3A4
  6. Ongoing or recent (<6 weeks) dental problem, including any severe tooth or jaw infection (mandible and maxilla), dental trauma, dental or stomatological surgery (implants). Current dental cares are allowed
  7. History of maxillary osteonecrosis or delayed healing after dental surgery
  8. Participation to a study involving a medical or therapeutic intervention in the last 30 days
  9. Previous enrolment in the present study
  10. Patient unable to follow and comply with the study procedures because of any geographical, familial, social or psychological reasons
  11. Known hypersensitivity to any involved study drug or any of its formulation components
  12. Patients receiving live vaccines within 30 days prior to the first dose of study therapy and while participating in study
Sex/Gender  ICMJE
Sexes Eligible for Study:All
Ages  ICMJE 13 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Maud TOULMONDE, Doctor+33 (0)556333333[email protected]
Contact: Simone MATHOULIN-PELISSIER, Professor+33 (0)556333333[email protected]
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02517918
Other Study ID Numbers  ICMJE IB 2014-01
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Institut Bergonié
Study Sponsor  ICMJE Institut Bergonié
Collaborators  ICMJE
  • Reliable Cancer Therapies
  • Pfizer
Investigators  ICMJE
Study Chair:Maud TOULMONDE, DoctorInstitut Bergonié
PRS Account Institut Bergonié
Verification Date February 2020

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