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Study Summary
No. 2008-0646:.......Advanced Cancers......Razelle Kurzrock......Investigational Cancer Therapeutics
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Study Summary Title
Study Summary
Number:
2008-0646
Study Title:Phase Ib Study to Evaluate the Safety of Combining IGF-1R Antagonist R1507 with Multiple Standard Chemotherapy Drug Treatments in Patients with Advanced Malignancies
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Physician New Patient Referral
Name:Razelle KurzrockPatients Call:800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Dept:Investigational Cancer TherapeuticsReferring MD
Call:
800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Phone:713-563-1930
Contact us about clinical trials
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General Information
Disease Group:Advanced CancersSupported By:Hoffman-LaRoche
Phase of Study:Phase IReturn
Visit:
Patients will return to the clinic on a weekly basis.
Treatment
Agents:
5-Fluorouracil
Bevacizumab
Capecitabine
Carboplatin
Cetuximab
Docetaxel
Erlotinib
Etoposide
Folic Acid
Gemcitabine
Irinotecan
Oxaliplatin
Paclitaxel
Pemetrexed
R1507
Sorafenib
Temozolomide
Trastuzumab
Home Care:N/A
Treatment Loc:Both at MDACC & outside MDACC at one or more Collaborating Sites or Institutions
Estimated
Length of Stay
in Houston:
N/A
Description/
Intervention:
The goal of this clinical research study is to learn if the study drug, R1507,
is safe and tolerable when given in combination with 12 different standard
chemotherapy combinations.

In this study group, R1507 will be given with the drugs Gemzar (gemcitabine)
and Tarceva (erlotinib hydrochloride).
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Study Objectives / Outcomes
Primary Objective
To establish the saftey and tolerability of R1507 given at a biologically active maximally administered monotherapy dose and in combination with multiple standard chemotherapy drug combinations.

Secondary Objectives
  • To explore potential differential effect of chemotherapy regimens on trough levels of R1507
  • To describe the safety, tolerability, and pharmacokinetics of R1507 with the 27 mg/kg q3W monotherapy dose schedule
  • To explore changes in serum and tumor pharmacodynamic markers following administratino of R1507 monotherapy and incombination with standard chemotherapy treatment regimens

Exploratory Objective
To describe any anti-tumor response and progression free survival of R1507 administered with standard chemotherapy treatments.
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Study Status Information
Study Activation / Registration Date:01/29/2009
IRB Review and Approval Date:01/29/2009
Study Type:Phase I
Recruitment Status:Terminated
Projected Accrual:252
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Enrollment Eligibility
If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:1) Age >/= 18 years of age.

2) Patients must have histologically or cytologically confirmed malignant neoplasms (not including leukemias) untreated or previously treated requiring further treatment.

3) Patients must have failed prior standard curative chemotherapy for their disease OR the proposed chemotherapy regimen to which R1507 is added represents an acceptable standard treatment for their disease.

4) Able to comply with the protocol

5) Life expectancy of >/= 8 weeks

6) ECOG Performance Status of 0 or 1

7) INR </= 1.5 (or PT </= 1.5 X ULN) and PTT </= 1.5 x ULN

8) Adequate bone marrow function as evidenced by: absolute neutrophil count >/= 1,500/microliter; platelet count >/= 100,000/microliter; hemoglobin >/= 9.0 g/dL

9) Adequate renal function as evidenced by serum creatinine </= 2.0 mg/dL

10) Adequate hepatic function as evidenced by: serum albumin >/= 2.5 mg/dL; serum total bilirubin </= 2.0 mg/dL; AST and ALT </= 2.5 x ULN for the reference lab (</= 5 x ULN for patients with known hepatic metastases)

11) HbA1c </= 7%

12) Negative pregnancy test within 7 days of starting study treatment in pre-menopausal women and women < 2 years after the onset of menopause.

13) Patients or their legal representatives must be able to understand and provide written informed consent to participate in the trial.

Exclusion Criteria:1) ALL PATIENTS Prior treatment with an agent targeting the IGF-1R pathway

2) Chemotherapy within 2 weeks of start of therapy

3) Patients who have not recovered to </= grade 1 from any toxic effects of previously administered therapies

4) Prior irradiation within the last 4 weeks prior to the start of therapy

5) Patients who have known hypersensitivity to any of the components of R1507 or who have had prior hypersensitivity reactions to monoclonal antibodies or to the component chemotherapy agents.

6) History of allogeneic bone marrow or organ transplantation

7) Prior Surgery: Major Surgery (including open biopsy) or significant traumatic injury within the last 2 weeks prior to first dose of study treatment or anticipation of the need for major surgery during study treatment. Patients who undergo minor surgical procedures (for example, placement of a central venous access device) must be sufficiently recovered from the procedure to receive chemotherapy but do not require a mandatory 14 day interval between the procedure and initiation of study treatment.

8) Patients who are receiving concurrent antibody or immunotherapy (i.e., interferon-alpha, interferon-beta, interleukin-2, etanercept, infliximab, tacrolimus, cyclosporine, mycophenolic acid, alefacept, or efalizumab) or have received antibody or immunotherapy within 4 weeks prior to receipt of study drug. (For patients entering regimen 5: trastuzumab may have been administered 7 or more days prior to study treatment)

9) Patients who have received investigational agent therapy within 30 days or a period of 5 half-lives of the investigational agent therapy in question (whichever is shorter) prior to the first scheduled day of dosing. (Investigational agent therapy is defined as treatment for which there is currently no regulatory authority approved indication)

10) Administration of high doses of systemic corticosteroids. High dose is considered as > 20 mg of dexamethasone a day (or equivalent) for > 7 consecutive days

11) Any disease (including psychotic/mental disorders, drug abuse, active infection, uncontrolled hypertension, clinically significant cardiovascular disease [for example CVA (</= 6 months before start of treatment), myocardial infarction (</= 6 months beforestart of treatment), unstable angina, NYHA >/= Grade 2 CHF, unstable arrhythmia requiring medication], hepatic, renal or metabolic disease (including uncontrolled diabetes mellitus), metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates

12) (Exclusion #11 continued) the use of an investigational drug or puts the patient at high risk for treatment-related complications

13) Uncontrolled CNS disease (e.g., seizures not controlled with standard medical therapy); patients with brain metastasis who have received radiotherapy and have documented stable disease for > 3 months are eligible for protocol participation. For patients with previous or suspected brain metastasis CT/MRI of the brain is mandatory with 4 weeks prior to start of treatment)

14) Fertile men or women of childbearing potential not using effective methods to prevent pregnancy

15) Lactating women

16) Known HIV or Hepatitis B or C (active, previously treated or both)

17) Administration of any other anti-cancer therapies other than those administered in the individual study regimens

18) EXCLUSION CRITERIA FOR REGIMENS CONTAINING ERLOTINIB: Any known significant ophthalmologic abnormalities of the surface of the eye (the use of contact lenses is not recommended).

19) Patients with current gastrointestinal disease or other condition resulting in an inability to take or absorb oral medications

20) Administration of high doses of systemic corticosteroids. High dose is considered more than 1 mg/kg per day of prednisone (or equivalent) for more than 7 consecutive days. Dexamethasone may induce CYP3A4 activity. CYP3A4 inhibitors and inducers may influence the plasma level of erlotinib.

21) EXCLUSION CRITERIA FOR REGIMENS CONTAINING BEVACIZUMAB: Patients taking an anticoagulant therapy or non-steroidal anti-inflammatory agents (low dose warfarin for venous access devices, and aspirin </= 325 mg/day are permitted).

22) Patients with a baseline proteinuria (as defined by urine protein/creatinine ratio ≥ 1 (spot urine) or 24 hr urine protein of > 1000 mg.

23) Patients with a history or hypertension; blood pressure must be below 140/90 mmHg

24) Patients with a thrombotic or hemorrhagic event within 6 months of study entry

25) Patients with AST or ALT levels >/= 1.5 x ULN concurrent with serum alkaline phosphatase levels of > 2.5 x ULN at baseline

26) Patients with previous major surgery </= 28 days from the start of study treatment, and any surgical incision must be fully healed prior to start of study treatment

27) EXCLUSION CRITERIA FOR REGIMENS CONTAINING DOCETAXEL: Patients with bilirubin > ULN or AST or ALT levels > 1.5 x ULN concurrent with serum alkaline phosphatase levels of > 2.5 x ULN at baseline

28) EXCLUSION CRITERIA FOR REGIMENS CONTAINING 5-FU OR OXALIPLATIN: Patients with severe allergic reactions to fluorouracil, oxaliplatin or other platinum compounds.

29) Patients with pre-existing peripheral neuropathy > CTC grade 2 at start of study

30) EXCLUSION CRITERIA FOR REGIMENS CONTAINING CAPECITABINE: Patients with current gastrointestinal disease or other condition resulting in an inability to take or absorb oral medications.

31) Prior unanticipated severe reaction to fluoropyrimidine therapy (with or without documented DPD deficiency).

32) Requirement for concurrent use of the antiviral agent sorivudine or chemically related analogues, such as brivudine.

33) EXCLUSION CRITERIA FOR REGIMENS CONTAINING TRASTUZUMAB: Patients with cardiac failure manifesting as CHF and decreased LVEF (Patients with an absolute LVEF >/= 10% below the lower limit of normal are ineligible)

34) Cardiac toxicity during prior trastuzumab treatment containing regimens.

35) EXCLUSION CRITERIA FOR REGIMENS CONTAINING TEMOZOLOMIDE: Patients with current gastrointestinal disease or other condition resulting in an inability to take or absorb oral medications.

36) Patients that have had an allergic reaction to hydrazine based drugs (including procarbazine, dacarbazine (DTIC), and temozolomide) or drugs similar to this class of drugs

37) EXCLUSION CRITERIA FOR REGIMENS CONTAINING SORAFENIB: Patients with unstable coronary artery disease or recent myocardial infarction within the past 6 months.

38) Use of CYP3A4 inhibitor or inducers -- (prohibited within 7 days before and during treatment with sorafenib).

39) Patients with sever liver impairment (as defined by Child Pugh Criteria; ie. Child Pugh C patients are excluded)

40) Patients with current gastrointestinal disease or other condition resulting in an inability to take or absorb oral medications.

41) Patients with previous major surgery </= 28 days from the start of study treatment, and any surgical incision must be fully healed prior to start of study treatment.

42) Concomitant use of drugs with the risk of Torsades de Pointes . including but not limited to: Quinidine, procainamide, disopyramide; Amiodarone, sotalol, ibutilide, dofetilide; Erythromycins, clarithromycin; Chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide, ziprasidone; Cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pantamidine, sparfloxacin, lidoflazine;

43) (Exclusion #42 continued) Patients that have discontinued use of these drugs must have at least 5 days or at least 5 half lives of the drug (whichever is greater) prior to the first day of dosing

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Links
Registration Number: NCT00811993
Study Information on Clinical Trials Registry (clinicaltrials.gov)

Other Links:
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Results


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