A Study of R1507 in Combination With Multiple Standard Chemotherapy Treatments in Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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This study will evaluate the safety and tolerability of R1507 in combination with 12 distinct standard chemotherapy drug regimens and an additional R1507 monotherapy arm in patients with advanced malignant neoplasms.The 12 regimens will be tested in parallel. There are 3 subsets of patients who are eligible for the study: untreated, treated and requiring further treatment, or treated and failed and for whom adding R1507 represents a suitable treatment for their disease. All regimens will first test doses of R1507 which are less than the maximally administered dose, and if tolerated, the dose will be escalated in subsequent patients. The anticipated time on study treatment is until disease progression, and the target sample size is 100-500 individuals.

Official Title
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Phase Ib Study To Evaluate The Safety Of Combining IGF-1R Antagonist R1507 With Multiple Standard Chemotherapy Drug Treatments In Patients With Advanced Malignancies

Conditions
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Neoplasms

Intervention / Treatment
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* Drug: RG1507
* Drug: RO1507
* Drug: bevacizumab [Avastin]
* Drug: capecitabine [Xeloda]
* Drug: carboplatin
* Drug: cetuximab
* Drug: docetaxel
* Drug: erlotinib [Tarceva]
* Drug: etoposide
* Drug: gemcitabine
* Drug: irinotecan
* Drug: mFOLFOX6
* Drug: paclitaxel
* Drug: pemetrexel
* Drug: sorafenib
* Drug: temozolomide
* Drug: trastuzumab [Herceptin]


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult patients, >=18 years of age; malignant neoplasms; failed prior standard curative therapy; ECOG performance Status of 0 or 1; adequate bone marrow, hepatic and renal function; life expectancy greater than 8 weeks. Exclusion Criteria: chemotherapy within 2 weeks of start of therapy; prior irradiation within 4 weeks prior to start of therapy; prior treatment with agents targeting IGF-IR inhibition, or other investigational agents; major surgery or significant traumatic injury within 2 weeks prior to study start; patients receiving concurrent antibody or immunotherapy; other exclusion criteria are related to specific treatment regimens.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: RG1507<br>* Starting dose of >=3mg/kg iv escalating to a maximum dose of <=16mg/kg iv, depending on dosing schedule in each combination treatment arm<br>Drug: erlotinib [Tarceva]<br>* as prescribed<br>Drug: gemcitabine<br>* as prescribed<br>|
| Experimental: 10<br> | Drug: RG1507<br>* Starting dose of >=3mg/kg iv escalating to a maximum dose of <=16mg/kg iv, depending on dosing schedule in each combination treatment arm<br>Drug: temozolomide<br>* as prescribed<br>|
| Experimental: 11<br> | Drug: RG1507<br>* Starting dose of >=3mg/kg iv escalating to a maximum dose of <=16mg/kg iv, depending on dosing schedule in each combination treatment arm<br>Drug: bevacizumab [Avastin]<br>* as prescribed<br>Drug: docetaxel<br>* as prescribed<br>|
| Experimental: 12<br> | Drug: RG1507<br>* Starting dose of >=3mg/kg iv escalating to a maximum dose of <=16mg/kg iv, depending on dosing schedule in each combination treatment arm<br>Drug: pemetrexel<br>* as prescribed<br>|
| Experimental: 13<br> | Drug: RO1507<br>* 27mg/kg iv, monotherapy<br>|
| Experimental: 2<br> | Drug: RG1507<br>* Starting dose of >=3mg/kg iv escalating to a maximum dose of <=16mg/kg iv, depending on dosing schedule in each combination treatment arm<br>Drug: bevacizumab [Avastin]<br>* as prescribed<br>Drug: paclitaxel<br>* as prescribed<br>|
| Experimental: 3<br> | Drug: RG1507<br>* Starting dose of >=3mg/kg iv escalating to a maximum dose of <=16mg/kg iv, depending on dosing schedule in each combination treatment arm<br>Drug: carboplatin<br>* as prescribed<br>Drug: etoposide<br>* as prescribed<br>|
| Experimental: 4<br> | Drug: RG1507<br>* Starting dose of >=3mg/kg iv escalating to a maximum dose of <=16mg/kg iv, depending on dosing schedule in each combination treatment arm<br>Drug: bevacizumab [Avastin]<br>* as prescribed<br>Drug: mFOLFOX6<br>* as prescribed<br>|
| Experimental: 5<br> | Drug: RG1507<br>* Starting dose of >=3mg/kg iv escalating to a maximum dose of <=16mg/kg iv, depending on dosing schedule in each combination treatment arm<br>Drug: capecitabine [Xeloda]<br>* as prescribed<br>Drug: trastuzumab [Herceptin]<br>* as prescribed<br>|
| Experimental: 6<br> | Drug: RG1507<br>* Starting dose of >=3mg/kg iv escalating to a maximum dose of <=16mg/kg iv, depending on dosing schedule in each combination treatment arm<br>Drug: sorafenib<br>* as prescribed<br>|
| Experimental: 7<br> | Drug: RG1507<br>* Starting dose of >=3mg/kg iv escalating to a maximum dose of <=16mg/kg iv, depending on dosing schedule in each combination treatment arm<br>Drug: bevacizumab [Avastin]<br>* as prescribed<br>Drug: erlotinib [Tarceva]<br>* as prescribed<br>|
| Experimental: 8<br> | Drug: RG1507<br>* Starting dose of >=3mg/kg iv escalating to a maximum dose of <=16mg/kg iv, depending on dosing schedule in each combination treatment arm<br>Drug: cetuximab<br>* as prescribed<br>Drug: irinotecan<br>* as prescribed<br>|
| Experimental: 9<br> | Drug: RG1507<br>* Starting dose of >=3mg/kg iv escalating to a maximum dose of <=16mg/kg iv, depending on dosing schedule in each combination treatment arm<br>Drug: bevacizumab [Avastin]<br>* as prescribed<br>Drug: carboplatin<br>* as prescribed<br>Drug: paclitaxel<br>* as prescribed<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events, laboratory parameters, vital signs |  | Throughout study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Trough levels of R1507 |  | Throughout study |