BRAF/MEK/EGFR Inhibitor Combination Study in Colorectal Cancer (CRC)

NCT ID: NCT01750918

Last Updated: 2021-10-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 166 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-12-19
• Study Completion Date: 2020-06-18

Brief Summary

This was a four part, phase I/II study aimed to evaluate the safety, tolerability and efficacy of combination of an anti-EGFR antibody panitumumab (P) either with a BRAF inhibitor (dabrafenib (D); GSK2118436) alone or with the combination of a BRAF inhibitor and a MEK inhibitor (trametinib (T); GSK1120212) in patients with BRAF-mutant V600E advanced or mCRC. The goal was to: 1) Determine RP2R/MTD for doublet (D+P) and triplet (D+T+P) combinations in Part 1; 2) Assess clinical activity for these combinations in Part 2; 3) Determine RP2R/MTD for double (T+P) combination in Part 4A, and assess clinical activity of this combination in two patient populations in Part 4B (patients with BRAF-V600E mutation-positive advanced or metastatic CRC and patients with advanced or metastatic CRC with secondary resistance to anti-EGFR therapy).

Detailed Description

Part 1: Dose escalation This was a dose escalation part intended to evaluate safety, tolerability, PK, PD, clinical activity and determine RP2R/MTD for the doublet (D+P) and the triplet (D+T+P) combinations in patients with BRAF-mutation V600E positive advanced or metastatic CRC. A 3+3 dose escalation procedure was followed. Dosing for dabrafenib and trametinib was continuous daily dosing while panitumumab was dosed once every two weeks (Q2W). Patients were evaluated for dose-limiting toxicities (DLTs) during the first 28 days of treatment.

Part 2A:

This was a cohort expansion part to assess the safety and preliminary clinical activity of the optimal safe and tolerable dose combinations (D+P)/(D+T+P) defined in Part 1.

Part 2B:

In this part, additional patients were enrolled into the triplet (D+T+P) combination at two dose levels in to further explore safety, tolerability and clinical activity. Up to 10 patients each with no prior treatment (First Line Population), and up to 20 patients each with at least one prior treatment (Second to Fourth Line Population) were planned to be enrolled in dose Cohorts 3A and 4.

Part 3: Randomized Phase 2 Study The randomized phase 2 portion (Phase 3) of the study was not pursued as the observed responses in any of the cohorts did not meet the predefined criteria at the time of the preliminary analysis (data cut-off date: 06-May-2016).

Part 4 This part was designed to identify the RP2R/MTD and initial clinical activity for the doublet (T+P) combination in patients BRAF-mutation V600E positive advanced or metastatic CRC, and advanced or metastatic CRC with secondary resistance to prior anti-EGFR therapy.

Part 4A: Dose Escalation This was a dose escalation part intended to determine RP2R/MTD for the doublet (T+P) combination in patients with BRAF-mutation V600E positive advanced or metastatic CRC. Approximately 18 patients (~6 each cohort) were planned to be enrolled in Part 4A. A 3+3 dose escalation procedure was followed. Dosing for trametinib was continuous daily dosing while panitumumab was dosed once every two weeks (Q2W). Patients were evaluated for DLTs during the first 28 days of treatment.

Part 4B: Cohort Expansion This was a cohort expansion part intended to evaluate safety and efficacy of the doublet (T+P) combination. Up to 20 patients in each of two expansion cohorts were planned to be enrolled at the starting dose cohort or MTD from Part 4A.

Conditions

Cancer

Keywords

MEK inhibitor; anti-EGFR antibody; colorectal cancer; BRAF inhibitor

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part 1: Dabrafenib and Panitumumab

In Part 1 subjects will be assigned to escalation cohort of the doublet of dabrafenib and panitumumab based on the monotherapy doses of dabrafenib (150 milligrams \[mg\] twice daily) and panitumumab (6 milligrams per kilogram \[mg/kg\] every-2-week \[Q2W\]). Dose escalation will follow a 3+3 dose escalation procedure. If the initial combination dose of dabrafenib and panitumumab in Cohort 1 (starting dose) is not tolerable, lower dose combination(s) may be evaluated.

Group Type: EXPERIMENTAL

Dabrafenib

Intervention Type: DRUG

Each capsule contains 50 mg or 75 mg of GSK2118436; 50 mg strength capsules are Swedish orange (dark red) opaque hypromellose size 2 capsules and 75 mg strength capsules are pink opaque hypromellose size 1 capsules. The initial dosing regimen will be twice daily (BID) continuous oral daily dosing.

Panitumumab

Intervention Type: DRUG

Panitumumab is a sterile, colorless, translucent-to-white amorphous, proteinaceous powder available as 100 mg panitumumab in 5 mL (20 mg/mL) single-use vial; 200 mg panitumumab in 10 mL (20 mg/mL) single-use vial; 400 mg panitumumab in 20 mL (20 mg/mL) single-use vial; to be administered as an intravenous infusion over 60 minutes, every 14 days. Doses higher than 1000 mg should be administered over 90 minutes.

Part 1: Dabrafenib, Trametinib and Panitumumab

In Part 1 after the dabrafenib/panitumumab combination dose is defined, subsequent cohorts will evaluate the addition of trametinib based on a panitumumab dose that is one dose level lower than the dabrafenib/panitumumab dose defined in Cohort 1. Trametinib starting at 1.5 mg once daily will be added to the combination of dabrafenib and panitumumab. Dose escalation will follow a 3+3 dose escalation procedure until the full monotherapy doses of all agents are evaluated or the maximum tolerated dose is determined.

Group Type: EXPERIMENTAL

Dabrafenib

Intervention Type: DRUG

Each capsule contains 50 mg or 75 mg of GSK2118436; 50 mg strength capsules are Swedish orange (dark red) opaque hypromellose size 2 capsules and 75 mg strength capsules are pink opaque hypromellose size 1 capsules. The initial dosing regimen will be twice daily (BID) continuous oral daily dosing.

Trametinib

Intervention Type: DRUG

Each tablet contains 0.5mg or 2.0 mg GSK1120212; 0.5 mg is yellow modified oval biconvex film-coated tablets of size 4.8 mm X 8.9 mm and 2 mg as pink round biconvex film coated tablets;7.5 mm in diameter. The initial dosing regimen will be once daily continuous oral daily dosing.

Panitumumab

Intervention Type: DRUG

Panitumumab is a sterile, colorless, translucent-to-white amorphous, proteinaceous powder available as 100 mg panitumumab in 5 mL (20 mg/mL) single-use vial; 200 mg panitumumab in 10 mL (20 mg/mL) single-use vial; 400 mg panitumumab in 20 mL (20 mg/mL) single-use vial; to be administered as an intravenous infusion over 60 minutes, every 14 days. Doses higher than 1000 mg should be administered over 90 minutes.

Part 2: Dabrafenib and panitumumab

In Part 2, subjects will be assigned to expansion cohorts at a selected dose of dabrafenib in combination with panitumumab

Group Type: EXPERIMENTAL

Dabrafenib

Intervention Type: DRUG

Each capsule contains 50 mg or 75 mg of GSK2118436; 50 mg strength capsules are Swedish orange (dark red) opaque hypromellose size 2 capsules and 75 mg strength capsules are pink opaque hypromellose size 1 capsules. The initial dosing regimen will be twice daily (BID) continuous oral daily dosing.

Panitumumab

Intervention Type: DRUG

Panitumumab is a sterile, colorless, translucent-to-white amorphous, proteinaceous powder available as 100 mg panitumumab in 5 mL (20 mg/mL) single-use vial; 200 mg panitumumab in 10 mL (20 mg/mL) single-use vial; 400 mg panitumumab in 20 mL (20 mg/mL) single-use vial; to be administered as an intravenous infusion over 60 minutes, every 14 days. Doses higher than 1000 mg should be administered over 90 minutes.

Part 2: Dabrafenib, Trametinib and Panitumumab

In Part 2, subjects will be assigned to expansion cohorts at selected dose of trametinib plus dabrafenib in combination with panitumumab.

Group Type: EXPERIMENTAL

Dabrafenib

Intervention Type: DRUG

Each capsule contains 50 mg or 75 mg of GSK2118436; 50 mg strength capsules are Swedish orange (dark red) opaque hypromellose size 2 capsules and 75 mg strength capsules are pink opaque hypromellose size 1 capsules. The initial dosing regimen will be twice daily (BID) continuous oral daily dosing.

Trametinib

Intervention Type: DRUG

Each tablet contains 0.5mg or 2.0 mg GSK1120212; 0.5 mg is yellow modified oval biconvex film-coated tablets of size 4.8 mm X 8.9 mm and 2 mg as pink round biconvex film coated tablets;7.5 mm in diameter. The initial dosing regimen will be once daily continuous oral daily dosing.

Panitumumab

Intervention Type: DRUG

Panitumumab is a sterile, colorless, translucent-to-white amorphous, proteinaceous powder available as 100 mg panitumumab in 5 mL (20 mg/mL) single-use vial; 200 mg panitumumab in 10 mL (20 mg/mL) single-use vial; 400 mg panitumumab in 20 mL (20 mg/mL) single-use vial; to be administered as an intravenous infusion over 60 minutes, every 14 days. Doses higher than 1000 mg should be administered over 90 minutes.

Part 4a: Trametinib and Panitumumab

Subject will be administered starting dose of Trametinib 2 mg once daily and Panitumumab 6mg/kg Q2W. If the initial combination dose of trametinib and panitumumab in Cohort 1 (starting dose) is not tolerable, the lower dose combination defined in de-escalation cohorts (Cohort -1A, -1B and/or -1C) may be evaluated. Cohort -1A: Trametinib 1.5 mg once daily and Panitumumab 6 mg/kg Q2W; Cohort -1B: Trametinib 2 mg once daily and Panitumumab 4.8 mg/kg Q2W; Cohort-1C: Trametinib 1.5 mg once daily and Panitumumab 4.8 mg/kg Q2W

Group Type: EXPERIMENTAL

Trametinib

Intervention Type: DRUG

Each tablet contains 0.5mg or 2.0 mg GSK1120212; 0.5 mg is yellow modified oval biconvex film-coated tablets of size 4.8 mm X 8.9 mm and 2 mg as pink round biconvex film coated tablets;7.5 mm in diameter. The initial dosing regimen will be once daily continuous oral daily dosing.

Panitumumab

Intervention Type: DRUG

Panitumumab is a sterile, colorless, translucent-to-white amorphous, proteinaceous powder available as 100 mg panitumumab in 5 mL (20 mg/mL) single-use vial; 200 mg panitumumab in 10 mL (20 mg/mL) single-use vial; 400 mg panitumumab in 20 mL (20 mg/mL) single-use vial; to be administered as an intravenous infusion over 60 minutes, every 14 days. Doses higher than 1000 mg should be administered over 90 minutes.

Part 4b: Trametinib and Panitumumab

In Part 4B cohort expansion, subjects will be assigned to expansion cohorts at a selected dose of trametinib in combination with panitumumab. Enrollment in expansion cohorts will be initiated once dose escalation for the trametinib /panitumumab combination has been completed. Subjects with advanced/metastatic CRC with either a BRAF-mutation (Cohort 1E) or who developed secondary resistance to prior anti-EGFR therapy (Cohort 2E).

Group Type: EXPERIMENTAL

Trametinib

Intervention Type: DRUG

Each tablet contains 0.5mg or 2.0 mg GSK1120212; 0.5 mg is yellow modified oval biconvex film-coated tablets of size 4.8 mm X 8.9 mm and 2 mg as pink round biconvex film coated tablets;7.5 mm in diameter. The initial dosing regimen will be once daily continuous oral daily dosing.

Panitumumab

Intervention Type: DRUG

Panitumumab is a sterile, colorless, translucent-to-white amorphous, proteinaceous powder available as 100 mg panitumumab in 5 mL (20 mg/mL) single-use vial; 200 mg panitumumab in 10 mL (20 mg/mL) single-use vial; 400 mg panitumumab in 20 mL (20 mg/mL) single-use vial; to be administered as an intravenous infusion over 60 minutes, every 14 days. Doses higher than 1000 mg should be administered over 90 minutes.

Part 3a: Dabrafenib and Panitumumab

Subjects will be randomized to receive dabrafenib plus panitumumab. Dose levels for dabrafenib, and panitumumab in Part 3 will be chosen based on emerging PK, PD, and tolerability data from Part 1 and Part 2.

Group Type: EXPERIMENTAL

Dabrafenib

Intervention Type: DRUG

Each capsule contains 50 mg or 75 mg of GSK2118436; 50 mg strength capsules are Swedish orange (dark red) opaque hypromellose size 2 capsules and 75 mg strength capsules are pink opaque hypromellose size 1 capsules. The initial dosing regimen will be twice daily (BID) continuous oral daily dosing.

Panitumumab

Intervention Type: DRUG

Panitumumab is a sterile, colorless, translucent-to-white amorphous, proteinaceous powder available as 100 mg panitumumab in 5 mL (20 mg/mL) single-use vial; 200 mg panitumumab in 10 mL (20 mg/mL) single-use vial; 400 mg panitumumab in 20 mL (20 mg/mL) single-use vial; to be administered as an intravenous infusion over 60 minutes, every 14 days. Doses higher than 1000 mg should be administered over 90 minutes.

Part 3b: Dabrafenib, Trametinib and Panitumumab

Subjects will be randomized to receive study treatment as dabrafenib plus trametinib plus panitumumab. Dose levels for dabrafenib, trametinib and panitumumab in Part 3 will be chosen based on emerging PK, PD, and tolerability data from Part 1 and Part 2.

Group Type: EXPERIMENTAL

Dabrafenib

Intervention Type: DRUG

Each capsule contains 50 mg or 75 mg of GSK2118436; 50 mg strength capsules are Swedish orange (dark red) opaque hypromellose size 2 capsules and 75 mg strength capsules are pink opaque hypromellose size 1 capsules. The initial dosing regimen will be twice daily (BID) continuous oral daily dosing.

Trametinib

Intervention Type: DRUG

Each tablet contains 0.5mg or 2.0 mg GSK1120212; 0.5 mg is yellow modified oval biconvex film-coated tablets of size 4.8 mm X 8.9 mm and 2 mg as pink round biconvex film coated tablets;7.5 mm in diameter. The initial dosing regimen will be once daily continuous oral daily dosing.

Part 3c: Chemotherapy comparator

Subjects will be randomized to receive chemotherapy comparator. The chemotherapy comparator will consist of a standard chemotherapy regimen with or without the addition of a biological agent, based on local practice preferences. The available chemotherapy regimens includes 5-fluorouracil-based chemotherapy

Group Type: EXPERIMENTAL

5-fluorouracil

Intervention Type: DEVICE

5-fluorouracil-based chemotherapy

Interventions

Dabrafenib

Each capsule contains 50 mg or 75 mg of GSK2118436; 50 mg strength capsules are Swedish orange (dark red) opaque hypromellose size 2 capsules and 75 mg strength capsules are pink opaque hypromellose size 1 capsules. The initial dosing regimen will be twice daily (BID) continuous oral daily dosing.

Intervention Type: DRUG

Trametinib

Each tablet contains 0.5mg or 2.0 mg GSK1120212; 0.5 mg is yellow modified oval biconvex film-coated tablets of size 4.8 mm X 8.9 mm and 2 mg as pink round biconvex film coated tablets;7.5 mm in diameter. The initial dosing regimen will be once daily continuous oral daily dosing.

Intervention Type: DRUG

Panitumumab

Panitumumab is a sterile, colorless, translucent-to-white amorphous, proteinaceous powder available as 100 mg panitumumab in 5 mL (20 mg/mL) single-use vial; 200 mg panitumumab in 10 mL (20 mg/mL) single-use vial; 400 mg panitumumab in 20 mL (20 mg/mL) single-use vial; to be administered as an intravenous infusion over 60 minutes, every 14 days. Doses higher than 1000 mg should be administered over 90 minutes.

Intervention Type: DRUG

5-fluorouracil

5-fluorouracil-based chemotherapy

Intervention Type: DEVICE

Other Intervention Names

GSK2118436, DRB436; GSK1120212, TMT212

Eligibility Criteria

Inclusion Criteria

• Provided written informed consent,
• Male or female >=18 years of age and able to swallow and retain orally administered study treatment and does not have any clinically significant gastrointestinal (GI) abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach and/or bowels.
• Part 1 and Part 2: Histologically- or cytologically-confirmed diagnosis of advanced or metastatic BRAF V600E mutation positive CRC
• Part 4A and 4B ONLY: Histologically- or cytologically-confirmed diagnosis of advanced or metastatic CRC that either harbours the BRAF V600E -mutation, as determined by relevant genetic testing OR has developed secondary resistance to anti-EGFR therapy, defined as patients that derived benefit (disease control based on investigator assessment for >6 months OR partial response [confirmed or unconfirmed] based on RECIST 1.1) from prior anti-EGFR-containing therapy (as defined below) and then subsequently progressed on therapy. The anti-EGFR therapy must have been the most recent therapy and the patient must have progressed based on investigator assessment within 3 months of screening. Acceptable prior anti-EGFR-containing therapies include: a. Monotherapy anti-EGFR, including cetuximab or panitumumab OR b. irinotecan/anti-EGFR combo after previously having disease progression (based on investigator assessment) on an irinotecan-containing regimen
• Part 3: Histologically- or cytologically-confirmed diagnosis of BRAFV600E mutation positive advanced or metastatic colorectal cancer (CRC who are eligible to receive fluoropyrimidine-containing chemotherapy regimen that have experienced documented radiographic progression on one prior line of fluoropyrimidine-containing chemotherapy (previous anti-EGFR therapy is excluded), Second-line for advanced/metastatic disease, having failed or been intolerant to at least one regimen of fluoropyrimidine-containing chemotherapy including irinotecan or oxaliplatin in the advanced/metastatic setting. Enrollment in Part 3 may only occur following confirmation of KRAS wild-type cancer.
• Archival tissue is required; if archival tissue is not available or found to not contain tumor tissue, a fresh biopsy is required.
• Measurable disease per RECIST version 1.1.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
• Men with a female partner of childbearing potential must have either had a prior vasectomy or agree to use one of the contraception methods listed in protocol.
• Female subjects are eligible if: Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or post-menopausal female defined as 12 months of spontaneous amenorrhea to be verified with a follicle-stimulating hormone (FSH) level >40 Milli-international units per milliliter (MIU/mL) and estradiol level <40 picogram per milliliter (pg/mL). Child-bearing potential and agrees to use one of the contraceptive methods listed in protocol.
• Female subjects must agree to use contraception from 7 days prior to the first dose of study drug(s) until 6 months after the last dose of panitumumab, until 4 months after the last dose of trametinib, or 4 weeks after the last dose of dabrafenib, whichever is longer. Additionally, women of childbearing potential must have had a negative serum pregnancy test within 7 days prior to the first dose of study drug(s).
• Adequate organ system function as defined in absolute neutrophil count greater than or equal to 1.2X10^9/Liter (L), hemoglobin greater than or equal to 9 grams per deciliter (g/dL) or 5.6 millimoles per litre (mmol/L), platelets greater than or equal to 75 × 10^9/L, Prothrombin Time / International Normalized Ratio (PT/INR) and Partial Thromboplastin Time (PTT) less than or equal to 1.5X upper limit of normal (ULN); serum magnesium greater than or equal to the lower limit of normal (LLN); albumin greater than or equal to 2.5 g/dL or 25 grams per liter (g/L), total bilirubin less than or equal to 1.5XULN, and Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) less than or equal to 2.5X ULN; creatinine less than or equal to 1.5XULN or calculated creatinine clearance greater than or equal to 50mL/min; left ventricular ejection fraction (LVEF) greater than or equal to the LLN by echocardiography (ECHO) or multigated acquisition scan (MUGA).
• Subjects enrolled in France or Italy: In France or Italy, a subject will be eligible for inclusion in this study only if either affiliated to, or a beneficiary of, a social security category.

• History of retinal vein occlusion (RVO).
• Presence of active gastrointestinal disease or other condition that will interfere significantly with the absorption, distribution, metabolism or excretion of drugs. Previous colectomy is acceptable.
• Subjects with brain metastases are excluded, unless: All known lesions must be previously treated with surgery or stereotactic radio-surgery, and Brain lesion(s), if present, must be confirmed stable (i.e., no increase in lesion size) for >=90 days prior to first dose of study drug(s). This must be documented with two consecutive MRI or CT scans using contrast, and Asymptomatic with no corticosteroids requirement for >=30 days prior to first dose of study drug(s), and No enzyme-inducing anticonvulsants for >=14 days prior to first dose of study drug(s). In addition, for subjects that had brain metastases but currently have no evidence of disease (NED), NED for >=12 weeks is required and must be confirmed by two consecutive MRI or CT scans (using contrast) separated by >=6 weeks, prior to randomization. Enrollment of a subject with brain metastases who meet the above criteria requires approval of a GlaxoSmithKline (GSK) Medical Monitor.
• Psychological, familial, sociological or geographical conditions that do not permit compliance with the protocol.
• History or evidence of cardiovascular risk including any of the following: LVEF<LLN; A QT interval corrected for heart rate using the Bazett's formula (QTcB;) ≥ 480 milliseconds (msec);.History or evidence of current clinically significant uncontrolled arrhythmias. Exception: Subjects with controlled atrial fibrillation for >30 days prior to randomization are eligible. History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to randomization. History or evidence of current >= Class II congestive heart failure as defined by New York Heart Association (NYHA). Treatment refractory hypertension defined as a blood pressure of systolic> 140 millimeter of mercury (mm Hg) and/or diastolic > 90 mm Hg which cannot be controlled by anti-hypertensive therapy; Subjects with intra-cardiac defibrillators or permanent pacemakers; Known cardiac metastases
• Unstable pulmonary embolism, deep vein thrombosis, or other significant arterial/venous thromboembolic event <=30 days before randomization. If on anticoagulation, subject must be on stable therapeutic dose prior to randomization.
• Subjects with a history of pneumonitis or interstitial lung disease (ILD).
• Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study drug(s) or their excipients.
• Pregnant or lactating female.
• Unwillingness or inability to follow the procedures outlined in the protocol.
• Uncontrolled diabetes or other medical condition that may interfere with assessment of toxicity.

Exclusion Criteria

• History of prior malignancy, other than colorectal cancer.
• Any serious and/or unstable pre-existing medical, psychiatric disorder or other conditions that could interfere with subject's safety, obtaining informed consent or compliance to the study procedures.
• Current active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones, liver metastases or otherwise stable chronic liver disease per investigator's assessment).
• History of sensitivity to heparin or heparin-induced thrombocytopenia.
• Currently receiving cancer therapy (chemotherapy, radiation therapy, immunotherapy or biologic therapy).
• Prior exposure to a MEK inhibitor.
• Part 1, Part 2 and BRAF-mutant patients in Part 4 ONLY: Prior exposure to a BRAF inhibitor.
• Part 1, Part 2 and BRAF-mutant patients in Part 4 ONLY: Known presence of KRAS-mutation based on previous KRAS-testing. Note: Prospective KRAS testing is not required. However, if the results of previous KRAS testing are known, they must be used in assessing eligibility. KRAS testing will be performed retrospectively for all patients.
• Part 3: Prior exposure to EGFR inhibitors or an anti-EGFR antibody
• Received an investigational or approved anti-cancer drug within 4 weeks, or within 5 half-lives (whichever is shorter) of the first dose of study drug(s). At least 14 days must have passed between the last dose of prior investigational agent and the first dose of study drug(s).
• Part 3: Received more than one prior anti-cancer therapy in the metastatic setting, exclusive of previous adjuvant regimens. Previous investigational anti-cancer therapy in the metastatic setting is prohibited.
• Current use of a prohibited medication or requirement to dose with any of these medications during treatment with study drug(s).
• Known Hepatitis B, or Hepatitis C infection.
• Any major surgery, radiotherapy or immunotherapy within the 4 weeks prior to first dose of study drug(s). Limited radiotherapy with in the 2 weeks prior to first dose of study drug(s).
• Chemotherapy regimens with delayed toxicity within the 3 weeks prior to first dose of study drug(s). Chemotherapy regimens given continuously or on a weekly basis with limited potential for delayed toxicity within 2 weeks prior to first dose of study drug(s).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Novartis Investigative Site

Scottsdale, Arizona, United States

Novartis Investigative Site

San Francisco, California, United States

Novartis Investigative Site

Boston, Massachusetts, United States

Novartis Investigative Site

Boston, Massachusetts, United States

Novartis Investigative Site

New York, New York, United States

Novartis Investigative Site

Chapel Hill, North Carolina, United States

Novartis Investigative Site

Philadelphia, Pennsylvania, United States

Novartis Investigative Site

Nashville, Tennessee, United States

Novartis Investigative Site

Brussels, , Belgium

Novartis Investigative Site

Leuven, , Belgium

Novartis Investigative Site

Paris, , France

Novartis Investigative Site

Villejuif, , France

Novartis Investigative Site

Candiolo, , Italy

Novartis Investigative Site

Milan, , Italy

Novartis Investigative Site

Aichi, , Japan

Novartis Investigative Site

Chiba, , Japan

Novartis Investigative Site

Amsterdam, , Netherlands

Novartis Investigative Site

Utrecht, , Netherlands

Novartis Investigative Site

Barcelona, , Spain

Novartis Investigative Site

Birmingham, , United Kingdom

Countries

United States; Belgium; France; Italy; Japan; Netherlands; Spain; United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

CDRB436C2201

Identifier Type: OTHER

Identifier Source: secondary_id

2012-004802-81

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

116833

Identifier Type: -

Identifier Source: org_study_id