Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Melanoma

Sarcoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Soft Tissue Sarcoma

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Ipilimumab

Carbamide Peroxide

Vemurafenib

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Injection, intravenous (i.v.), cohort 1: 3 mg/kg, Escalate to cohort 2: 10 mg/kg, Escalate to cohort 3: at Recommended Phase 2 Dose (RP2D), De-escalate cohort 1A: 3 mg/kg, De-escalate cohort -1B: 10 mg/kg, (every three week) Q3wk, upto 2 yrs

Ipilimumab (BMS-734016)

tablets, oral, cohort 1: 960 mg Twice daily (BID) x 28 days after date, cohort 2: 960 mg BID x 28 days after date, cohort 3: at Recommended Phase 2 Dose (RP2D) x 14 days after date, De-escalate cohort 1A: 720 mg BID x 28 days after date, De-escalate cohort -1B: 720 mg BID x 28 days after date , Up to 2 yrs

Bristol-Myers Squibb

Treatment of subjects who have metastatic melanoma that expresses an activated mutant form of the BRAF oncogene (V600E) with a combination of the specific BRAF inhibitor, Vemurafenib, and the Cytotoxic T Lymphocyte Antigen 4 (CTLA-4) inhibitor mAb Ipilimumab will be safe and feasible and will show preliminary evidence of anti-tumor efficacy and survival in comparison to historical results following treatment with either agent alone.

Ph I Ipilimumab Vemurafenib Combo in Patients With v-Raf Murine Sarcoma Viral Oncogene Homolog B1 (BRAF)

A Phase I Trial of Vemurafenib and Ipilimumab in Subjects With V600 BRAF Mutation-positive Metastatic Melanoma

AEs graded using National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0. AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4= Potentially Life-threatening or disabling, Gr 5=Death. Related=relationship to study drug reported as certain, probable, possible, or missing. Immune-related AEs (irAEs) characterized by potential association with inflammation and considered by investigator as drug related. Lead In Period: between the first vemurafenib dose and the day prior to the first ipilimumab dose.

AEs graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0. AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4= Potentially Life-threatening or disabling, Gr 5=Death. Related=relationship to study drug reported as certain, probable, possible, or missing. AEs: onset on or after ipilimumab start and within 90 days of last dose. Immune-related AEs (irAEs) characterized by potential association with inflammation and considered by investigator as drug related. Day 1=first dose of ipilimumab.

DLT defined as a \>= Grade 3 drug-related AE during induction with ipilimumab in combination with vemurafenib excluding: Grade 3 AE of tumor flare (defined as local pain, irritation, or rash localized at sites of known or suspected tumor); Grade 3 cutaneous squamous cell carcinoma; Grade 3 photosensitivity that resolved to a Grade 1 or baseline within 15 days; Grade 3 immune-mediated events of the skin (rash, pruritis) or endocrine systems (hypothyroidism, hyperthyroidism, hypopituitarism, adrenal insufficiency, hypogonadism and cushingoid) that resolved to a Grade 1 or baseline within 28 days; a transient (resolving within 6 hours of onset) Grade 3 infusion-related AE. Hepatic=elevated aspartate aminotransferase and alanine aminotransferase. Maximum tolerable dose (MTD) was defined as the maximum dose of combination treatment that could be given to 6 subjects such that no more than 2 subjects experience DLT. Day 1=first day of concurrent therapy with ipilimumab and vemurafenib.

Roche-Genentech

Final safety follow-up was 23 December 2013.

Lead In Period: 28 Days of 960 mg vemurafenib orally twice daily (starting Day -27 or -13).

Events between the first vemurafenib dose and the day prior to the first ipilimumab dose.

Lead-In Period 960 mg Vemurafenib

Lead In Period: 28 Days of 720 mg vemurafenib orally twice daily (starting Day -27 or -13).

Events between the first vemurafenib dose and the day prior to the first ipilimumab dose.

Lead-In Period 720 mg Vemurafenib

These participants were receiving 720 mg vemurafenib in the Lead in Period prior to starting ipilimumab but after the DLTs were identified, ipilimumab was not started. Due to disease stabilization, they continued on 720 mg vemurafenib alone orally twice daily.

Lead- In Period 720 mg Vemurafenib Alone

3 mg/kg ipilimumab intravenously once every 3 weeks for 4 weeks (Week 1, Week 4, Week 7, Week 10) starting on Day 1 plus 960 mg vemurafenib orally twice daily and continuing during combination treatment.

3 mg/kg Ipilimumab + 960 mg Vemurafenib

3 mg/kg ipilimumab intravenously once every 3 weeks for 4 weeks (Week 1, Week 4, Week 7, Week 10) starting on Day 1 plus 720 mg vemurafenib orally twice daily continuing during combination treatment.

3 mg/kg Ipilimumab + 720 mg Vemurafenib

Lead In Period: 28 Days of 960 mg vemurafenib orally twice daily (starting Day -27 or -13).

Combination Treatment (Induction of ipilimumab) Period: 3 milligrams per kilogram body weight (mg/kg) ipilimumab intravenously once every 3 weeks for 4 weeks (Week 1, Week 4, Week 7, Week 10) starting on Day 1, plus 960 mg vemurafenib orally twice daily throughout combination treatment.

Lead In Period: 28 Days of 720 mg vemurafenib orally twice daily (starting Day -27 or -13).

Combination Treatment (Induction of ipilimumab) Period: 3 milligrams per kilogram body weight (mg/kg) ipilimumab intravenously once every 3 weeks for 4 weeks (Week 1, Week 4, Week 7, Week 10) starting on Day 1 plus 720 mg vemurafenib orally twice daily throughout combination treatment.

These participants were receiving 720 mg vemurafenib in the Lead in Period prior to starting ipilimumab but after the dose limiting toxicities (DLTs) were identified, ipilimumab was not started. Due to disease stabilization, they continued on 720 mg vemurafenib alone orally twice daily.

720 mg Vemurafenib

Total

Age, Categorical

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

All participants who received at least one dose of study drug.

In Phase 1 of the study, MTD was not reached because more than 2 of 6 treated participants experienced DLTs with the combination therapy. Enrollments in Phase 1 were terminated and Phase 2 was not started so only overall safety was summarized.

Bristol-Myers Squibb Study Director

Deaths

Deaths due to disease progression

Grade 3 SAEs

Grade 4 SAEs

Grade 5 SAEs

Drug Related Grade 3 SAEs

Drug Related Grade 4 SAEs

AEs Leading to Study Drug Discontinuation

Grade 1 irAEs

Grade 2 irAEs

Grade 3 irAEs

Grade 4 irAEs

Grade 1 AEs

Grade 2 AEs

Grade 3 AEs

Grade 4 AEs

Grade 5 AEs

Drug Related Grade 1 AEs

Drug Related Grade 2 AEs

Drug Related Grade 3 AEs

Drug Related Grade 4 AEs

960 mg Vemurafenib Lead in Period

720 mg Vemurafenib Lead in Period

These participants were receiving 720 mg vemurafenib in the Lead in Period prior to starting ipilimumab but after the DLTs were identified, ipilimumab was not started. Due to disease stabilization, they continued on 720 mg vemurafenib alone orally twice daily.

Events from first day of vemurafenib to last day of treatment + 90 days, up to date of data cut off for Primary Endpoint.

720 mg Vemurafenib Alone

During the Lead In Period: Number of Participants With Adverse Events (AEs), AEs Leading to Drug Discontinuation, Serious Adverse Events (SAEs), and Deaths in Participants Treated With Vemurafenib Alone

During the Combination Treatment Period: Number of Participants With Adverse Events (AEs), AEs Leading to Drug Discontinuation, Serious Adverse Events (SAEs), and Deaths in Participants Treated With Concurrent Ipilimumab and Vemurafenib

3 mg/kg ipilimumab intravenously once every 3 weeks for 4 weeks (Week 1, Week 4, Week 7, Week 10) starting on Day 1 plus 960 mg vemurafenib orally twice daily continuing during combination treatment.

All participants who received at least one dose of concurrent study drugs.

Number of Participants With Hepatic Dose Limiting Toxicities (DLT) in Participants Treated With Concurrent Ipilimumab and Vemurafenib

Lead In Period: 28 Days of 960 mg vemurafenib orally twice daily (starting Day -27 or -13).

Combination Treatment (Induction of ipilimumab) Period: 3 milligrams per kilogram body weight (mg/kg) ipilimumab intravenously once every 3 weeks for 4 weeks (Week 1, Week 4, Week 7, Week 10) starting on Day 1 plus 960 mg vemurafenib orally twice daily throughout combination treatment.

These participants were receiving 720 mg vemurafenib in the Lead in Period prior to starting ipilimumab but after the dose limiting toxicities (DLTs) were identified ipilimumab was not started. Due to disease stabilization, they continued on 720 mg vemurafenib alone orally twice daily. Note: the dose of vemurafenib could be escalated from 720 mg to 960 mg, at the investigator's discretion.

Spots Global Cancer Trial Database for Ph I Ipilimumab Vemurafenib Combo in Patients With v-Raf Murine Sarcoma Viral Oncogene Homolog B1 (BRAF)

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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