Pilot Ipilimumab in Stage IV Melanoma Receiving Palliative Radiation Therapy

NCT01449279 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: IRB-21970SU-08242011-8306MEL0005
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

To determine the safety of local palliative radiation therapy used in combination with anti-CTLA-4 immunotherapy.

Conditions

Melanoma

Outcome Measures

Primary Outcomes (1)

• Safety Measurement - Percentage of Patients Experiencing Serious Adverse Events (SAEs) in the First 4 Months of Treatment.

  Serious adverse events (SAEs) defined as untoward medical occurrence that at any dose: results in death, is life-threatening (defined as an event in which the subject was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe), requires in subject hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event (defined as a medical event(s) that may not be immediately life-threatening or result in death or hospitalization but, may jeopardize the subject or may require intervention to prevent one of the other serious outcomes listed in the definition above.)

  4 months

Secondary Outcomes (7)

• Response Rate

  2 to 4 weeks after last ipilimumab dose then every 3 months +/- 2 weeks until progression of disease

• Overall Survival

  2 to 4 weeks after last ipilimumab dose then every 3 months +/- 2 weeks until progression of disease

• Duration of Complete Response

  2 to 4 weeks after last ipilimumab dose then every 3 months +/- 2 weeks until progression of disease

• Duration of Partial Response.

  2 to 4 weeks after last ipilimumab and then every 3 months until disease progression.

• Stable Disease

  2 to 4 weeks after last ipilimumab and then every 3 months until disease progression.

Study Arms (1)

Ipilimumab Treatment + Radiation Therapy

EXPERIMENTAL

Ipilimumab (BMS-734016, MDX010, MDX-CTLA4, Yervoy) will be administered as standard of care with base dose of 3 mg/kg iv over approximately 90 minutes every 3 weeks for a total of 4 treatments. Palliative radiation therapy to 1 to 2 sites of disease will start within 5 days of the first ipilimumab dose. Subjects will have follow up visits 2 to 4 weeks after the last ipilimumab dose and then every 3 months (±2 weeks) thereafter until progression of disease.

Drug: Ipilimumab; Radiation: Radiation Therapy

Interventions

Ipilimumab DRUG

Ipilimumab will be administered as a single agent standard of care with base dose of 3 mg/kg iv over approximately 90 minutes every 3 weeks for a total of 4 treatments.

Also known as: MDX-101, Yervoy

Ipilimumab Treatment + Radiation Therapy

Radiation Therapy RADIATION

Standard of care palliative radiation therapy will start within 5 days of the first ipilimumab dose. Dose is dependent upon lesion size and is determined by the radiation oncologist.

Also known as: radiotherapy, radiation oncology

Ipilimumab Treatment + Radiation Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed Written Informed Consent
• Before any study procedures are performed, subjects (or their legally acceptable representatives) will have the details of the study described to them, and they will be given a written informed consent document to read. Then, if subjects consent to participate in the study, they will indicate that consent by signing and dating the informed consent document in the presence of study personnel.
• Target Population
• Histologically confirmed Stage IV melanoma.
• Must have failed at least one systemic therapy for malignant melanoma or be intolerant to at least one prior systemic treatment.
• Subjects with asymptomatic brain metastases are eligible. (Systemic steroids should be avoided if possible, or the subject should be stable on the lowest clinically effective dose, as steroids as they may interfere with the activity of ipilimumab if administered at the time of the first ipilimumab dose.)
• Primary ocular and mucosal melanomas are allowed.
• Must be at least 28 days since treatment with chemotherapy, biochemotherapy, surgery, radiation, or immunotherapy, and recovered from any clinically significant toxicity experienced during treatment.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
• Life expectancy of ≥ 16 weeks.
• Subjects must have baseline (screening/baseline) radiographic images, (e.g. brain, chest, abdomen, pelvis, and bone scans with specific imaging tests to be determined by the attending physician) within 6 weeks of initiation of ipilimumab.
• Required values for initial laboratory tests:
• White blood cell (WBC) ≥ 2000/uL (\~ 2 x 10\^9/L)
• Absolute neutrophil count (ANC) ≥ 1000/uL (\~ 1 x 10\^9/L)
• Platelets ≥ 75 x 10\^3/uL (\~ 75 x 10\^9/L)

You may not qualify if:

• Sex and Reproductive Status
• WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study and for up to 8 weeks after the last dose of investigational product.
• WOCBP using a prohibited contraceptive method.
• Women who are pregnant or breastfeeding.
• Women with a positive pregnancy test on enrollment or before investigational product administration.
• Target Disease Exceptions
• Subjects on any other systemic therapy for cancer, including any other experimental treatment.
• A history of AEs with prior IL-2 or Interferon will not preclude subjects from entering the current study.
• Subjects who relapsed in study MDX010-16 are not eligible for this study.
• Medical History and Concurrent Diseases
• Autoimmune disease: subjects with a documented history of inflammatory bowel disease, including ulcerative colitis and Crohn's disease are excluded from this study as are subjects with a history of symptomatic disease (eg, rheumatoid arthritis, systemic progressive sclerosis \[scleroderma\]; systemic lupus erythematosus (SLE); autoimmune vasculitis \[eg, Wegener's Granulomatosis\]). Subjects with motor neuropathy considered of autoimmune origin (eg, Guillain-Barre Syndrome and Myasthenia Gravis) are excluded from this study.
• Any subject who has a life-threatening condition that requires high-dose immunosuppressant(s)
• Presence of known Hepatitis B or Hepatitis C infection, regardless of control on antiviral therapy
• Subjects with melanoma who have another active, concurrent, malignant disease are not eligible for the CA184045 study, with the exception of subjects with adequately treated basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix.
• Medical History and Concurrent Diseases

Sponsors & Collaborators

• Stanford University: lead

Study Sites (1)

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

Related Publications (1)

• Hiniker SM, Reddy SA, Maecker HT, Subrahmanyam PB, Rosenberg-Hasson Y, Swetter SM, Saha S, Shura L, Knox SJ. A Prospective Clinical Trial Combining Radiation Therapy With Systemic Immunotherapy in Metastatic Melanoma. Int J Radiat Oncol Biol Phys. 2016 Nov 1;96(3):578-88. doi: 10.1016/j.ijrobp.2016.07.005. Epub 2016 Jul 15.

  PMID: 27681753 RESULT

MeSH Terms

Conditions

Melanoma

Interventions

Ipilimumab; Radiotherapy; Radiation

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Therapeutics; Physical Phenomena

Limitations and Caveats

This study was intended to be exploratory and had a limited sample size. Our results are based on a small sample size and further research should be done to really draw firm conclusions.

Results Point of Contact

• Title: Dr. Susan J Knox
• Organization: Stanford Cancer Institute

sknox@stanford.edu

650-725-2720

Study Officials

• Susan J Knox, PhD, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Radiation Oncology

Study Record Dates

• First Submitted: October 5, 2011
• First Posted: October 10, 2011
• Study Start: October 1, 2011
• Primary Completion: December 31, 2015
• Study Completion: December 1, 2016
• Last Updated: March 2, 2020
• Results First Posted: March 10, 2017

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)