Phase II Randomized Trial of Ipilimumab Versus Ipilimumab and Radiotherapy in Metastatic Melanoma

NCT01689974 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 12-02746
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

An attractive area of research regards immune manipulations to recover some of the patient's immune response to his/her tumor, a strategy that has the advantages of being both natural and potentially long-lasting.\[1\] We propose to combine immunotherapy with radiotherapy directed to a metastatic site, to create a "hub" for in vivo immunization to the tumor, to enable "tumor rejection" at the other metastatic sites. This "in vivo immunization" is explored as a viable alternative to an individualized vaccine approach. Preclinical data generated by us and others support a "proof of principle" clinical trial that may open the field to an alternative use of radiotherapy in a novel partnership with cancer immunotherapy.\[2\]

Conditions

Metastatic Melanoma

Keywords

Metastatic Melanoma; Radiation Therapy; Immunology; Abscopal

Outcome Measures

Primary Outcomes (1)

• Response Rates of Ipilimumab Alone and of Ipilimumab With Radiation Therapy and to Estimate the Difference Between Response Rates With Ipilimumab Alone and Ipilimumab With Radiation Therapy

  Eligible patients have metastatic melanoma with at least 2 measurable sites of disease. All patients with metastatic melanoma are eligible to be randomly assigned to Ipilimumab 3mg/kg IV over 90 minutes versus Ipilimumab 3 mg/kg IV over 90 minutes and radiotherapy to one of their measurable lesions, 6 Gy X5 (conformally or by IMRT/IGRT, to maximally spare normal tissue). For patients assigned to the Ipi/RT arm, Ipilimumab treatment starts after radiotherapy, with a dose given on day 4 from the first radiotherapy fraction and repeated on Days 25, 46 and 67. Patients will be re-imaged on Week 12 and evaluated for response (defined as an objective response of another metastatic site outside the radiation field). This response will be evaluated assessing clinical and CT responses in the non-irradiated measurable metastatic sites.

  2 years

Study Arms (2)

Arm A: Ipilimumab

OTHER

Ipilimumab administered alone Day 4, 25, 46, and 67

Drug: Ipilimumab

Arm B: Ipilimumab and Radiation

OTHER

Radiation Therapy and Ipilimumab. Radiation treatment is administered for 5 fractions (sessions) over 1 week. On Day 4 treatment with Ipilimumab begins and continues on Days 25, 46, and 67.

Drug: Ipilimumab; Radiation: Radiation Therapy

Interventions

Ipilimumab DRUG

Ipilimumab will be administered alone on day 4, 25, 46 and 67.

Also known as: Yervoy

Arm A: Ipilimumab; Arm B: Ipilimumab and Radiation

Radiation Therapy RADIATION

Radiation is given over one week interval On the fourth day of radiation (day 4)Ipilimumab is administered and repeated on Days 25, 46 and 67.

Arm B: Ipilimumab and Radiation

Eligibility Criteria

• Age: 19 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability to understand and the willingness to sign a written informed consent document;
• Histologic diagnosis of locally unresectable, metastatic melanoma.
• Any BRAF status is permitted
• Any prior therapy is permitted except prior therapy with ipilimumab.
• Patients must have at least 2 distinct measurable metastatic sites, with one of at least 1 cm or larger in its largest diameter and may have additional non-measurable but established metastatic lesions (i.e. bone metastases).
• Patients must have adequate organ and marrow function as defined by initial laboratory tests:
• WBC 2000/uL
• ANC 1000/uL
• Platelets 50 x 103/uL
• Hemoglobin 8 g/dL
• Creatinine 3.0 x ULN
• AST/ALT 2.5 x ULN for patients without liver metastasis
• Bilirubin 3.0 x ULN, (except patients with Gilbert's Syndrome, who must have a total bilirubin less than 3.0 mg/dL;
• Performance status ECOG 0-1 or Karnofsky \> 50%;
• Men and women, ages \> 18 year old of age;

You may not qualify if:

• Patients having no lesions outside the field of radiation thus nullifying the ability to measure an abscopal effect;
• Autoimmune disease: Patients with a history of inflammatory bowel disease are excluded from this study as are patients with a history of symptomatic disease (e.g., rheumatoid arthritis, systemic progressive sclerosis \[scleroderma\], Systemic Lupus Erythematosus, autoimmune vasculitis \[e.g., Wegener's Granulomatosis;
• Any underlying medical or psychiatric condition, which in the opinion of the Investigator, will make the administration of study drug hazardous or obscure the interpretation of AEs, such as a condition associated with frequent diarrhea;
• Any non-oncology vaccine therapy used for prevention of infectious diseases (for up to one month prior to or after any dose of ipilimumab);
• Concomitant therapy with any of the following: IL-2, interferon or other non-study immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive agents; other investigation therapies; or chronic use of systemic corticosteroids;
• Women who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least 8 weeks after cessation of study drug, or have a positive pregnancy test at baseline, or are pregnant or breastfeeding;
• Persons of reproductive potential must agree to use and utilize an adequate method of contraception throughout treatment and for at least 8 weeks after study drug is stopped;
• Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) illness.

Sponsors & Collaborators

• NYU Langone Health: lead

Study Sites (1)

NYU Clinical Cancer Center

New York, New York, 10016, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

Ipilimumab; Radiotherapy

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

Results Point of Contact

• Title: Sylvia Formenti, MD
• Organization: New York University School of Medicine

formenti@med.cornell.edu

646.962.4073

Study Officials

• Silvia C. Formenti, M.D.

  NYULMC Department Radiation Oncology

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 18, 2012
• First Posted: September 21, 2012
• Study Start: January 1, 2013
• Primary Completion: March 1, 2015
• Study Completion: March 1, 2015
• Last Updated: February 23, 2018
• Results First Posted: February 23, 2018

Record last verified: 2018-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)