Temsirolimus and Bevacizumab in Treating Patients With Stage III or Stage IV Malignant Melanoma

NCT00397982 | Completed Phase 2 Results

• 8 other identifiers: NCI-2009-00133NCI-7190CDR0000512836UVACC-MEL-47MEL477190P30CA044579R21CA128367
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 2

Brief Summary

This phase II trial is studying how well giving temsirolimus together with bevacizumab works in treating patients with stage III or stage IV malignant melanoma. Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for their growth. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of malignant melanoma by blocking blood flow to the tumor. Giving temsirolimus together with bevacizumab may kill more tumor cells.

Conditions

Recurrent Melanoma; Stage IIIB Skin Melanoma; Stage IIIC Skin Melanoma; Stage IV Skin Melanoma

Outcome Measures

Primary Outcomes (1)

• Objective Tumor Response (Complete Response and Partial Response) and Progression in Participants With Stage III or IV Melanoma Following Treatment With Temsirolimus and Bevacizumab

  Evaluated using Response Evaluation Criteria In Solid Tumor (RECIST) criteria. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI and/or CT: Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for a Partial Response nor sufficient increase to qualify for Progression of Disease (POD); POD, 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Complete Response (CR), Disappearance of all target lesions.

  Up to 18 weeks after registration.

Secondary Outcomes (5)

• Adverse Events in Participants With Stage III or IV Melanoma Treated With Temsirolimus and Bevacizumab

  On days 1 and 8 of each cycle, and up to 2 years after registration.

• Association Between Expression or Activation of One Biomarker With Another, With Biochemical and Clinical Responses, With Alterations in Cell Proliferation and Apoptotic Markers, and With Time to Progression

  Day 1 of course 1 and day 8 of course 2

• Comparison of Biomarkers to Antitumor Activity/Patient Outcomes

  Day 1 of course 1 and day 8 of course 2

• Comparison of Pre- vs Post-treatment Measurements of Biomarkers and Vascular System/Immune System Parameters

  Day 1 of course 1 and day 8 of course 2

• Progression-free Survival

  Day 11 of courses 4, 8, 12, 16, 20, and 24, and then annually for up to 5 years

Study Arms (1)

Treatment (enzyme inhibitor, monoclonal antibody)

EXPERIMENTAL

Patients receive temsirolimus IV over 30 minutes on days 1 and 8 and bevacizumab IV over 30-90 minutes on day 8. Treatment repeats every 14 days for a maximum of 26 courses in the absence of disease progression or unacceptable toxicity. Patients undergo tumor resection on day 9 of course 2.

Biological: Bevacizumab; Other: Laboratory Biomarker Analysis; Drug: Temsirolimus; Procedure: Therapeutic Conventional Surgery

Interventions

Bevacizumab BIOLOGICAL

Given IV

Also known as: Anti-VEGF, Anti-VEGF Humanized Monoclonal Antibody, Anti-VEGF rhuMAb, Avastin, Bevacizumab Biosimilar BEVZ92, Bevacizumab Biosimilar BI 695502, Immunoglobulin G1 (Human-Mouse Monoclonal rhuMab-VEGF Gamma-Chain Anti-Human Vascular Endothelial Growth Factor), Disulfide With Human-Mouse Monoclonal rhuMab-VEGF Light Chain, Dimer, Recombinant Humanized Anti-VEGF Monoclonal Antibody, rhuMab-VEGF

Treatment (enzyme inhibitor, monoclonal antibody)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (enzyme inhibitor, monoclonal antibody)

Temsirolimus DRUG

Given IV

Also known as: CCI-779, CCI-779 Rapamycin Analog, Cell Cycle Inhibitor 779, Rapamycin Analog, Rapamycin Analog CCI-779, Torisel

Treatment (enzyme inhibitor, monoclonal antibody)

Therapeutic Conventional Surgery PROCEDURE

Undergo tumor resection

Treatment (enzyme inhibitor, monoclonal antibody)

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed melanoma
• Stage III or IV disease
• Recurrent disease allowed
• Measurable disease defined as ≥ 1 lesion that can be accurately measured in ≥ 1 dimension as ≥ 20 mm with conventional techniques OR ≥ 10 mm with spiral CT scan
• Tumor lesions in previously irradiated areas are not considered measurable disease
• Prior brain metastases allowed provided all of the following criteria are met:
• No more than a total of 5 brain metastases
• All metastases are no more than 2.5 cm
• Surgically resected or have been treated with gamma-knife or stereotactic radiosurgery
• More than 30 days since prior disease progression
• More than 30 days since prior steroids for managing brain metastases
• Concurrent steroids for other reasons allowed provided the dose is \< that required for managing brain metastases
• Disease accessible for core needle biopsy, incisional biopsy, and/or surgical resection and meets one of the following criteria:
• One large tumor deposit ≥ 5 cm³ from which biopsies can be harvested multiple times
• Multiple deposits that can be biopsied or excised individually on different dates, measured as follows:

You may not qualify if:

• Participants who have received these medications or treatments at any time ≤ 4 weeks of registration:
• Chemotherapy
• Radiotherapy to non-target lesions and lesions that are not to be biopsied. Prior radiotherapy to target lesions or lesions to be biopsied/resected is not permitted
• Immunotherapy
• Cytokine therapy
• Investigational reagents
• Invasive procedures defined as follows:
• Major surgical procedure, open biopsy or significant traumatic injury
• Anticipation of need for non-study related surgical procedures from registration until Cycle 26 (One year).
• Enzyme-inducing antiepileptic drugs (EIAEDs) or any other CYP3A4 inducer (Appendix C).
• OR Participants who have not recovered from adverse events resulting from the administration of these agents/procedures \> 4 weeks prior to registration.
• Participants who have received nitrosureas or mitomycin C ≤ 6 weeks of registration.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to CCI-779 or bevacizumab, or with known hypersensitivity to Chinese hamster ovary cell products (t-PA) or other recombinant human antibodies (e.g., Remicade®).
• Participants who have previously received CCI-779, rapamycin, bevacizumab, or systemic therapies targeted primarily to VEGF, VEGF receptors, or to mTOR inhibition.
• Participants who have experienced any of the following ≤ 4 weeks prior to registration:

Sponsors & Collaborators

• National Cancer Institute (NCI): lead
• Fox Chase Cancer Center: collaborator

Study Sites (2)

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

University of Virginia Cancer Center

Charlottesville, Virginia, 22908, United States

Location

Related Publications (2)

• Slingluff CL Jr, Petroni GR, Molhoek KR, Brautigan DL, Chianese-Bullock KA, Shada AL, Smolkin ME, Olson WC, Gaucher A, Chase CM, Grosh WW, Weiss GR, Wagenseller AG, Olszanski AJ, Martin L, Shea SM, Erdag G, Ram P, Gershenwald JE, Weber MJ. Clinical activity and safety of combination therapy with temsirolimus and bevacizumab for advanced melanoma: a phase II trial (CTEP 7190/Mel47). Clin Cancer Res. 2013 Jul 1;19(13):3611-20. doi: 10.1158/1078-0432.CCR-12-3919. Epub 2013 Apr 25.

  PMID: 23620404 RESULT

• Wagenseller AG, Shada A, D'Auria KM, Murphy C, Sun D, Molhoek KR, Papin JA, Dutta A, Slingluff CL Jr. MicroRNAs induced in melanoma treated with combination targeted therapy of Temsirolimus and Bevacizumab. J Transl Med. 2013 Sep 18;11:218. doi: 10.1186/1479-5876-11-218.

  PMID: 24047116 RESULT

MeSH Terms

Conditions

Melanoma

Interventions

Bevacizumab; Immunoglobulin G; Disulfides; temsirolimus; Sirolimus

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; Immunoglobulin Isotypes; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds; Organic Chemicals; Macrolides; Lactones

Results Point of Contact

• Title: Craig Slingluff
• Organization: University of Virginia

cls8h@virginia.edu

434 924 1730

Study Officials

• Craig Slingluff

  University of Virginia

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: November 9, 2006
• First Posted: November 10, 2006
• Study Start: January 1, 2008
• Primary Completion: July 1, 2013
• Study Completion: July 1, 2013
• Last Updated: June 9, 2017
• Results First Posted: June 9, 2017

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)