Temsirolimus (Torisel®) and Erlotinib (Tarceva®) in Platinum-Refractory/Ineligible, Advanced, Squamous Cell Carcinoma

NCT01009203 | Terminated Phase 2 Results DMC

• 3 other identifiers: INST OSI4641sOSI4641sNCI-2011-02948
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 2

Brief Summary

The primary hypothesis of this study is that the addition of mammalian target of rapamycin (mTOR) blockade to conventional epidermal growth factor receptor (EGFR) blockade will result in synergistic clinical activity in Squamous Cell Carcinoma of the Head and Neck (SCCHN), consistent with preclinical xenograft data. Patients will be treated with the combination of temsirolimus and erlotinib, at the previously established Maximal Tolerated Dose (MTD). The primary signal of efficacy will be progression free survival (PFS), anticipating that PFS will be prolonged compared to historical PFS in SCCHN patients treated with erlotinib or cetuximab monotherapy.

Conditions

Squamous Cell Carcinoma

Keywords

squamous cell carcinoma; head; neck; aerodigestive

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  The time from treatment initiation to disease progression or death by any cause. Progression is evaluated according to modified Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.0). Target lesions are assessed by computerized tomography (CT) or magnetic resonance imaging (MRI): Progressive Disease (PD), 20% increase in the sum of the longest diameter of target lesions, or unequivocal progression of existing non-target lesion, the appearance of new lesions, death due to disease without prior objective documentation of progression, or global deterioration in health status attributable to disease requiring a change in therapy without objective evidence of progression.

  3 years

Secondary Outcomes (3)

• Toxicity Profile

  3 years

• Overall Response Rate (ORR)

  3 years

• Overall Survival (OS)

  3 years

Study Arms (1)

Temsirolimus and Erlotinib

EXPERIMENTAL

Erlotinib (Tarceva) at 150 mg by mouth daily + Temsirolimus (Torisel) at 15 mg intravenously weekly. Each cycle is comprised of 28 days

Drug: Erlotinib; Drug: Temsirolimus

Interventions

Erlotinib DRUG

Treatment will continue until disease progression, unacceptable toxicity, or withdrawal of informed consent.

Also known as: Tarceva, OSI-774

Temsirolimus and Erlotinib

Temsirolimus DRUG

In the absence of Grade 3 or higher toxicity, a single, intra-patient dose increase of temsirolims to 20 mg intravenously weekly is permitted after the first 28 day cycle. Treatment will continue until disease progression, unacceptable toxicity, or withdrawal of informed consent.

Also known as: Torisel, CCI-779

Temsirolimus and Erlotinib

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 squamous cell carcinoma of the head and neck, from any primary site. Nasopharyngeal carcinoma, World Health Organization (WHO) Grade I, will be included.
• Advanced disease, fulfilling one of the criteria defined below:
• Incurable disease as assessed by surgical or radiation oncology
• Metastatic (M1) disease
• Persistent or progressive disease following curative-intent radiation, and not a candidate for surgical salvage due to incurability or morbidity
• Platinum-refractory or platinum-ineligible, fulfilling one of the criteria defined below:
• disease progression during or after 4-6 cycles of platinum-containing therapy in the advanced setting
• disease progression within 6 months of curative-intent treatment, which included platinum-based chemotherapy
• ineligible for platinum-containing therapy, in the opinion of the medical oncologist, due to medical comorbidities or unacceptable risk for toxicity
• patient refuses platinum-containing therapy
• Measurable disease based on response evaluation criteria in solid tumors (RECIST)
• \- disease in previously irradiated sites is considered measurable if there has been unequivocal progression of the lesion after radiotherapy, or the lesion contains residual carcinoma by biopsy more than 6 weeks after completion of radiotherapy
• Easter Cooperative Oncology Group (ECOG) performance status 0-2 at time of informed consent
• Adequate hematologic reserve and organ function
• Absolute neutrophil count \> 1200/µl

You may not qualify if:

• Nasopharyngeal primary site, if WHO grade II or III
• Prior treatment blocking the epidermal growth factor receptor (EGFR), in the advanced disease setting
• Prior treatment blocking EGFR in the curative-intent setting, if delivered in the previous 6 months
• Prior treatment with a drug blocking the mammalian target of rapamycin (mTOR)
• Sensitivity to temsirolimus or erlotinib
• Uncontrolled metastatic disease of the central nervous system
• Radiotherapy within the 2 weeks before Cycle 1' Day 1
• Surgery within the 2 weeks before Cycle 1' Day 1
• Pregnant or lactating females
• Myocardial infarction or ischemia within the 6 months preceding study treatment
• Any co morbid condition that' in the view of the attending physician' renders the patient at high risk from treatment complications
• No other concurrent, investigational anti-neoplastic agent will be permitted
• History of prior malignancy within the prior five years, with the exception of non-melanoma carcinomas of the skin, and carcinoma in situ of the cervix

Sponsors & Collaborators

• New Mexico Cancer Research Alliance: lead
• Genentech, Inc.: collaborator

Study Sites (2)

University of New Mexico Cancer Center @ Lovelace Medical Center

Albuquerque, New Mexico, 87102, United States

Location

University of New Mexico Cancer Center

Albuquerque, New Mexico, 87106, United States

Location

Related Publications (1)

• Bauman JE, Arias-Pulido H, Lee SJ, Fekrazad MH, Ozawa H, Fertig E, Howard J, Bishop J, Wang H, Olson GT, Spafford MJ, Jones DV, Chung CH. A phase II study of temsirolimus and erlotinib in patients with recurrent and/or metastatic, platinum-refractory head and neck squamous cell carcinoma. Oral Oncol. 2013 May;49(5):461-7. doi: 10.1016/j.oraloncology.2012.12.016. Epub 2013 Feb 4.

  PMID: 23384718 RESULT

MeSH Terms

Conditions

Carcinoma, Squamous Cell

Interventions

Erlotinib Hydrochloride; temsirolimus

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Julie E. Bauman, MD
• Organization: University of Pittsburgh Medical Center

baumanje@upmc.edu

4126486507

Study Officials

• Homan Fekrazad, MD

  University of New Mexico Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: November 5, 2009
• First Posted: November 6, 2009
• Study Start: December 1, 2009
• Primary Completion: September 1, 2012
• Study Completion: December 1, 2012
• Last Updated: August 10, 2015
• Results First Posted: August 10, 2015

Record last verified: 2015-07

Locations

US (2)