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

Squamous Cell Carcinoma Clinical Trial

Official title:

A Phase II Study of Temsirolimus (Torisel®) and Erlotinib (Tarceva®) in Platinum-Refractory or -Ineligible, Advanced, Squamous Cell Carcinoma of the Head and Neck

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01009203
• Other study ID #: INST OSI4641s
• Secondary ID: OSI4641sNCI-2011
• Status: Terminated
• Phase: Phase 2
• First received: November 5, 2009
• Last updated: July 14, 2015
• Start date: December 2009
• Est. completion date: December 2012

Study information

• Verified date: July 2015
• Source: New Mexico Cancer Care Alliance
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Description:

This is a phase II, multicenter, single arm, open-label study. Thirty-seven patients with advanced, platinum-refractory or platinum-ineligible squamous cell carcinoma of the head and neck will be sequentially enrolled to a single treatment arm. Patients will be treated with continuous, 28-day cycles of 150 mg of erlotinib by mouth daily and 15 mg of temsirolimus intervenously weekly. In the absence of grade 3 or higher toxicity in the first cycle, a single, intra-patient dose increase to 20 mg temsirolimus will be permitted.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 13
• Est. completion date: December 2012
• Est. primary completion date: September 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. 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.

2. 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

3. 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

4. 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

5. Easter Cooperative Oncology Group (ECOG) performance status 0-2 at time of informed consent

6. Adequate hematologic reserve and organ function

• Absolute neutrophil count > 1200/µl

• Platelet count > 100,000/µl

• Renal function: Serum Creatinine = 1.5x upper limit of normal (ULN)

• Liver function: Total bilirubin = 1.5x ULN, Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 2.5x ULN

7. Able to provide written, voluntary consent

8. Patients with reproductive potential must use an effective contraceptive method.

9. Male or female, age = 18 years

10. Life expectancy = 12 weeks

Exclusion Criteria:

1. Nasopharyngeal primary site, if WHO grade II or III

2. Prior treatment blocking the epidermal growth factor receptor (EGFR), in the advanced disease setting

3. Prior treatment blocking EGFR in the curative-intent setting, if delivered in the previous 6 months

4. Prior treatment with a drug blocking the mammalian target of rapamycin (mTOR)

5. Sensitivity to temsirolimus or erlotinib

6. Uncontrolled metastatic disease of the central nervous system

7. Radiotherapy within the 2 weeks before Cycle 1' Day 1

8. Surgery within the 2 weeks before Cycle 1' Day 1

9. Pregnant or lactating females

10. Myocardial infarction or ischemia within the 6 months preceding study treatment

11. Any co morbid condition that' in the view of the attending physician' renders the patient at high risk from treatment complications

12. No other concurrent, investigational anti-neoplastic agent will be permitted

13. 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

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Squamous Cell Carcinoma

Intervention

Drug:
• Erlotinib
Treatment will continue until disease progression, unacceptable toxicity, or withdrawal of informed consent.
• Temsirolimus
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.

Locations

Country	Name	City	State
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	University of New Mexico Cancer Center @ Lovelace Medical Center	Albuquerque	New Mexico

Sponsors (2)

Lead Sponsor	Collaborator
New Mexico Cancer Care Alliance	Genentech, Inc.

Country where clinical trial is conducted

United States, 

References & 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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Toxicity Profile	Toxicities (i.e. Adverse Events) are evaluated prior to each treatment and during any clinical visit. Toxicity will be evaluated per National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. The number of patients affected by adverse events of grade 3 or higher will be reported.	3 years	Yes
Secondary	Overall Response Rate (ORR)	Tumor response is evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.0). Target lesions are assessed by computerized tomography (CT) or magnetic resonance imaging (MRI:) Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions. Overall response rate (ORR) is the sum of the percentages of patients achieving complete and partial responses	3 years	No
Secondary	Overall Survival (OS)	The time from treatment initiation to death by any cause	3 years	No