MDACC Study Summary 2004-0664

Study Summary
No. 2004-0664:.......Lung......Daniel Karp......Thoracic and Head and Neck Med

Study Summary Title



Study Summary Number:	2004-0664

Study Title:	A Phase 1B Dose Escalation/Phase 2 Randomized, Non-Comparative, Multiple Center, Open Label Study of CP-751,871 in Combination with Paclitaxel and Carboplatin and of Paclitaxel and Carboplatin Alone as First Line treatment for Advanced Non-small Cell Lung Cancer

Physician

New Patient Referral



Name:	Daniel Karp	Patients Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Dept:	Thoracic and Head and Neck Med	Referring MD Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Phone:	713-792-6363 Contact us about clinical trials

General Information



Disease Group:	Lung	Supported By:	N/A

Phase of Study:	Phase I/Phase II	Return Visit:	Day 1- C1 Day 2- C1, C4 Day 4-C1, C4 Day 8-C1, C4 Days 14-21 Day 21

Treatment Agents:	CP-751871	Home Care:	None.

Treatment Loc:	Independent Multicenter Arrangements

Estimated Length of Stay in Houston:	Weekly for C1, thereafter monthly

Description/
Intervention:

The goal of this clinical research study is to learn about the benefits, risks,
and safety of giving the new drug, CP-751,871, with the standard chemotherapy
drugs, paclitaxel and carboplatin, in the treatment of NSCLC. The goal of this
part of the study is to find the highest safe dose of CP-751,871 that can be
given with paclitaxel and carboplatin. This study will also look at how long it
takes the study drug to enter your bloodstream and how long it will stay in
your body.

Study Objectives / Outcomes

***Patients with Stage IIIB or Stage IV or recurrent non-small cell lung cancer who have received no prior chemotherapy for their disease. ***

Phase 1b

Primary:

To define the safety, tolerability, maximum tolerated (MTD) and recommended Phase 2 dose (RP2D) of CP-751,871 when given in combination with paclitaxel and carboplatin.

Secondary:

To characterize the PK of CP-751,871 in combination with paclitaxel and carboplatin.
To test for the occurrence of human anti-human antibody (HAHA) response to CP-751,871.
To monitor for any signs of efficacy of CP-751,871 when given in combination with paclitaxel and carboplatin.

Phase 1b Expansion Objectives:

Primary Objective:

To further characterize the safety and tolerability of the RP2D of CP-751, 871 in combination with paclitaxel and carboplatin.

Secondary Objective:

To further characterize the PK of the RP2D of CP-751,871 when given in combination with paclitaxel and carboplatin.
To monitor any signs of efficacy of CP-751, 871 in this setting.
To test for the occurrence of HAHA response to CP-751, 871.
To characterize the pharmacodynamics (IGF-1 accumulation) of clonal and non-clonal

CP-751,871 in combination with paclitaxel and carboplatin after multiple dosing.

Phase 2:

Primary Objectives:

To assess the efficacy of multiple doses of CP-751,871 in combination with paclitaxel and carboplatin in patients with NSCLC (all NSCLC histologies).

To assess the efficacy of CP-751,871 in combination with paclitaxel and carboplatin in

patients with NSCLC tumors of primary histology other than adenocarcinoma.

Secondary Objectives:

To assess the safety and tolerability of multiple doses of CP-751, 871 in combination with paclitaxel and carboplatin.
To further characterize the PK of clonal and non-clonal CP-75 1,871 in combination with paclitaxel and carboplatin after multiple dosing.
To test for the occurrence of HAHA response to CP-751, 871.
To explore health-related quality of life outcomes (HRQoL) in both treatment arms

Study Status Information



Study Activation / Registration Date:	09/13/2005

IRB Review and Approval Date:	10/06/2004

Study Type:	Phase Ii Or Phase I/Ii

Recruitment Status:	Closed

Projected Accrual:	Approximately 24 patients will be enrolled in the dose-escalation phase, 6-12 additional patients will be enrolled in the expansion phase and 156 response evaluable patients will be enrolled in the randomized phase. Thus, approximately 192 patients will be enrolled in the study.

Enrollment Eligibility

If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:

1) Histologically or cytologically documented Stage IIIB NSCLC with a pleural or pericardial effusion or multiple ipsilateral lung nodules, or Stage IV NSCLC, or recurrent (previous surgery and radiation allowed) disease, based on the current (TNM) classification. This includes the histologic sub-types of squamous cell, adenocarcinoma, large cell, anaplastic cell, bronchoalveolar, and NSCLC NOS. Mixed tumors will be classified according to the predominant cell type; tumors with the presence of small cell elements are ineligible. Sputum cytology is not acceptable for cell type classification.

2) (con't) For Phase 1b dose escalation only: patients with other advanced tumor types will be allowed in the study provided they are amenable to treatment with paclitaxel and carboplatin.

3) For patients other than those with NSCLC, recovery from prior treatment to Grade </= 1 is required prior to enrollment/randomization.

4) For Phase 2 only: Measurable disease defined by at least one lesion that can be accurately measured and whose size is >/= 2 cm by conventional radiologic techniques or > /= 1 cm by spiral CT scan. Baseline measurements/evaluations must be completed within 4 weeks prior to dosing. Patients with non-measurable disease may be accrued in the Phase 1b portion of the study.

5) Adequate bone marrow,hepatic,renal,& cardiac func.doc.w/in 14 days prior to enroll/rand~ANC (neutrophils&bands)>or = to1.5x10*9cells/L~Platelets>or = 100x10*9cells/L~AST/ALT<or = 5.0xULN~Total bilirubin<or =1.5xULN~Serum creatinine<or = 1.5xULN or calculated creatinine clearance>or = 60ml/min~Serum albunim>or = 2.7g/dL~12-lead ECG w/ norm.tracing or non-clinically significant changes~Ph1b only :Trans-thoracic Doppler echocardiography w/Doppler:~Mitral valve thickness<or = 4mm~Mitra valve gradient<or = mmHG~Mitra valve regurgitation<or = mild. Ph2: No history of mitral valve abnormalities

6) Age > or = 18 years

7) ECOG performance status of 0 or 1

8) Females must be either:~ not of childbearing potential (surgically sterilized or at least 2 yrs post menopausal)~ if of childbearing potential using adequate method of contraception, including at least one of the following:oral, implanted, injectable contraceptive hormones,or mechanical prod. such as intrauterine device or barrier methods (diaphram, condoms, spermicides) to prevent pregnancy or practicing abstinence or have a partner that is sterile (e.g., vasectomy).Women of childbearing potential must have a neg.serum or urine pregnancy test w/in 72 hrs prior to the start of study therapy

9) Written and voluntary informed consent

10) Adequate IV access

11) Life expectancy > or = 3 months.

Exclusion Criteria:

1) For patients with NSCLC only: Any prior chemotherapy, biologic response modifiers or investigational therapy including previous adjuvant or neoadjuvant chemotherapy.

2) Phase 2 only: Prior radiotherapy (within a week prior to first study treatment) if to the only site of measurable disease unless there is documented progression of the irradiated site

3) Phase 2 Stage III only: Primary adenocarcinoma histology including adenocarcinoma, and acinar, mucinous, papillary, solid and brochoalveolar variants. Patients with adenosquamous carcinoma are also not eligible.

4) Gastrointestinal abnormalities including active gastrointestinal bleeding, unrelated to cancer, as evidenced by hematemesis, hematochezia or melena in the past 3 months without evidence of resolution documented by endoscopy or colonoscopy.

5) Symptomatic brain metastases. Brain metastases stable for <2 weeks before dosing or requiring concurrent steroid therapy or with clinical symptoms. Clinical symptoms suggestive of new brain metastasis within 2 weeks of enrollment. If such evidence exists, new brain metastasis must be ruled out by a CT scan or MRI. Patients that develop brain metastasis during the study may have treatment interrupted to receive a course of cranial radiation and restart study treatment after a recovery period of one week.

6) A serious ucontrolled medical disorder or active infection, which would impair their ability to receive study treatment. History of HIV (screening test not required).

7) Significant active cardiac disease including: uncontrolled high blood pressure, unstable angina, uncompensated congestive heart failure, myocardial infarction within the previous 6 months, or serious cardiac ventricular arrhythmias.

8) Patients who are receiving chronic steroid therapy. Use of high dose corticosteroids (> or = 100mg of prednisone per day or > 40 mg dexamethasone per day) within 1 week prior to treatment. Previous steroid treament or low dose steroid use for the control of nausea and vomiting will be allowed. Use of antiemetics for the treament of nausea and vomiting will be allowed at the discretion of the investigator.

9) Neuropathy greater than grade 1 or evidence of unstable neurological symptoms within the past 4 weeks.

10) Concurrent use of growth hormones or growth hormone inhibitors or aminoglycoside antibiotics. Interventional use of growth factors is allowed in the case of febrile neutropenia or when severe myelosuppression is complicated by a suspected infection, if deemed necessary by the investigator. Prophylactic use of growth factors will be allowed in cases of recurrent febrile neutropenia, recurrent afebrile neutropenia with a suspected underlying infection. Prophylactic or therapeutic use of erythropoietin will be permitted. Patients will be pre-medicated prior to the use of paclitaxel.

11) Known or suspected hypersensitivity to agents that contain Cremophor (polyoxyethlated castor oil) in their formulation or mannitol. Medical contraindications to any of the pre-medications required for paclitaxel infusion.

12) A history of an active malignancy (other than NSCLC) during the last 3 years except non-melanomatous skin cancer or in situ breast or cervical cancer. Breast cancer prevention treatment with hormonal agents will be permitted.

13) Major surgical procedure within 4 weeks of study drug administration. Local radiation within 1 week of study drug administration.

14) Dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent and compliance with the requirements of this protocol.

15) Women who are pregnant or breast-feeding. WOCBP or fertile males not using an adequate method of birth control.

Links

Registration Number: NCT00147537
Study Information on Clinical Trials Registry (clinicaltrials.gov)