Study of Nivolumab Plus Chemotherapy in Patients With Advanced Cancer (NivoPlus) (NivoPlus)

A Phase Ib/II Study of Nivolumab Plus Chemotherapy in Patients With Advanced Cancer (NivoPlus)

Determine Phase 2 dose of study drug

Study Overview

• Status: Terminated
• Conditions: Pancreatic Cancer; Non Small Cell Lung Cancer; Advanced Cancer; Renal Cell Cancer; Colorectal Carcinoma; Endometrial; Uterine
• Intervention / Treatment: Drug: Temsirolimus; Drug: Irinotecan; Drug: nivolumab; Drug: Irinotecan + capecitabine

Detailed Description

Determine the recommended phase 2 dose (RP2D) of chemotherapy in combination with nivolumab in subjects with advanced cancer.

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Goodyear, Arizona, United States, 85338
      • Cancer Treatment Center of America @ Western Regional Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria for Phase Ib and II:

1. Patient at least 18 years old and has definitive histologically or cytologically confirmed metastatic solid tumor.
2. Patient has one or more metastatic tumors measurable by CT scan (or PET/CT, if patient is allergic to CT contrast media). Tumor sites that are considered measureable must not have received prior radiation therapy. For metastatic tumors not measurable by CT and/or PET/CT, there needs to be tumor measuring at least 1cm in one dimension by digital calipers on physical exam.
3. Patients can be enrolled only on one of the treatment arms on this trial.
4. The investigator will select the appropriate treatment arm for the patient with the following requirements: (a) Patients cannot have had prior progression or intolerance on the single agent chemotherapy and then enrolled on an arm with that same single agent chemotherapy plus nivolumab (b) The chemotherapy on the arm selected must be considered standard of care or its components listed in the NCCN guidelines (www.nccn.org) for that cancer type.

5. Have recovered from acute toxicities of prior treatment:

   • > 3 weeks must have elapsed since receiving any investigational agent.
   • > 2 weeks must have elapsed since receiving any radiotherapy, or ≥ 3 weeks or 5 half-lives whichever is shorter for treatment with cytotoxic or biologic agents ( ≥ 6 weeks for mitomycin or nitrosoureas). Chronic treatment with non-investigational gonadotropin-releasing hormone analogs or other hormonal or supportive care is permitted.
6. Patient has adequate biological parameters as demonstrated by the following blood counts at time of screening:
7. Absolute neutrophil count (ANC) > 1500 mm3, platelet count ≥ 100×109 L, hemoglobin ≥ 9 g/dL. Subject can be given packed red blood cell transfusion

8. Calculated creatinine clearance > 40 ml/min by Cockroft-Gault equation:

   [CreatClear = Sex * ((140 - Age) / (SerumCreat)) * (Weight / 72); where Sex = 1 for men and 0.85 for women], total bilirubin 1.5 times the upper limit of normal (ULN) range, AST/ALT ≤ 3 times the upper limit of normal (ULN) range.

9. Thyroid stimulating hormone (TSH) within institutional normal limits. If TSH is above the upper limit of normal range, then a free T4 within institutional normal limits is acceptable. If thyroid replacement therapy is initiated then patient may be screened and enrolled once the above criterion is met.
10. Persistent prior systemic therapy non-hematologic AE grade ≤ 2 (except alopecia or correctable electrolyte abnormality with supplementation)
11. Patient has a Karnofsky performance status (KPS) ≥ 70.
12. Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically sterile) must be willing to use an acceptable contraceptive method (abstinence, oral contraceptive or double barrier method) for the duration of the study and for 5 months following the last dose of nivolumab and 30 days following the last dose of chemotherapy on this trial on this trial, and must have a negative urine or serum pregnancy test within 2 weeks prior to beginning treatment on this trial. If a female subject or female partner of a male subject becomes pregnant during this period then patient will be recommended to seek appropriate obstetric care. The study will not be monitoring subjects or female partners of subjects for pregnancy after the last dose of study drug or chemotherapy.

Exclusion Criteria for Phase Ib and II:

1. Active clinically serious infection > CTCAE (version 4.03) Grade 2.
2. Serious non-healing wound, ulcer, or bone fracture.
3. Patient has known brain metastases. Baseline imaging of the brain is required within 28 days prior to randomization.
4. Prior therapy with a mammalian target of rapamycin (mTOR) inhibitor for the RCC subjects, prior therapy with irinotecan or topotecan for NSCLC subjects, and prior therapy with irinotecan for CRC patients.
5. Inability to complete informed consent process and adhere to the protocol treatment plan and follow-up requirements.
6. Patient has known active infection with HIV, hepatitis B, or hepatitis C (patients are NOT required to be tested for the presence of such viruses prior to therapy on this protocol).
7. Requiring daily corticosteroid dose ≥ 10 mg prednisone or equivalent per day.
8. Patient has undergone major surgery, other than diagnostic surgery (e.g., surgery done to obtain a biopsy for diagnosis without removal of an organ), within 4 weeks prior to Day 1 of treatment in this study.
9. Patient has serious medical risk factors involving any of the major organ systems, or serious psychiatric disorders, which could compromise the patient's safety or the study data integrity.
10. Patient will be receiving any other anti-cancer therapy during participation in this trial.
11. Prior treatment with nivolumab is not allowed. Prior receipt of other PD-1 inhibitors or PD-L1 inhibitors is allowed.
12. Active or prior documented autoimmune disease requiring systemic treatment within the past 2 years.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1; Temsirolimus 25 mg every 14 days + nivolumab	Drug: Temsirolimus; Other Names: Torisel; Drug: nivolumab; Other Names: Opdivo
Experimental: Arm 2; Irinotecan 150 mg/m2 every 14 days + nivolumab	Drug: Irinotecan; Other Names: Camptosar; Drug: nivolumab; Other Names: Opdivo
Experimental: Arm 3; Irinotecan + capecitabine + nivolumab irinotecan 175 mg/m2 on day 1 every 14 days + capecitabine 1000 mg PO BID days 1-5 on, days 6-7 off, each 7 day period	Drug: nivolumab; Other Names: Opdivo; Drug: Irinotecan + capecitabine; Other Names: Camptosar + Xeloda

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The recommended phase 2 dose (RP2D) of chemotherapy in combination with nivolumab in subjects with advanced cancer.	phase 2 dosing of nivolumab + chemotherapy	up to 4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of grade 3 or higher treatment-related adverse events by CTCAE 4.03	Identify adverse Events	up to 12 months
Response rate by irRC and response evaluation criteria in solid tumors (RECIST) 1.1 criteria1,2	Identify tumor response	12 weeks
The overall survival (OS) and progression-free survival (PFS)	Assess time until death after treatment	up to 12 months
Quantify changes in amount of blood proteins and circulating tumor DNA in patients enrolled on this study	Assess tumor marker levels	up to 12 months

Collaborators and Investigators

• Sponsor: Western Regional Medical Center
• Investigators: Study Director: Jordan Waypa, MSN, FNP, Western Regional Medical Center; Principal Investigator: Cynthia Lynch, MD, Western Regional Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2015
• Primary Completion (Actual): November 1, 2017
• Study Completion (Actual): November 1, 2017

Study Registration Dates

• First Submitted: April 13, 2015
• First Submitted That Met QC Criteria: April 21, 2015
• First Posted (Estimate): April 22, 2015

Study Record Updates

• Last Update Posted (Actual): July 2, 2018
• Last Update Submitted That Met QC Criteria: June 28, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Kidney Neoplasms; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Neoplasms; Carcinoma, Renal Cell; Colorectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Immune Checkpoint Inhibitors; Topoisomerase I Inhibitors; Capecitabine; Nivolumab; Irinotecan; Sirolimus
• Other Study ID Numbers: WG2015001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED