Tivantinib With or Without Erlotinib Hydrochloride in Treating Patients With Metastatic or Locally Advanced Kidney Cancer That Cannot Be Removed by Surgery
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| ClinicalTrials.gov Identifier: NCT01688973 |
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Recruitment Status :
Completed
First Posted : September 20, 2012
Results First Posted : January 3, 2019
Last Update Posted : January 3, 2019
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Recurrent Renal Cell Carcinoma Stage III Renal Cell Cancer Stage IV Renal Cell Cancer Type 1 Papillary Renal Cell Carcinoma Type 2 Papillary Renal Cell Carcinoma | Drug: Erlotinib Hydrochloride Other: Laboratory Biomarker Analysis Drug: Tivantinib | Phase 2 |
PRIMARY OBJECTIVES:
I. To assess the response rate (confirmed complete and partial response) of patients with locally advanced or metastatic papillary renal cell carcinoma treated with either ARQ 197 (tivantinib) or ARQ 197 combined with erlotinib (erlotinib hydrochloride).
SECONDARY OBJECTIVES:
I. To assess the progression free survival (PFS) of patients with locally advanced or metastatic papillary renal cell carcinoma treated with either ARQ 197 or ARQ 197 combined with erlotinib.
II. To assess the safety and tolerability of ARQ 197 therapy and ARQ 197 combined with erlotinib.
III. To descriptively assess the role of prior treatment on outcome.
TERTIARY OBJECTIVES:
I. To bank tissue specimens for future use and once funding is obtained to evaluate the expression of tissue correlative biomarkers such as hepatocyte growth factor receptor (c-MET) and epidermal growth factor receptor (EGFR), and to perform exploratory correlation with clinical outcomes.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive tivantinib orally (PO) twice daily (BID) on days 1-28.
ARM II: Patients receive tivantinib PO BID and erlotinib hydrochloride PO once daily (QD) on days 1-28.
In both arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 1 year and then every 6 months for up to 2 years.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 55 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Parallel (Randomized) Phase II Evaluation of ARQ 197 and ARQ 197 in Combination With Erlotinib in Papillary Renal Cell Carcinoma |
| Study Start Date : | August 20, 2012 |
| Actual Primary Completion Date : | April 30, 2017 |
| Actual Study Completion Date : | April 30, 2017 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Arm I (tivantinib)
Patients receive tivantinib PO BID on days 1-28.
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Other: Laboratory Biomarker Analysis
Correlative studies Drug: Tivantinib 360 mg (3 tablets) by mouth, Twice daily (720 mg total daily dose) on days 1-28, until disease progression |
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Experimental: Arm II (tivantinib and erlotinib hydrochloride)
Patients receive tivantinib PO BID and erlotinib hydrochloride PO QD on days 1-28.
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Drug: Erlotinib Hydrochloride
150 mg (1 tablet) by mouth on days 1-28, once daily, until disease progression Other: Laboratory Biomarker Analysis Correlative studies Drug: Tivantinib 360 mg (3 tablets) by mouth, Twice daily (720 mg total daily dose) on days 1-28, until disease progression |
- Response Rate (Confirmed Complete Response or Partial Response), Determined According to Response Evaluation Criteria in Solid Tumors [ Time Frame: Up to 3 years ]
Best Response is calculated from the sequence of objective statuses. CR: Two or more objective statuses of CR a minimum of four weeks apart documented before progression or symptomatic deterioration.
PR: Two or more objective statuses of PR or better a minimum of four weeks apart documented before progression or symptomatic deterioration, but not qualifying as CR.
Stable/no response: At least one objective status of stable/no response documented at least 6 weeks after registration and before progression or symptomatic deterioration, but not qualifying as anything else above.
Increasing disease: Objective status of progression within 12 weeks of registration, not qualifying as anything else above.
Symptomatic deterioration: Objective status of symptomatic deterioration within 12 weeks of registration, not qualifying as anything else above.
- Frequency and Severity of Toxicities, Graded by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 [ Time Frame: Up to 3 years ]This study utilized the CTCAE (NCI Common Terminology Criteria for Adverse Events) Version 4.0 for toxicity and Serious Adverse Event reporting. Patients were evaluated every two weeks for the first eight weeks and then once every four weeks. If all protocol treatment is delayed more than three weeks, patients were removed from protocol treatment
- Progression-free Survival (PFS) [ Time Frame: 30 months ]From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause. Patients last known to be alive without report of progression are censored at date of last contact.
- Number of Participants With c-MET Amplification, Deletion and No Alteration [ Time Frame: Baseline ]
- Number of Participants With EGFR Amplification, Deletion and No Alteration [ Time Frame: Baseline ]
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| Ages Eligible for Study: | Child, Adult, Older Adult |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Patients must have histologically or cytologically confirmed papillary histology renal cell carcinoma which is metastatic, or locally advanced and unresectable; mixed histologies will be allowed provided that they contain >= 50% of the papillary component
- Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension; x-rays, scans or physical examinations used for tumor measurement must have been completed within 28 days prior to registration; x-rays, scans or physical examinations for non-measurable disease must have been completed within 42 days prior to registration; all disease must be assessed and documented on the Baseline Tumor Assessment form
- Patients with metastatic disease who have a resectable primary tumor and are deemed a surgical candidate may have undergone resection; at least 28 days must have elapsed since surgery and patient must have recovered from any adverse effects of surgery
- Patients with a history of brain metastases who are asymptomatic and have not received steroid therapy in the 14 days prior to registration are eligible; anti-seizure medications are allowed provided they are non-enzyme inducing (e.g. topiramate, levetiracetam, gabapentin)
- Patients may have received up to one prior systemic therapy for advanced or metastatic renal cell carcinoma; patients must not have received a MET inhibitor or erlotinib as prior therapy; at least 21 days must have elapsed since completion of prior systemic therapy, 42 days for nitrosoureas or mitomycin C; patients must have recovered from all associated toxicities at the time of registration
- Patients may have received prior radiation therapy, but must have measurable disease outside the radiation port; at least 21 days must have elapsed since completion of prior radiation therapy; patients must have recovered from all associated toxicities at the time of registration
- Patients must not be receiving or planning to receive any other investigational agents
- Patients must have a complete physical examination and medical history within 28 days prior to registration
- Patients must have a Zubrod performance status of 0-2
- White blood cell (WBC) >= 2,000/mcL
- Absolute neutrophil count (ANC) >= 1,000/mcL
- Platelet count >= 75,000/mcL
- Serum bilirubin =< 1.5 x institutional upper limits of normal (ULN)
- Serum glutamic oxaloacetic transaminase (SGOT)/aspartate aminotransferase (AST) and serum glutamic pyruvate transaminase (SGPT)/alanine aminotransferase (ALT) must be =< 1.5 x the institutional ULN unless the liver is involved with the tumor, in which case serum transaminase (SGOT/SGPT) must be =< 5 x the institutional ULN
- Serum creatinine must be =< 2 x the institutional ULN
- Sodium, potassium and calcium must be obtained within 14 days prior to registration
- Patients with a known history of the following corneal diseases are not eligible: dry eye syndrome, Sjogren's syndrome, keratoconjunctivitis sicca, exposure keratopathy, Fuchs' dystrophy or other active disorders of cornea
- Patients known to be human immunodeficiency virus (HIV)-positive and receiving combination anti-retroviral therapy are not eligible
- Patients must be able to take oral medications; patients must not have gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for intravenous (IV) alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease; patients with intractable nausea or vomiting are not eligible
- Patients must not be pregnant or nursing; women/men of reproductive potential must have agreed to use an effective contraceptive method; a woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months; in addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation; however, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures
- No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for 5 years
- Patients must be offered the opportunity to participate in specimen banking for future translational medicine studies
- All patients must be informed of the investigational nature of this study and must sign and give written informed consent
- As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01688973
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| Principal Investigator: | Przemyslaw Twardowski | SWOG Cancer Research Network |
Documents provided by National Cancer Institute (NCI):
| Responsible Party: | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT01688973 |
| Other Study ID Numbers: |
NCI-2012-01641 NCI-2012-01641 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) S1107 SWOG-S1107 S1107 ( Other Identifier: SWOG ) S1107 ( Other Identifier: CTEP ) U10CA180888 ( U.S. NIH Grant/Contract ) U10CA032102 ( U.S. NIH Grant/Contract ) |
| First Posted: | September 20, 2012 Key Record Dates |
| Results First Posted: | January 3, 2019 |
| Last Update Posted: | January 3, 2019 |
| Last Verified: | December 2018 |
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Carcinoma Carcinoma, Renal Cell Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Adenocarcinoma Kidney Neoplasms Urologic Neoplasms Urogenital Neoplasms Neoplasms by Site Female Urogenital Diseases |
Female Urogenital Diseases and Pregnancy Complications Urogenital Diseases Kidney Diseases Urologic Diseases Male Urogenital Diseases Erlotinib Hydrochloride Antineoplastic Agents Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |